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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-019952-35 | EudraCT Number |
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| Name | Class |
|---|---|
| Teva Branded Pharmaceutical Products R&D, Inc. | INDUSTRY |
| Orient Europharma Co., Ltd. | INDUSTRY |
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The purpose of this study was to determine whether LI administered in combination with cyclophosphamide, indomethacin and zinc in a multivitamin (CIZ) combination prior to standard of care therapy (surgery followed by radiotherapy or concurrent radiochemotherapy) is safe and will increase the overall survival of subjects with previously untreated locally advanced primary squamous cell carcinoma of the oral cavity or soft palate at a median of 3 to 5 years
Head and neck carcinomas constitute about 5% of all cancers annually worldwide. In the US there are about 65,000 new cases annually. Ninety percent are squamous cell carcinoma of the head and neck (SCCHN). Approximately 2/3 of SCCHN patients present on their first visit with locally advanced disease. The median 3 year overall survival (OS) for these patients with existing standard of care (SOC) therapies - surgery followed by radiotherapy or concurrent radiochemotherapy - is estimated to be between 52 and 55%; the 5 year OS is approximately 43%. There are clearly many of SCCHN patients not well served by available modalities.
Regional intra or perilymphatic and/or intratumoral or peritumoral low dose cytokine therapy may have important therapeutic effects in SCCHN patients and constitute an additional anti-tumor mechanism of action different and distinct from current SOC. Leukocyte Interleukin Injection (LI) [Multikine] contains a defined mixture of naturally derived cytokines and chemokines with demonstrated safety and immunomodulatory activity in animals and in man in Phase I and Phase II clinical trials. LI is administered prior to SOC and in combination with low non-chemotherapeutic doses of cyclophosphamide, indomethacin, and zinc (CIZ) in studies with LI. The results of these studies indicate that the local/regional injection of mixed interleukins (LI) with CIZ prior to SOC can overcome local immunosuppression, break tumor tolerance to tumor antigens and allow for a sustainable and effective anti-tumor immune response.
LI was tested in this large, global, multinational Phase III clinical trial to develop definitive proof of its efficacy and safety in treating SCCHN. The trial is an open-label randomized multi-center controlled study of LI + CIZ + SOC in subjects with advanced primary SCCHN of the oral cavity/soft palate vs. SOC [the comparator arm]. OS is the primary efficacy endpoint.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LI + CIZ + SOC | Experimental | LI plus CIZ (cyclophosphamide, indomethacin and zinc-multivitamins) was given as neoadjuvant therapy prior to standard of care (SOC). |
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| Standard of Care (SOC) only | Active Comparator | SOC for previously untreated SCCHN patients is currently surgery (with curative intent) followed by either radiotherapy or combined radiochemotherapy depending on the patient's risk status for recurrence as determined at surgery. |
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| LI + SOC | Experimental | LI was administered without CIZ to determine the contribution of CIZ to the effects of LI. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LI | Biological | LI 400 IU (2.0mL total daily) 1.0 mL peritumoral, 1.0 mL perilymphatic 5x weekly x3 consecutive weeks administered as neoadjuvant therapy prior to SOC, (surgery followed by radiation or concurrent radiochemotherapy with cisplatin 100 mg/m^2 intravenously x3) to determine if LI plus CIZ affects the 3-5 year overall survival. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | OS was assessed using Kaplan-Meier life-table using a log rank test and confirmed further with tumor stage, tumor location, and geographic stratified log rank test. Both Stratified and unstratified log rank test are presented with the unstratified log rank test constituting the primary analysis. A two-sided p-value of 0.05 or less was considered statistically significant for comparing the two groups (i.e., Study comparator arms: LI+CIZ+SOC vs. SOC alone). Interim analyses were performed (by the iDMC) periodically throughout the study to assess safety, sample size and futility. | From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months. |
| OS in Low Risk Subjects | OS was assessed using Kaplan-Meier life-table using a log rank test and confirmed further with tumor stage, tumor location, and geographic stratified log rank test. Both Stratified and unstratified log rank test are presented with the unstratified log rank test constituting the primary analysis. A two-sided p-value of 0.05 or less was considered statistically significant for comparing the two groups (i.e., Study comparator arms: LI+CIZ+SOC vs. SOC alone). Low-risk assessment and data analysis was never performed during the study and was done only after database lock. | From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Local Regional Control (LRC) | LRC is defined as the number of months from randomization to the date of documented local or regional failure (recurrence or progression) or date of last follow-up or death. LRC failure includes the reappearance (recurrence) of disease (at the original tumor sites), progressive disease (but not distant metastases), or any new disease (including new disease in lymph nodes), above the clavicle, not present at baseline. This is the traditional RTOG measure of local-regional control, also referred to as Freedom from Local Progression. |
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| Name | Affiliation | Role |
|---|---|---|
| Eyal Talor, PhD | CEL-SCI Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Simmons Cancer Institute at Southern Illinois University | Springfield | Illinois | 62794 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40191245 | Derived | Talor E, Timar J, Lavin P, Cipriano J, Markovic D, Ladanyi A, Karpenko A, Bondarenko I, Stosic S, Sobat H, Zhukavets A, Imamovic N, Chien CY, Bankowska-Wozniak M, Kisely M, Jovic R, Young JEM, Hao SP. Neoadjuvant leukocyte interleukin injection immunotherapy improves overall survival in low-risk locally advanced head and neck squamous cell carcinoma -the IT-MATTERS study. Pathol Oncol Res. 2025 Mar 21;31:1612084. doi: 10.3389/pore.2025.1612084. eCollection 2025. |
| Label | URL |
|---|---|
| Click here for more information about this study: Phase 3 Efficacy and Safety Study of Leukocyte Interleukin,Injection (LI) to Treat Cancer of the Oral Cavity (IT-MATTERS) | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | LI + CIZ + SOC | LI plus CIZ (cyclophosphamide, indomethacin and zinc) is given as adjuvant therapy prior to standard of care (SOC). |
| FG001 | Standard of Care (SOC) | SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for recurrence determined at surgery. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 27, 2014 | Mar 18, 2022 |
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| Cyclophosphamide | Drug | Cyclophosphamide was administered IV bolus (one time only) at a dose of 300mg/m^2 three days prior to beginning treatment with LI. Standard of care (SOC) for previously untreated squamous cell carcinoma of the head and neck is currently surgery followed by radiotherapy (60-70Gy in 30 to 35 fractions over 6 to 7 weeks) for higher risk subjects (subjects determined at surgery to have adverse features per the National Comprehensive Cancer Network (NCCN) guidelines, such as, positive surgical margins, 2 or more clinically positive nodes or extracapsular nodal spread, etc. that would pre-dispose them for higher risk of recurrence) radiotherapy is combined with concurrent chemotherapy (cisplatin 100mg/m^2 intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy. |
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| Indomethacin | Drug | One 25mg capsule of indomethacin was self administered orally (BID) beginning on day one of LI treatment daily until the day before surgery. |
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| Zinc | Dietary Supplement | One capsule daily self administered beginning on day one of treatment with LI until one day before surgery |
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| Surgery | Procedure | Excise tumor and nodes |
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| Cisplatin | Drug | Cisplatin was administered 100mg/m^2 IV concurrent with radiotherapy. The chemotherapy agent (cisplatin 100mg/m^2) was administered intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy. |
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| Radiotherapy | Radiation | Total 60 to 70 Gy (2Gy per day) in 30 to 35 fractions over 6 to 7 weeks to subjects determined at surgery to be at lower risk for recurrence (per NCCN guidelines). For subjects determined at surgery to be at higher risk for recurrence due to having positive surgical margins, 2 or more clinically positive nodes or extracapsular nodal spread etc. (per NCCN guidelines), radiotherapy (as above) is combined with concurrent chemotherapy (cisplatin 100 mg/m^2) intravenously on day 1 of weeks 1, 4 and 7 of radiotherapy. |
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| From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months. |
| LRC in Low Risk Subjects | LRC is defined as the number of months from randomization to the date of documented local or regional failure (recurrence or progression) or date of last follow-up or death. LRC failure includes the reappearance (recurrence) of disease (at the original tumor sites), progressive disease (but not distant metastases), or any new disease (including new disease in lymph nodes), above the clavicle, not present at baseline. This is the traditional RTOG measure of local-regional control, also referred to as Freedom from Local Progression. Low risk assessment and data analysis was never performed during the study and was done only after database lock. | From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months. |
| Progression Free Survival (PFS) | PFS is defined as the number of months from randomization to the date of first documented, progressive disease (any tumor recurrence, any new disease above clavicle or distant metastases) or the date of last follow-up or death. Progressive Disease (PD) is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions. | From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months. |
| PFS in Low Risk Subjects | PFS is defined as the number of months from randomization to the date of first documented, progressive disease (any tumor recurrence, any new disease above clavicle or distant metastases) or the date of last follow-up or death. Progressive Disease (PD) is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions. Low risk assessment and data analysis was not performed during the study and was performed only after database lock. | From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months. |
| Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 2 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 (EORTC QLQ-C30) V3.0 is composed of both multi-item scales and single-item measures. The Global Health Scale/QoL multi-item scale [GHS] is a comprised of two Items: Item 29 "How would you rate your overall health during the past week?", and item 30: "How would you rate your overall quality of life during the past week?". Both items are 7 point scales ranging from a score of 1 (very poor) to 7 (Excellent). The GHS is constructed by averaging Items 29 and 30 to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation GHS=100*[(RS-1)/6]. A higher score represents a higher ("better") QoL. Change in GHS is calculated as Observed - Baseline, so a positive change in GHS is improved QoL. Treatment comparisons are active treatment arms minus SOC, so a positive difference favors active treatment. | Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 2 |
| Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 36 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 (EORTC QLQ-C30) V3.0 is composed of both multi-item scales and single-item measures. The Global Health Scale/QoL multi-item scale [GHS] is a comprised of two Items: Item 29 "How would you rate your overall health during the past week?", and item 30: "How would you rate your overall quality of life during the past week?". Both items are 7 point scales ranging from a score of 1 (very poor) to 7 (Excellent). The GHS is constructed by averaging Items 29 and 30 to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation GHS=100*[(RS-1)/6]. A higher score represents a higher ("better") QoL. Change in GHS is calculated as Observed - Baseline, so a positive change in GHS is improved QoL. Treatment comparisons are active treatment arms minus SOC, so a positive difference favors active treatment. | Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 36 |
| EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 2 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 supplementary Head & neck cancer module (EORTC QLQ-C30 - QLQ H&N35) items 1-4 make up the symptom score for pain, items 5-8 for swallowing. The 4 pain questions score: "pain in your mouth, pain in your jaw, soreness in your mouth, a painful throat?" The 4 swallowing questions score "problems swallowing: liquids, pureed food, solid food, choking? Item are scored as 1 (Not at all) to 4 (Very much). Each symptom scale is constructed by averaging the 4 items to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation symptom score (pain or swallowing)=100*[(RS-1)/3]. A high score for these symptom scales represents a high level of symptoms.Change in symptom is calculated as Observed - Baseline, so a negative change is reduced symptomatology . Treatment comparisons are active treatment arms minus SOC, so a negative difference favors active treatment. | Baseline [pre-randomization], Long Term Follow-up Month 2 |
| EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 36 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 supplementary Head & neck cancer module (EORTC QLQ-C30 - QLQ H&N35) items 1-4 make up the symptom score for pain, items 5-8 for swallowing. The 4 pain questions score: "pain in your mouth, pain in your jaw, soreness in your mouth, a painful throat?" The 4 swallowing questions score "problems swallowing: liquids, pureed food, solid food, choking? Item are scored as 1 (Not at all) to 4 (Very much). Each symptom scale is constructed by averaging the 4 items to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation symptom score (pain or swallowing)=100*[(RS-1)/3]. A high score for these symptom scales represents a high level of symptoms.Change in symptom is calculated as Observed - Baseline, so a negative change is reduced symptomatology . Treatment comparisons are active treatment arms minus SOC, so a negative difference favors active treatment. | Baseline [pre-randomization], Long Term Follow-up Month 36 |
| Statistical Comparisons of Time-to-event Outcomes (OS, LRC, PFS) Were Repeated for Varying Levels of Histopathology (HP) Markers in Low Risk Subjects | HP analysis was performed in a blinded manner by a central pathology laboratory at the end of the study on available samples. To examine potential effects of HP markers on time-to-event efficacy outcomes (OS, LRC, PFS), participants were classified by HP marker levels: 20 HP markers were classified as (low, medium, high), 2 HP ratios as (low, medium, high) and 14 HP combinations as (low, high), resulting in 94 (20*3+2*3+2*14) possible treatment comparisons of LI + CIZ + SOC to SOC. A total of 282 (94 x 3 efficacy outcomes) statistical tests (Cox proportional hazards regressions to test for a significant treatment effect in the model) were made. Significance (two-sided p<0.05 favoring LI + CIZ + SOC) were reported under LI + CIZ + SOC. Significant test results favoring SOC were reported under SOC. The total number of statistical comparisons between LI + CIZ + SOC and SOC (282) is reported under both arms. | From the date of treatment assignment to event (LRC,PFS,OS) or the last follow-up date. Maximum follow-up was approximately 113 months. |
| Henry Ford Health System Henry Ford Hospital |
| Detroit |
| Michigan |
| 48202 |
| United States |
| University of Cincinnati Medical Center | Cincinnati | Ohio | 45219 | United States |
| Medical College Of South Carolina MSC550 | Charleston | South Carolina | 29435 | United States |
| VA Puget Sound Healthcare System & University of WA | Seattle | Washington | 98108 | United States |
| HNO-Klinik der medizinischen Universitat Graz | Graz | 8036 | Austria |
| N.N. Alexandrov Research Istitute of Oncology and Medical Radiology | Lyasny | Minsk Oblast | 223040 | Belarus |
| Vitebsk Regional Oncology Dispensary | Vitebsk | 210603 | Belarus |
| University Clinical Centre Tuzla | Trnovac | Tuzla | 75 000 | Bosnia and Herzegovina |
| Clinical Center Banja Luka | Banja Luka | 78 000 | Bosnia and Herzegovina |
| University Clinical Hospital Mostar | Mostar | 88000 | Bosnia and Herzegovina |
| Clinical Centre University of Sarejevo Clinic for ENT | Sarajevo | 71000 | Bosnia and Herzegovina |
| St. Josephs Healthcare Department of Surgery | Hamilton | Ontario | L8N4A6 | Canada |
| Centre Hospitalier Universitaire de Sherbrooke | Sherbrooke | Quebec | JiH 5N4 | Canada |
| CHU de Quebec - L'Hotel Dieu de Quebec | Québec | G1R2J6 | Canada |
| CHC Osijek | Osijek | 31000 | Croatia |
| General Hospital Dr. Josip Bencevic | Slavonski Brod | 35000 | Croatia |
| CH Dubrava | Zagreb | 10000 | Croatia |
| Clinical Hospital Center Zagreb Kispaticeva 12 | Zagreb | 10000 | Croatia |
| KBC Sestre Milosrdnice | Zagreb | 10000 | Croatia |
| KBC Zagreb | Zagreb | 10000 | Croatia |
| ICL 6 avenue Bourgogne CS30519 | Vandœuvre-lès-Nancy | 54519 | France |
| University of Debrecen Medical and Health Scioence Centre | Debrecen | Hajdú-Bihar | krt. 98 | Hungary |
| National institute of Oncology | Budapest | Rath Gyorgy | H-1122 | Hungary |
| Semmelweis University | Budapest | 1085 | Hungary |
| University of Pecs Institute of Oncotherapy | Pécs | 7628 | Hungary |
| University of Szeged Dept of Oral and Maxillofacial Surgery | Szeged | 6725 | Hungary |
| Markusovsky Teaching Hospital | Szombathely | 9700 | Hungary |
| Bibi General Hospital and Cancer Centre | Malkapet | Andhra Pradesh | 500024 | India |
| Amrita Institute of Medical Sciences | Kochi | Kerala | 682041 | India |
| Sujan Regional Cancer Hospital & Amravati Cancer Foundation | Amravati | Maharashtra | 444606 | India |
| Government Medical College and Hospital | Aurangabad | Maharashtra | 431001 | India |
| Tata Memorial Hospital | Mumbai | Maharashtra | 400012 | India |
| Curie Manavata Cancer Center | Mumbai | Naka Nashik | 422004 | India |
| Searoc Cancer Center | Jaipur | Rajashlan | 302013 | India |
| V.N. Cancer Center G. Kuppuswamy Naidu Memorial Hospital | Coimbatore | Tamil Nadu | 641037 | India |
| Meenakshi Mission Hospital and Research Centre | Madurai | Tamil Nadu | 625107 | India |
| Regional Cancer Center | Kerola | Thiruvananthapuram | 695011 | India |
| Galaxy Cancer Center | Ghaziabad | Uttar Pradesh | 210010 | India |
| Rambam Health Care Campus | Sha‘ar Ha‘Aliya | Saint Haifa | 31906 | Israel |
| Rabin Medical Center | Petah Tikva | Tikva | 49100 | Israel |
| National Tumor Institute of Italy | Naples | 80131 | Italy |
| Ospedale S.G. Moscati Santissima Annunziata | Taranto | 74010 | Italy |
| Dept of Head and Neck Surgery School of Medical Sciences Univ. Sains | Kuantan | Pulau Pinang | 16150 | Malaysia |
| University Kabangsan Medical Center | Kuala Lumpur | 56000 | Malaysia |
| Wojewodzki Szpital Specjalistyczny im Kopernika | Lodz | Ul Paderewskiego 4 | 93-509 | Poland |
| Swietokrzyskie Centrum Onkologii | Kielce | Ul. Artwinskiego 3 | 25-734 | Poland |
| Centrum Onkologi-Instytut im. Marie Sklodowskiej-Curie | Warsaw | Ul. Roentgena 5 | 02-781 | Poland |
| Centrum Onkologii im. Prof. Lukaszcyka | Warsaw | Ul. Roentgena 5 | 02-781 | Poland |
| ul. M. Sklodowskiej-Curie 24A | Bialystok | 15-276 | Poland |
| Szpital Specialistyczny im. Ludwika Rydgiera | Krakow | 31826 | Poland |
| Samodzielny Publiczny Szpital Kliniczny Klinika Otolarryngologii I Onkologii Laryngologicznej | Lublin | 20-954 | Poland |
| Weilkopolskie Centrum Onkologii Klinika Chirurgii Glowy Szye Onkologii Laryngologiczne | Poznan | 61-866 | Poland |
| Uniwersitecki Szpital Kliniczny Klinika Otolaryngologii Chirugii Glowy i Szxyi | Wroclaw | 50-556 | Poland |
| Regional Institute of Oncology IASI | Iași | 700483 | Romania |
| Spital Clinic Judetean Mures | Târgu Mureş | 540072 | Romania |
| Sverdlovsk Regional Cancer Center | Sverdlov | Ekaterinberg | 620905 | Russia |
| Leningrad Regional Oncology Center | Saint Petersburg | Leningradskaya | 188663 | Russia |
| Kursk Regional Clinical Oncology Dispensary | Kursk | 305035 | Russia |
| Blokhin Cancer Research Center | Moscow | 115478 | Russia |
| N.N. Blokhin Russian Cancer Research Center | Moscow | 115478 | Russia |
| Budget Institution of Healthcare of Omsk Region Clincal Oncology Dispensary | Omsk | 644013 | Russia |
| Ryazan Clinical oncology Dispensary | Ryazan | 39011 | Russia |
| Serbia Clinic for ENT and Maxillofacial Surgery | Belgrade | Pasterova 14 | 11000 | Serbia |
| Clincal Center Serbia Clinic for Oral and Maxillofacial Surgery | Belgrade | 11000 | Serbia |
| Faculty of Dental Medicine Clinic for Maxillofacial Surgery | Belgrade | 11000 | Serbia |
| Military Medical Academy Clinic for Maxillofacial Surgery | Belgrade | 11000 | Serbia |
| Clinical Center Nis center for Oncology | Niš | 18 000 | Serbia |
| Clinic for Stomatology department for maxillofacial Surgery | Niš | 18000 | Serbia |
| Clinical center Vojvodina Clinic for ORL | Novi Sad | 21000 | Serbia |
| Clinical Centre Vojvodina Clinic for Maxillofacial Surgery | Novi Sad | 21000 | Serbia |
| Hospital Universitari Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Universitario de Princesa | Madrid | 28006 | Spain |
| Hospital Universitario Ramon y Cajal | Madrid | 28034 | Spain |
| Hospital Madrid North Universitaro de Sanchinnaro | Madrid | 28050 | Spain |
| Complejo Hospitalario Univ. de Santiago | Santiago de Compostela | 15706 | Spain |
| Consorsio Hospital General Universitario de valencia | Valencia | 46014 | Spain |
| National Cancer Institute Dept of Clinical Oncology & Radiotherapy | Colombo | 10280 | Sri Lanka |
| Oncology Unit Teaching Hospital Karapitya | Galle | Sri Lanka |
| Kaohsiung Branch Chang Gung Memorial Hospital | Niaosong | Kaohsiung | 833 | Taiwan |
| National Cheng Kung University Hospital | Taipei | Tainan | 704 | Taiwan |
| National Taiwan Research Hospital | Chengshan | Taipei | 100 | Taiwan |
| Linkou Branch Chang Gung Memorial Hospital | Guishan | Taoyuan | 333 | Taiwan |
| Changua Christian Hospital | Chang-hua | 500 | Taiwan |
| Buddhist Tzu Chi General Hospital, Hualien Branch | Hualien City | 970 | Taiwan |
| China Medical University Hospital | Taichung | 404 | Taiwan |
| Taichung Veterans General Hospital | Taichung | 40705 | Taiwan |
| Shin-Kong Wu Ho-Su Memorial Hospital | Taipei | 111 | Taiwan |
| Khon Kaen University Dept of Otolaryngology | Nai Muang | 40002 | Thailand |
| Haceteppe University Dept of Otolaryngology - Head and Neck Surgery | Ankara | 06100 | Turkey (Türkiye) |
| Acibadem University Maslak Hospital ENT Department | Istanbul | Turkey (Türkiye) |
| Cherkasky Regional Oncological Dyspensary Dept. Head and Neck tumour | Cherkasy | 18009 | Ukraine |
| Clinical Diagnostic Laboratory of Dnepropetrovsk Municipal Institution City Multidisciplinary Clinical Hospital No. 4 | Dnipro | 49102 | Ukraine |
| Donetsk Regional Antitumor Center | Donetsk | 83092 | Ukraine |
| Grigoriev Institute for Medical Radiology of National Academy of Medical Science of Ukraine Dept. of Remote, Combined Radiation and Complex Therapy | Kharkiv | 61024 | Ukraine |
| Kharkiv Regional Clinical Oncology Center Dept. Of Head and Neck Tumour | Kharkiv | Ukraine |
| Kiev City Clinical Oncology Center of the Main Health Care Dept of Kiev Day Hospital Radiotherapy Dept. | Kiev | Ukraine |
| Kiev City Clinical Oncology Center of the Main Health Care Dept. of the Kiev Day Hospital | Kiev | Ukraine |
| Lviv State OncologyRegional treatment and Diagnostic Center | Lviv | 79031 | Ukraine |
| Sumy Regional Clinical Oncology Dyspensary | Sumy | 40004 | Ukraine |
| Zaporiz'ka Regional Clinical Oncology Dispensary | Zaporiz'ka Oblast' | 69040 | Ukraine |
| Aintree University Hospital | Liverpool | L9 7AL | United Kingdom |
| FG002 | LI + SOC | LI is administered without CIZ to determine the contribution of CIZ to the effects of LI. |
| COMPLETED |
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| NOT COMPLETED |
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Five randomized subjects were excluded due to the Crimean war (4 cases could not be followed) and one USA case where the Principal Investigator did not sign the full CRF, which left 923 ITT subjects in the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | LI + CIZ + SOC | LI plus CIZ (cyclophosphamide, indomethacin and zinc) is given as neoadjuvant therapy prior to standard of care (SOC). |
| BG001 | Standard of Care (SOC) | SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery. |
| BG002 | LI + SOC | LI is administered without CIZ to determine the contribution of CIZ to the effects of LI. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| Primary Tumor Location | Count of Participants | Participants |
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| Tumor Code | Count of Participants | Participants |
| ||||||||||||||||
| Number of Nodes Involved | Count of Participants | Participants |
| ||||||||||||||||
| TNM Stage | Staging by the American Joint Committee on Cancer (AJCC). Baseline Tumor-Node-Metastasis (TNM) Stage: Tumors that are T1-T4 by the TNM classification system are included in the study. Nodal involvement (count) must be N0-N2 and no metastatic disease (M0). TNM Stage III includes T1N1M0, T2N1M0, T3N0M0, and T3N1M0. TNM Stage IV includes all with N2 or T4 (T1N2M0, T2N2M0, T3N2M0, T4N0M0, T4N1M0, T4N2M0. Stage IV A is is associated with a poorer (worse) prognosis than Stage III. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Overall Survival (OS) | OS was assessed using Kaplan-Meier life-table using a log rank test and confirmed further with tumor stage, tumor location, and geographic stratified log rank test. Both Stratified and unstratified log rank test are presented with the unstratified log rank test constituting the primary analysis. A two-sided p-value of 0.05 or less was considered statistically significant for comparing the two groups (i.e., Study comparator arms: LI+CIZ+SOC vs. SOC alone). Interim analyses were performed (by the iDMC) periodically throughout the study to assess safety, sample size and futility. | Intent to Treat Population | Posted | Median | 95% Confidence Interval | months | From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months. |
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| Primary | OS in Low Risk Subjects | OS was assessed using Kaplan-Meier life-table using a log rank test and confirmed further with tumor stage, tumor location, and geographic stratified log rank test. Both Stratified and unstratified log rank test are presented with the unstratified log rank test constituting the primary analysis. A two-sided p-value of 0.05 or less was considered statistically significant for comparing the two groups (i.e., Study comparator arms: LI+CIZ+SOC vs. SOC alone). Low-risk assessment and data analysis was never performed during the study and was done only after database lock. | Low Risk Intent to Treat Population | Posted | Median | 95% Confidence Interval | months | From the date of treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months. |
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| Secondary | Local Regional Control (LRC) | LRC is defined as the number of months from randomization to the date of documented local or regional failure (recurrence or progression) or date of last follow-up or death. LRC failure includes the reappearance (recurrence) of disease (at the original tumor sites), progressive disease (but not distant metastases), or any new disease (including new disease in lymph nodes), above the clavicle, not present at baseline. This is the traditional RTOG measure of local-regional control, also referred to as Freedom from Local Progression. | Intent to treat population | Posted | Median | 95% Confidence Interval | months | From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months. |
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| Secondary | LRC in Low Risk Subjects | LRC is defined as the number of months from randomization to the date of documented local or regional failure (recurrence or progression) or date of last follow-up or death. LRC failure includes the reappearance (recurrence) of disease (at the original tumor sites), progressive disease (but not distant metastases), or any new disease (including new disease in lymph nodes), above the clavicle, not present at baseline. This is the traditional RTOG measure of local-regional control, also referred to as Freedom from Local Progression. Low risk assessment and data analysis was never performed during the study and was done only after database lock. | Low Risk Intent to Treat Population | Posted | Median | 95% Confidence Interval | months | From the date of treatment assignment to LRC or the last follow-up date. Maximum follow-up was approximately 113 months. |
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| Secondary | Progression Free Survival (PFS) | PFS is defined as the number of months from randomization to the date of first documented, progressive disease (any tumor recurrence, any new disease above clavicle or distant metastases) or the date of last follow-up or death. Progressive Disease (PD) is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions. | Intent to Treat Population | Posted | Median | 95% Confidence Interval | months | From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months. |
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| Secondary | PFS in Low Risk Subjects | PFS is defined as the number of months from randomization to the date of first documented, progressive disease (any tumor recurrence, any new disease above clavicle or distant metastases) or the date of last follow-up or death. Progressive Disease (PD) is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest dimension (LD) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started or the appearance of one or more new lesions. Low risk assessment and data analysis was not performed during the study and was performed only after database lock. | Low Risk Intent to treat population | Posted | Median | 95% Confidence Interval | months | From the date of treatment assignment to PFS or the last follow-up date. Maximum follow-up was approximately 113 months. |
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| Secondary | Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 2 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 (EORTC QLQ-C30) V3.0 is composed of both multi-item scales and single-item measures. The Global Health Scale/QoL multi-item scale [GHS] is a comprised of two Items: Item 29 "How would you rate your overall health during the past week?", and item 30: "How would you rate your overall quality of life during the past week?". Both items are 7 point scales ranging from a score of 1 (very poor) to 7 (Excellent). The GHS is constructed by averaging Items 29 and 30 to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation GHS=100*[(RS-1)/6]. A higher score represents a higher ("better") QoL. Change in GHS is calculated as Observed - Baseline, so a positive change in GHS is improved QoL. Treatment comparisons are active treatment arms minus SOC, so a positive difference favors active treatment. | Overall number of participants analyzed is the total number of subjects in the longitudinal model. The number of participants analyzed is the number of subjects assessed at each visit. This study is not powered for quality of life comparisons. | Posted | Least Squares Mean | Standard Error | units on a scale (0-100) | Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 2 |
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| Secondary | Quality of Life by EORTC QLQ-C30 Global Health Status [GHS] at Month 36 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 (EORTC QLQ-C30) V3.0 is composed of both multi-item scales and single-item measures. The Global Health Scale/QoL multi-item scale [GHS] is a comprised of two Items: Item 29 "How would you rate your overall health during the past week?", and item 30: "How would you rate your overall quality of life during the past week?". Both items are 7 point scales ranging from a score of 1 (very poor) to 7 (Excellent). The GHS is constructed by averaging Items 29 and 30 to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation GHS=100*[(RS-1)/6]. A higher score represents a higher ("better") QoL. Change in GHS is calculated as Observed - Baseline, so a positive change in GHS is improved QoL. Treatment comparisons are active treatment arms minus SOC, so a positive difference favors active treatment. | Overall number of participants analyzed is the total number of subjects with data at this visit. The number of participants analyzed is the number of subjects assessed at each visit. This study is not powered for quality of life comparisons. | Posted | Least Squares Mean | Standard Error | units on a scale (0-100) | Global Health Status (GHS) at Baseline [pre-randomization], Long Term Follow-up Month 36 |
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| Secondary | EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 2 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 supplementary Head & neck cancer module (EORTC QLQ-C30 - QLQ H&N35) items 1-4 make up the symptom score for pain, items 5-8 for swallowing. The 4 pain questions score: "pain in your mouth, pain in your jaw, soreness in your mouth, a painful throat?" The 4 swallowing questions score "problems swallowing: liquids, pureed food, solid food, choking? Item are scored as 1 (Not at all) to 4 (Very much). Each symptom scale is constructed by averaging the 4 items to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation symptom score (pain or swallowing)=100*[(RS-1)/3]. A high score for these symptom scales represents a high level of symptoms.Change in symptom is calculated as Observed - Baseline, so a negative change is reduced symptomatology . Treatment comparisons are active treatment arms minus SOC, so a negative difference favors active treatment. | Overall number of participants analyzed is the total number of subjects in data at that visit. The number of participants analyzed is the number of subjects assessed at each visit. This study is not powered for quality of life comparisons. | Posted | Least Squares Mean | Standard Error | units on a scale (0-100) | Baseline [pre-randomization], Long Term Follow-up Month 2 |
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| Secondary | EORTC Quality of Life Questionnaire (QLQ) - Head & Neck Cancer Module: QLQ-H&N35 at Month 36 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionaire C-30 Version 3.0 supplementary Head & neck cancer module (EORTC QLQ-C30 - QLQ H&N35) items 1-4 make up the symptom score for pain, items 5-8 for swallowing. The 4 pain questions score: "pain in your mouth, pain in your jaw, soreness in your mouth, a painful throat?" The 4 swallowing questions score "problems swallowing: liquids, pureed food, solid food, choking? Item are scored as 1 (Not at all) to 4 (Very much). Each symptom scale is constructed by averaging the 4 items to obtain a raw score (RS). The RS is then transformed to a 0-100 scale by the equation symptom score (pain or swallowing)=100*[(RS-1)/3]. A high score for these symptom scales represents a high level of symptoms.Change in symptom is calculated as Observed - Baseline, so a negative change is reduced symptomatology . Treatment comparisons are active treatment arms minus SOC, so a negative difference favors active treatment. | Overall number of participants analyzed is the total number of subjects with data at this visit. The number of participants analyzed is the number of subjects assessed at each visit. This study is not powered for quality of life comparisons. | Posted | Least Squares Mean | Standard Error | units on a scale (0-100) | Baseline [pre-randomization], Long Term Follow-up Month 36 |
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| Secondary | Statistical Comparisons of Time-to-event Outcomes (OS, LRC, PFS) Were Repeated for Varying Levels of Histopathology (HP) Markers in Low Risk Subjects | HP analysis was performed in a blinded manner by a central pathology laboratory at the end of the study on available samples. To examine potential effects of HP markers on time-to-event efficacy outcomes (OS, LRC, PFS), participants were classified by HP marker levels: 20 HP markers were classified as (low, medium, high), 2 HP ratios as (low, medium, high) and 14 HP combinations as (low, high), resulting in 94 (20*3+2*3+2*14) possible treatment comparisons of LI + CIZ + SOC to SOC. A total of 282 (94 x 3 efficacy outcomes) statistical tests (Cox proportional hazards regressions to test for a significant treatment effect in the model) were made. Significance (two-sided p<0.05 favoring LI + CIZ + SOC) were reported under LI + CIZ + SOC. Significant test results favoring SOC were reported under SOC. The total number of statistical comparisons between LI + CIZ + SOC and SOC (282) is reported under both arms. | The analysis population is the Low Risk Intent to treat Population who had HP marker levels assessed and were in either treatment arm LI + CIZ + SOC or SOC. This includes 82 subjects in LI + CIZ + SOC and 95 subjects in standard of care (SOC). No statistical comparisons were made for the 33 Low Risk subjects with HP markers in treatment arm LI + SOC. No data were collected for this Outcome Measure for treatment arm LI + SOC.. | Posted | Number | N of Statistically Significant Results | From the date of treatment assignment to event (LRC,PFS,OS) or the last follow-up date. Maximum follow-up was approximately 113 months. | Number of statistical tests | Number of statistical tests |
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| Post-Hoc | Tumor Response by RECIST 1.0 | Tumor response is evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) and confirmed by pathology at surgery. For target lesions as assessed by MRI or CT: Complete Response (CR) is disappearance of all target and non-target lesions, no new tumors, and normalization of tumor marker level. Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions taken as a reference the baseline sum of LDs, and no new tumors. Objective response = CR + PR. Response was assessed to LI treatment and compared to controls (SOC) from randomization to surgery in the ITT population for recurrence. | Intent to Treat Population | Posted | Number | participants | From treatment assignment to planned surgery, 29-38 days for LI treated groups and as soon as practicable with within 8 - 38 days for the SOC group (median 33 days). |
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| Post-Hoc | Tumor Response by RECIST 1.0 in Low Risk Subjects | Tumor response was evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). For target lesions as assessed by MRI or CT: Complete Response (CR) is disappearance of all target and non-target lesions, no new tumors, and normalization of tumor marker level. Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions taken as a reference the baseline sum of LDs, and no new tumors. Objective response = CR + PR. Response was assessed to LI treatment and compared to controls (SOC) from randomization to surgery in the lower risk ITT population for recurrence. | Low Risk Intent to Treat Population | Posted | Count of Participants | Participants | From treatment assignment to planned surgery, 29-38 days for LI treated groups and as soon as practicable with within 8 - 38 days for the SOC group (median 33 days). |
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| Post-Hoc | Survival by Objective Response (CR+PR) | Survival is assessed as dead or alive at last follow-up. Tumor response is evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). For target lesions as assessed by MRI or CT: Complete Response (CR) is disappearance of all target and non-target lesions, no new tumors, and normalization of tumor marker level. Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions taken as a reference the baseline sum of LDs, and no new tumors. Objective response = CR + PR. | Intent to Treat Population | Posted | Count of Participants | Participants | Objective Response: from treatment assignment to surgery: 29-38 days for LI-treated & 8-38 days for SOC (median 33 days). Survival from treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months. |
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| Post-Hoc | Survival by Objective Response (CR+PR) in Low Risk Subjects | OS is assessed as dead or alive at last follow-up. Tumor response is evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). For target lesions as assessed by MRI or CT: Complete Response (CR) is disappearance of all target and non-target lesions, no new tumors, and normalization of tumor marker level. Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions taken as a reference the baseline sum of LDs, and no new tumors. Objective response = CR + PR. | Low Risk Intent to Treat Population | Posted | Count of Participants | Participants | Objective Response: from treatment assignment to surgery: 29-38 days for LI-treated & 8-38 days for SOC (median 33 days). Survival from treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months. |
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| Post-Hoc | Overall Survival by Objective Response (CR+PR) in Low Risk Subjects | OS is assessed using Kaplan-Meier life-table using an unstratified log rank test and a stratified log rank test, stratified by tumor stage, tumor location, and geographic region. Alive at last follow-up was was censored. Tumor response is evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). For target lesions as assessed by MRI or CT: Complete Response (CR) is disappearance of all target and non-target lesions, no new tumors, and normalization of tumor marker level. Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions taken as a reference the baseline sum of LDs, and no new tumors. Objective response = CR + PR. | Low risk Intent to Treat Population | Posted | Number | participants | Objective Response: from treatment assignment to surgery: 29-38 days for LI-treated & 8-38 days for SOC (median 33 days). Survival from treatment assignment to death or the last follow-up date. Maximum follow-up was approximately 113 months. |
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Adverse events were reported from the signing of informed consent to the end of the study treatment follow-up. Participants were followed through 60 days after the last radio/chemoradiotherapy. Median last day of radiation-only was 122 days (IQR 106, 132 days). Median last day of chemotherapy for participants receiving both radiation and chemotherapy was 112 days (IQR 96, 129 days). Median AE follow-up was approximately six months post radiotherapy/chemoradiotherapy.
All-cause mortality reports 462 deaths in the ITT population (at risk N=923). All-cause mortality includes the 5 deaths for the 44 subjects excluded from the safety population because they were not treated in this study.
Adverse events were reported for the safety population (at risk N=879). Five (5) deaths are reported in all-cause mortality that are not reported in the adverse event module.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LI + CIZ + SOC | LI plus CIZ (cyclophosphamide, indomethacin and zinc) is given as adjuvant therapy prior to standard of care (SOC). | 204 | 395 | 216 | 383 | 354 | 383 |
| EG001 | LI + SOC | LI is administered without CIZ to determine the contribution of CIZ to the effects of LI. | 68 | 134 | 70 | 129 | 124 | 129 |
| EG002 | Standard of Care (SOC) | SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery. | 190 | 394 | 187 | 367 | 352 | 367 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Lip and/or oral cavity cancer recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Death | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Metastases to lymph nodes | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Oral cavity fistula | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Postoperative wound infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Oral cavity cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| General physical health deterioration | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Osteoradionecrosis | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Cardio-respiratory arrest | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Mucosal inflammation | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Sudden death | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Lung cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Tongue cancer recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Abscess neck | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Trismus | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Lip and/or oral cavity cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Oesophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Tongue neoplasm malignant stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Completed suicide | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Upper airway obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Cardiopulmonary failure | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Duodenal ulcer perforation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Gastric perforation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Tongue movement disturbance | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Tongue necrosis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Complication associated with device | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Osteomyelitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Peritonitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Septic shock | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Subcutaneous abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Jaw fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Post procedural complication | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Postoperative wound complication | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Radiation mucositis | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| Hypernatraemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Metastases to liver | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Metastatic neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Squamous cell carcinoma of lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Squamous cell carcinoma of the oral cavity | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Tonsil cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Delirium | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| Acute coronary syndrome | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Cardiovascular disorder | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Pericardial effusion | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Ventricular arrhythmia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Ventricular fibrillation | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Ventricular tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
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| Deafness unilateral | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
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| Blindness unilateral | Eye disorders | MedDRA 23.0 | Systematic Assessment |
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| Diplopia | Eye disorders | MedDRA 23.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Anal fistula | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Enteritis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Gastric haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Gingival bleeding | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Glossitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Incarcerated inguinal hernia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Intestinal haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Odynophagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Oesophageal compression | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oral mucosal hypertrophy | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oroantral fistula | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Small intestinal haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Submaxillary gland enlargement | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tongue disorder | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tongue oedema | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Accidental death | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Impaired healing | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Implant site ulcer | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Organ failure | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Sudden cardiac death | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Chronic hepatic failure | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Hepatitis B | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Ludwig angina | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Lung abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Lymph gland infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Oral infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Osteomyelitis acute | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Periorbital cellulitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pseudomonas infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pulmonary mycosis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Rectal abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Sepsis syndrome | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Streptococcal sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Wound abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Flap necrosis | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Postoperative adhesion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Scar | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Seroma | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Skin flap necrosis | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Skin graft contracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Oxygen saturation decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypophagia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Muscle contracture | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Adenoma benign | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Colon cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Epiglottic cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Hepatic cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Laryngeal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Lip and/or oral cavity cancer stage IV | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Metastases to salivary gland | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Nasal cavity cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Nasal sinus cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Non-small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Oesophageal squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Second primary malignancy | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of the hypopharynx | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Tongue cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Tracheal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Cerebral infarction | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cranial nerve palsies multiple | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Azotaemia | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Acute pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Obstructive airways disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oropharyngeal swelling | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arterial haemorrhage | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Lymphorrhoea | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Peripheral artery thrombosis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Venous thrombosis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Incision site pain | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Radiation injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Radiation mucositis | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Scar pain | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
See Clinical Protocol Section 13.0 Publication Plan
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Cipriano, Senior VP Regulatory Affairs, Eyal Talor Chief Scientific Officer | CEL-SCI Corporation | (205) 586-6947 | jcipriano@cel-sci.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: SAP main text | Nov 27, 2020 | Mar 18, 2022 | SAP_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: CS001P3 Note to File 1 | Dec 28, 2020 | Jun 13, 2022 | SAP_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: CS001P3 Note to file 2 | Jan 12, 2021 | Jun 13, 2022 | SAP_003.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Note to file 3 | Mar 28, 2021 | Jun 13, 2022 | SAP_004.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Note to file 4 | Mar 30, 2021 | Jun 13, 2022 | SAP_005.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Note to file 5 | Apr 29, 2021 | Jun 13, 2022 | SAP_006.pdf |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| ID | Term |
|---|---|
| D007267 | Injections |
| D003520 | Cyclophosphamide |
| D007213 | Indomethacin |
| D015032 | Zinc |
| C067316 | Geritol |
| D013514 | Surgical Procedures, Operative |
| D002945 | Cisplatin |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D028561 | Transition Elements |
| D008670 | Metals |
| D017606 | Chlorine Compounds |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Philippines |
|
| Taiwan |
|
| Thailand |
|
| India |
|
| Israel |
|
| Sri Lanka |
|
| Bosnia and Herzegovina |
|
| Serbia |
|
| Turkey |
|
| Belarus |
|
| Russia |
|
| Ukraine |
|
| Canada |
|
| Croatia |
|
| France |
|
| Hungary |
|
| Poland |
|
| Romania |
|
| United States |
|
| Floor of Mouth |
|
| Oral Tongue |
|
| Soft Palate |
|
| T2: Tumor > 2 and < 4 cm in greatest dimension or extension to lingual surface of epiglottis |
|
| T3: Tumor more than 4 cm in greatest dimension |
|
| T4a: Moderately advanced local disease |
|
| N0 |
|
| N1 |
|
| N2 |
|
| TNM Stage IV |
|
| Log Rank | This Log Rank statistic is based on a stratified analysis. | 0.5402 | Superiority |
| Regression, Cox | The Cox Proportional Hazards Model included terms for treatment, tumor stage, tumor location, and geographic region. | 0.4128 | Hazard Ratio (HR) | 1.09 | 2-Sided | 95 | 0.89 | 1.32 | A Hazard Ratio < 1.0 would favor LI + CIZ + SOC. | Superiority |
| Log Rank | This Log Rank statistic is based on an unstratified analysis. | 0.7181 | Superiority |
| Log Rank | This log Rank p-value is based on a stratified analysis. | 0.9480 | Superiority |
| Regression, Cox | The Cox Proportional Hazards Model included terms for treatment, tumor stage, tumor location, and geographic region. | 0.6101 | Hazard Ratio (HR) | 1.07 | 2-Sided | 95 | 0.81 | 1.42 | A hazard Ratio < 1.0 would favor LI + SOC. | Superiority |
|
|
|
|
|
|
|
|
|
|
|
|
SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy.
|
|
|
| LI + SOC |
LI is administered without CIZ to determine the contribution of CIZ to the effects of LI. |
| OG002 | Standard of Care (SOC) | SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery. |
|
|
|
| LI + SOC |
LI is administered without CIZ to determine the contribution of CIZ to the effects of LI. |
| OG002 | Standard of Care (SOC) | SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery. |
|
|
|
| OG001 |
| LI + SOC |
LI was administered without CIZ to determine the contribution of CIZ to the effects of LI. |
| OG002 | Standard of Care (SOC) | SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery. |
|
|
|
| OG001 |
| LI + SOC |
LI was administered without CIZ to determine the contribution of CIZ to the effects of LI. |
| OG002 | Standard of Care (SOC) | SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery. |
|
|
|
LI plus CIZ (cyclophosphamide, indomethacin and zinc) is given as neoadjuvant therapy prior to standard of care (SOC). |
| OG001 | Standard of Care (SOC) | SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery. |
|
|
|
SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery.
|
|
|
SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery.
|
|
|
|
|
|
SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery.
|
|
|
| Standard of Care (SOC) |
SOC for previously untreated SCCHN patients is currently surgery followed by either radiotherapy or combined radiochemotherapy depending the patient's risk status for relapse determined at surgery. |
|
|
|