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Phase II, single-arm, open-label multicenter study that assesses feasibility, safety and efficacy of combined neoadjuvant chemotherapy and immunotherapy with Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months.
Phase II, single-arm, open-label multicenter study that assesses feasibility, safety and efficacy of combined neoadjuvant chemotherapy and immunotherapy with Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months.
Three cycles of neoadjuvant chemotherapy in combination with nivolumab will be administered.
After completion of neoadjuvant therapy (3 cycles) and before surgery, a tumor assessment will be done. Patients have to leave the study if there is evidence of progression. Patients with in-stable disease or partial response may be considered for surgery.
The report imaging response vs pathological response rate will be evaluated.
Patients eligible for the trial are those with a histological diagnosis or cytologically proven operable and resectable non-small-cell lung cancer. The total number of patients to be included will be 46 from 23 participating sites in Spain.
Accrual period of 1.5 years or until the inclusion of the last patient necessary to achieve the sample set in the protocol of 46 patients. After that all patients will be treated for 1 year with adjuvant immunotherapy and they will be followed during 3 years after adjuvant treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nivolumab 360 mg | Drug | Nivolumab 360 mg IV Q3W + Followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival | The progression free survival is the percentage of the patients without disease progression | at 24 months from the first dose of neoadjuvant treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Percentage of patients are still alive | at 3 years from the first dose of neoadjuvant treatment |
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Inclusion Criteria:
1. 72 x serum creatinine in mg/dL
b. Male CrCl = (140 - age in years) x weight in kg x 1.00
72 x serum creatinine in mg/dL vi. AST/ALT ⤠3 x ULN vii. Total Bilirubin ⤠1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) viii. INR/APTT within normal limits
5. The patients need to have a forced expiratory volume (FEV1) ā„ 1.2 liters
6. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and nacional guidelines, including the Declaration of Helsinki prior to any trial-related intervention.
7. Patients aged > 18 years
8. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception.
9. Women must not be breastfeeding
10. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mariano Provencio, MD | spanish Lun Cancer Group | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Complejo hospitalario de la coruƱa | A CoruƱa | CoruƱa | 15006 | Spain | ||
| Hospital Reina SofĆa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35576508 | Result | Provencio M, Serna-Blasco R, Nadal E, Insa A, Garcia-Campelo MR, Casal Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Calvo V, Martin-Lopez J, Garcia-Garcia F, Casarrubios M, Franco F, Sanchez-Herrero E, Massuti B, Cruz-Bermudez A, Romero A. Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non-Small-Cell Lung Cancer (NADIM phase II trial). J Clin Oncol. 2022 Sep 1;40(25):2924-2933. doi: 10.1200/JCO.21.02660. Epub 2022 May 16. | |
| 32979984 |
| Label | URL |
|---|---|
| Web page of the sponsor where users can find more information about SLCG studies | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 | Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months Nivolumab 360 mg: Nivolumab 360 mg IV Q3W + Followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months Paclitaxel 200mg/m2: Paclitaxel 200mg/m2 IV Q3W Carboplatin AUC 6: Carboplatin AUC 6 IV Q3W |
| 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_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 8, 2022 |
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|
| Paclitaxel 200mg/m2 | Drug | Paclitaxel 200mg/m2 IV Q3W |
|
|
| Carboplatin AUC 6 | Drug | Carboplatin AUC 6 IV Q3W |
|
|
| Córdoba |
| Córdoba |
| 14004 |
| Spain |
| Hospital Insular de Gran Canaria | Las Palmas de Gran Canaria | Gran Canaria | 35016 | Spain |
| Hospital Puerta de Hierro | Majadahonda | Madrid | 28222 | Spain |
| ClĆnica Universitaria de Navarra | Pamplona | Navarre | 31008 | Spain |
| Complejo Hospitalario de Vigo | Vigo | Pontevedra | 36212 | Spain |
| Hospital de Cruces | Bilbao | Vizcaya | 48903 | Spain |
| Hospital General de Alicante | Alicante | 03010 | Spain |
| Hospital Universitari Quirón Dexeus | Barcelona | 08028 | Spain |
| Hospital Universitari Vall Hebrón | Barcelona | 08035 | Spain |
| Hospital ClĆnic de Barcelona | Barcelona | 08036 | Spain |
| Hospital de La Santa Creu I Sant Pau | Barcelona | 08041 | Spain |
| H. Duran i Reynals-ICO | Barcelona | 08907 | Spain |
| H. de la Princesa | Madrid | 28006 | Spain |
| Hospital ClĆnico San Carlos | Madrid | 28040 | Spain |
| Hospital Fundación JimĆ©nez DĆaz | Madrid | 28040 | Spain |
| H. La Paz | Madrid | Spain |
| Hospital Son Espases | Palma de Mallorca | 07010 | Spain |
| Hospital Clinico de Salamanca | Salamanca | 37007 | Spain |
| Hospital Virgen de La Macrena | Seville | 41009 | Spain |
| Hospital Virgen Del RocĆo | Seville | 41013 | Spain |
| Hospital ClĆnico Universitario de Valencia | Valencia | 46010 | Spain |
| H. Gen. Univ. Valencia | Valencia | Spain |
| Hospital La Fe | Valencia | Spain |
| Result |
| Provencio M, Nadal E, Insa A, Garcia-Campelo MR, Casal-Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Pereira E, Royuela A, Casarrubios M, Salas Anton C, Parra ER, Wistuba I, Calvo V, Laza-Briviesca R, Romero A, Massuti B, Cruz-Bermudez A. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Nov;21(11):1413-1422. doi: 10.1016/S1470-2045(20)30453-8. Epub 2020 Sep 24. |
| 39419061 | Derived | Provencio M, Nadal E, Insa A, Garcia Campelo R, Casal J, Domine M, Massuti B, Majem M, Rodriguez-Abreu D, Martinez-Marti A, de Castro J, Gomez de Antonio D, Macia I, Figueroa S, Fernandez Vago L, Calvo V, Palmero R, Sierra-Rodero B, Martinez-Toledo C, Molina-Alejandre M, Serna-Blasco R, Romero A, Cruz-Bermudez A. Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2024 Nov;25(11):1453-1464. doi: 10.1016/S1470-2045(24)00498-4. Epub 2024 Oct 14. |
| 34446577 | Derived | Sierra-Rodero B, Cruz-Bermudez A, Nadal E, Garitaonaindia Y, Insa A, Mosquera J, Casal-Rubio J, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Massuti B, Laza-Briviesca R, Casarrubios M, Garcia-Grande A, Romero A, Franco F, Provencio M. Clinical and molecular parameters associated to pneumonitis development in non-small-cell lung cancer patients receiving chemoimmunotherapy from NADIM trial. J Immunother Cancer. 2021 Aug;9(8):e002804. doi: 10.1136/jitc-2021-002804. |
| 34376534 | Derived | Casarrubios M, Cruz-Bermudez A, Nadal E, Insa A, Garcia Campelo MDR, Lazaro M, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, de Castro-Carpeno J, Cobo M, Lopez-Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Massuti B, Barquin M, Laza-Briviesca R, Sierra-Rodero B, Parra ER, Sanchez-Espiridion B, Rocha P, Kadara H, Wistuba II, Romero A, Calvo V, Provencio M. Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy. Clin Cancer Res. 2021 Nov 1;27(21):5878-5890. doi: 10.1158/1078-0432.CCR-21-1200. Epub 2021 Aug 10. |
| 34323406 | Derived | Laza-Briviesca R, Cruz-Bermudez A, Nadal E, Insa A, Garcia-Campelo MDR, Huidobro G, Domine M, Majem M, Rodriguez-Abreu D, Martinez-Marti A, De Castro Carpeno J, Cobo M, Lopez Vivanco G, Del Barco E, Bernabe Caro R, Vinolas N, Barneto Aranda I, Viteri S, Massuti B, Casarrubios M, Sierra-Rodero B, Tarin C, Garcia-Grande A, Haymaker C, Wistuba II, Romero A, Franco F, Provencio M. Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial. Clin Transl Med. 2021 Jul;11(7):e491. doi: 10.1002/ctm2.491. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1 | Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months Nivolumab 360 mg: Nivolumab 360 mg IV Q3W + Followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months Paclitaxel 200mg/m2: Paclitaxel 200mg/m2 IV Q3W Carboplatin AUC 6: Carboplatin AUC 6 IV Q3W |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| ECOG Performance Status Scale | ECOG Performance Status Scale: It describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability GRADES: ECOG 0: Fully active. ECOG 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature ECOG 2: Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours ECOG 3: Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours ECOG 4: Completely disabled ECOG 5: Dead | Count of Participants | Participants |
| |||||||||||||||||
| Cigarette Smoking History | Count of Participants | Participants |
| ||||||||||||||||||
| Histology | Count of Participants | Participants |
| ||||||||||||||||||
| Tumor node, metastasis staging classification | 8th ed.TNM for Lung Cancer Primary tumor (T) T0 means there is no evidence of a tumor T1-T4 describe the size & location of the tumor on a scale of 1 to 4. A larger tumor or a tumor that has grown deeper into nearby tissue will get a higher number Distant metastasis (M) M0:Cancer has not spread to other parts of the body M1:Cancer has spread to other parts of the body Regional lymph nodes (N) N1: Metastasis in ipsilateral peribronchial or ipsilateral hilar lymph & intrapulmonary nodes N2:Metastasis in ipsilateral mediastinal or subcarinal lymph node N3:Metastasis in contralateral node | Count of Participants | Participants |
|
| 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 | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression Free Survival | The progression free survival is the percentage of the patients without disease progression | Posted | Number | 95% Confidence Interval | percentage of participants | at 24 months from the first dose of neoadjuvant treatment |
|
|
| ||||||||||||||||||||||||||
| Secondary | Overall Survival | Percentage of patients are still alive | Posted | Number | 95% Confidence Interval | percentage of participants | at 3 years from the first dose of neoadjuvant treatment |
|
|
40 months
The severity of AE will be determined using CTCAE version 4.0
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1 | Nivolumab 360 mg IV Q3W + Paclitaxel 200mg/m2 + Carboplatin AUC 6 IV Q3W in resectable stage IIIA N2-NSCLC adult patients followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months Nivolumab 360 mg: Nivolumab 360 mg IV Q3W + Followed by adjuvant treatment for 1 year with Nivolumab 240 mg IV Q2W for 4 months and Nivolumab 480mg Q4W for 8 months Paclitaxel 200mg/m2: Paclitaxel 200mg/m2 IV Q3W Carboplatin AUC 6: Carboplatin AUC 6 IV Q3W | 1 | 46 | 3 | 46 | 43 | 46 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 12.1 | Non-systematic Assessment |
| |
| Increased lipase | Blood and lymphatic system disorders | 12.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia or fatigue | General disorders | 12.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | 12.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | 12.1 | Non-systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | 12.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | 12.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | 12.1 | Non-systematic Assessment |
| |
| Skin disorders (rash) | Skin and subcutaneous tissue disorders | 12.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | 12.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | 12.1 | Non-systematic Assessment |
| |
| Decreased appetite or anorexia | General disorders | 12.1 | Non-systematic Assessment |
| |
| Constipation | General disorders | 12.1 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | 12.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | 12.1 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | 12.1 | Non-systematic Assessment |
| |
| Increased aminotransferases | Blood and lymphatic system disorders | 12.1 | Non-systematic Assessment |
| |
| Increased serum amylase | Blood and lymphatic system disorders | 12.1 | Non-systematic Assessment |
| |
| Increased creatinine level | Blood and lymphatic system disorders | 12.1 | Non-systematic Assessment |
| |
| Increased lipase | Blood and lymphatic system disorders | 12.1 | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eva Pereira | Fundación GECP | +34934302006 | gecp@gecp.org |
| Nov 26, 2024 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| D017239 | Paclitaxel |
| D016190 | Carboplatin |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D056831 | Coordination Complexes |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| ECOG 2 |
|
| ECOG 3 |
|
| ECOG 4 |
|
| ECOG 5 |
|
| Never smoker |
|
| NOS/Undifferenciated |
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| T2N2M0 |
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| T3N1M0 |
|
| T3N2M0 |
|
| T4N0M0 |
|
| T1N1M0 |
|
|