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Primary objective: to assess the antitumor activity and safety profile of cetuximab when given in combination with radiotherapy (RT) for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in Chinese subjects.
Secondary objective: to assess the pharmacokinetic (PK) profile and immunogenicity of cetuximab in Chinese subjects.
Further objective: to identify for cetuximab potential predictive biomarkers of response and safety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cetuximab | Experimental | All eligible subjects will receive cetuximab treatment only during week 1 of the treatment course and concomitant cetuximab and boost radiotherapy (RT) during week two to week seven of the treatment course |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cetuximab + concomitant boost radiotherapy | Biological | Cetuximab 400 milligram/square meter (mg/m^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially
|
| Measure | Description | Time Frame |
|---|---|---|
| Best Overall Response (BOR) | Best overall (objective) response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to modified World Health Organization (WHO) criteria confirmed at a repeat assessment performed no less than 28 days after the criteria for response were first met. CR was defined as disappearance of all index lesions. PR was defined as a 50% or more decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of PD. | Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 3 months following the 8 weeks after the end of RT visit until the end of trial (EOT) visit |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) | Progression-free survival was defined as the duration (in months) from first administration of trial treatment to first observation of PD (radiological or clinical, if radiological PD is not available), or death due to any cause. The PFS time of participants without observation of PD but death occurring after two or more missed consecutive tumor assessments (i.e. two-fold scheduled time interval of two consecutive tumor assessments) was censored on the date of last tumor assessment or first administration of trial treatment (whichever was later). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Li Gao | Radiotherapy Department, Cancer Institute & Hospital, Chinese Academy of Medical Science, Beijing, China | Principal Investigator |
| Junliang Cai | Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd., an Affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Guozhen Xu | Radiotherapy Department, Cancer Institute & Hospital, Chinese Academy of Medical Science, Beijing, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fujian Provincial Tumor Hospital | Fuzhou | Fujian | China | |||
| Cancer Institute and Hospital, Chinese Academy of Medical Sciences |
A total of 70 participants were screened, out of which 4 participants were not treated and 66 participants received the study treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cetuximab | Participants received cetuximab 400 milligram/square meter (mg/m^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
|
| Baseline up to disease progression or withdrawal or 12 weeks after the last radiotherapy of the last participant |
| Beijing |
| China |
| Xiangya Hospital of Central South University | Changsha, Hunan | China |
| Sun Yat-sen University Cancer Center | Guangzhou | China |
| Zhejiang Provincial Cancer Hospital | Hangzhou | China |
| Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine | Shanghai | China |
| Union Hospital of Tongji Medical College, Huazhong University of Science and Technology | Wuhan, Hubei | China |
| Zhongnan Hospital of Wuhan University | Wuhan, Hubei | China |
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cetuximab | Participants received cetuximab 400 milligram/square meter (mg/m^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy (RT): 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Age, Customized | Number | participants |
| |||||||||||||||||||||||
| Sex: Female, Male | 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 | Best Overall Response (BOR) | Best overall (objective) response was defined as the occurrence of complete response (CR) or partial response (PR) based on the investigator's assessment according to modified World Health Organization (WHO) criteria confirmed at a repeat assessment performed no less than 28 days after the criteria for response were first met. CR was defined as disappearance of all index lesions. PR was defined as a 50% or more decrease in the sum of the products of diameters (SOPD) of index lesions compared to the baseline SOPD, with no evidence of PD. | Intention-to-treat (ITT) population included all participants who received at least one dose of the investigational medicinal product (IMP) cetuximab or RT. | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 3 months following the 8 weeks after the end of RT visit until the end of trial (EOT) visit |
|
|
| |||||||||||||||||||||||||
| Secondary | Progression-Free Survival (PFS) | Progression-free survival was defined as the duration (in months) from first administration of trial treatment to first observation of PD (radiological or clinical, if radiological PD is not available), or death due to any cause. The PFS time of participants without observation of PD but death occurring after two or more missed consecutive tumor assessments (i.e. two-fold scheduled time interval of two consecutive tumor assessments) was censored on the date of last tumor assessment or first administration of trial treatment (whichever was later). | ITT population included all participants who received at least one dose of the IMP cetuximab or RT. | Posted | Median | 95% Confidence Interval | months | Baseline up to disease progression or withdrawal or 12 weeks after the last radiotherapy of the last participant |
|
Up to Day 60 after last trial treatment administration and before EOT
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
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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 | Cetuximab: Treatment Emergent Phase | Participants received cetuximab 400 milligram/square meter (mg/m^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. Treatment emergent phase, i.e. treatment-emergent adverse events (TEAEs, adverse events which occur or worsen on the first dosing day of trial treatment and until 60 days after the last trial treatment administration (cetuximab or radiotherapy). | 5 | 66 | 64 | 66 | ||
| EG001 | Cetuximab: Late Phase | Participants received cetuximab 400 milligram/square meter (mg/m^2) intravenous (IV) infusion over 120 minutes for 1 week, subsequently followed by 250 mg/m^2 IV infusion over 60 minutes, from week 2 to 7 along with concomitant boost radiotherapy: 72.0 Gray (Gy) total for 42 fractions in 6 weeks, initially, once-daily fractions: 32.4 Gy in 18 fractions of 1.8 Gy for 3.6 weeks (5 fractions/week), followed by twice-daily fractions 39.6 Gy in 24 fractions for 2.4 weeks: morning dose 1.8 Gy/fraction for a total of 12 fractions 5 fractions/week; evening dose 1.5 Gy/fraction for a total of 12 fractions 5 fractions/week. Doses were separated by at least a 6-hour interval. Late phase, i.e. adverse events which occur or worsen more than 60 days after the last trial treatment administration (cetuximab or radiotherapy), and before end of trial. | 14 | 62 | 20 | 62 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron deficiency anemia | Blood and lymphatic system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hematemesis | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Localized edema | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Tracheal obstruction | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Esophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (13.0) | Systematic Assessment |
| |
| Paresthesia | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Asphyxia | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Laryngeal edema | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pharyngeal hemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hemorrhage | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Salivary gland pain | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Tongue exfoliation | Gastrointestinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Infusion related reaction | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Furuncle | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Herpes simplex | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Parotitis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Rubella | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Urethritis | Infections and infestations | MedDRA (13.0) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Radiation mucositis | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Radiation myelopathy | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA (13.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA (13.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Haemorrhage urinary tract | Renal and urinary disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Genital pain | Reproductive system and breast disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Increased bronchial secretion | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Increased upper airway secretion | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pharyngeal haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Pharyngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Exfoliative rash | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Skin chapped | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (13.0) | Systematic Assessment |
|
All submissions by the PI for publication require the written permission from the sponsor. The PI commits to forward to the sponsor all documents intended for publication which contains data or results generated in connection with the study. Documents must be available at least 60 days before the planned submission date to allow for review. Any publication should follow the policy in the protocol. The PI shall not publish results derived from the study until the study has been reported in full.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Responsible | Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd. | +49-6151-72-5200 | service@merckgroup.com |
| 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 |
|---|---|
| D000068818 | Cetuximab |
| 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 |
Not provided
Not provided
| Units | Counts |
|---|---|
| Participants |
|
|