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This study is conducted in Japanese newly diagnosed locally advanced SCCHN patients in order to assess tolerability and feasibility of Cetuximab plus concomitant boost radiotherapy (RT) regimen (the study treatment) and its safety profile (i.e. AEs: adverse events). In addition, efficacy (i.e. anti-tumor effect) of the study treatment is also evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cetuximab With Radiotherapy | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cetuximab | Drug | Patients receive Cetuximab at an initial dose of 400 mg/m^2 of Cetuximab to be infused 6 or 7 days before starting radiotherapy, followed by subsequent weekly infusions at a dose of 250 mg/m^2 of Cetuximab and RT (72.0 Gy total in 42 fractions) for the next 6 weeks of the treatment course. Subjects will receive Cetuximab until radiographically documented progressive disease or unacceptable toxicity occurs or consent is withdrawn. If RT is delayed, administration of Cetuximab every 7 days is continued. If RT is discontinued for any reason, treatment with Cetuximab monotherapy every 7 days is continued. |
| Measure | Description | Time Frame |
|---|---|---|
| Completion Rate | Number of subjects who complete ≥70% of Cetuximab planned dose administration in terms of relative dose intensity of Cetuximab and full dose of RT ≤2 weeks over planned schedule in terms of RT duration ≤8 weeks, divided by the the number of subjects in the ITT/Safety population | time from first administration of cetuximab to last administration of cetuximab or RT (whichever is later), ≤ 9 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Best Response Rate | Number of subjects experiencing a Complete Response (complete disappearance of measurable and evaluable disease without new lesions) or Partial Response (>=50% decrease of the sum of the product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions) at 8 weeks post radiotherapy (confirmed by repeat assessment at week 12) based on imaging according to modified World Health Organisation criteria as assessed independently by the Efficacy and Safety Evaluation Committee, divided by the number of subjects in the ITT/safety population |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Masataka Ota, MD | Merck Serono Co.,Ltd, an Affilate of Merck Serono, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Aichi | Japan | ||||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23479383 | Result | Okano S, Yoshino T, Fujii M, Onozawa Y, Kodaira T, Fujii H, Akimoto T, Ishikura S, Oguchi M, Zenda S, de Blas B, Tahara M, Beier F. Phase II study of cetuximab plus concomitant boost radiotherapy in Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Jpn J Clin Oncol. 2013 May;43(5):476-82. doi: 10.1093/jjco/hyt030. Epub 2013 Mar 10. |
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27 subjects were enrolled and 5 were ineligible, not treated, and excluded from the Intention To Treat (ITT)/Safety Population. Reasons: investigator's decision (1 subject), withdrawal of consent (1 subject), inability to perform radiation therapy according to protocol (2 subjects) and inclusion/exclusion criteria not fulfilled (1 subject).
Subjects were enrolled in this study at 4 centers in Japan. The first subject was enrolled on 06 March 2009 and the last on 04 January 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cetuximab With Radiotherapy | Subjects received cetuximab at an initial dose of 400 mg/m² infused 6 or 7 days before starting radiotherapy (RT). This was followed by subsequent weekly infusions of 250 mg/m² cetuximab administered in combination with radiotherapy (5 days/week) for 6 weeks. Subjects will receive cetuximab until radiographically documented progressive disease or unacceptable toxicity occurs or consent is withdrawn. If RT is delayed, administration of cetuximab every 7 days is continued. If RT is discontinued for any reason, treatment with cetuximab monotherapy every 7 days is continued. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| best response was determined at week 8 post radiotherapy, for subjects with complete or partial response a confirmation in week 12 post radiotherapy was required |
| Safety - Number of Patients Experiencing Any Adverse Event | Please refer to Adverse Events section for further details | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks |
| Safety - Number of Patients Experiencing Any Grade 4 Adverse Event | Severity was assessed according to the toxicity criteria defined in the National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE), Version 3.0, where grade 1 denoted mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. In the case of adverse events not contained within the NCI-CTCAE, the investigator was responsible for assessing the severity of the AE (grades 1 to 4) based on the jeopardy to the subject's health and well-being, and the ability of the subject to function during the event. | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks |
| Safety - Number of Patients Experiencing Any Grade 3 or 4 Skin Reaction | Skin reactions were considered as adverse events of special interest and were evaluated in a special AE category composed of specific MedDRA preferred terms. Severity was assessed according to criteria defined in the NCI-CTCAE, Version 3.0, where grade 1 is mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks |
| Safety - Number of Patients Experiencing Any Grade 3 or 4 Infusion Related Reaction | Infusion related reactions were considered as adverse events of special interest and were evaluated in a special AE category composed of specific MedDRA preferred terms. Severity was assessed according to criteria defined in the NCI-CTCAE, Version 3.0, where grade 1 is mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks |
| Chiba |
| Japan |
| Research Site | Shizuoka | Japan |
| Research Site | Tokyo | Japan |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cetuximab With Radiotherapy | Subjects received cetuximab at an initial dose of 400 mg/m² infused 6 or 7 days before starting radiotherapy (RT). This was followed by subsequent weekly infusions of 250 mg/m² cetuximab administered in combination with radiotherapy (5 days/week) for 6 weeks. Subjects will receive cetuximab until radiographically documented progressive disease or unacceptable toxicity occurs or consent is withdrawn. If RT is delayed, administration of cetuximab every 7 days is continued. If RT is discontinued for any reason, treatment with cetuximab monotherapy every 7 days is continued. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | 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 | Completion Rate | Number of subjects who complete ≥70% of Cetuximab planned dose administration in terms of relative dose intensity of Cetuximab and full dose of RT ≤2 weeks over planned schedule in terms of RT duration ≤8 weeks, divided by the the number of subjects in the ITT/Safety population | ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment | Posted | Number | 95% Confidence Interval | percentage of participants | time from first administration of cetuximab to last administration of cetuximab or RT (whichever is later), ≤ 9 weeks |
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| |||||||||||||||||||||||||
| Secondary | Best Response Rate | Number of subjects experiencing a Complete Response (complete disappearance of measurable and evaluable disease without new lesions) or Partial Response (>=50% decrease of the sum of the product diameters of measurable disease, evaluable disease not worsening or progressing, no new lesions) at 8 weeks post radiotherapy (confirmed by repeat assessment at week 12) based on imaging according to modified World Health Organisation criteria as assessed independently by the Efficacy and Safety Evaluation Committee, divided by the number of subjects in the ITT/safety population | ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment | Posted | Number | 95% Confidence Interval | percentage of participants | best response was determined at week 8 post radiotherapy, for subjects with complete or partial response a confirmation in week 12 post radiotherapy was required |
| |||||||||||||||||||||||||||
| Secondary | Safety - Number of Patients Experiencing Any Adverse Event | Please refer to Adverse Events section for further details | ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment | Posted | Number | participants | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks |
|
| |||||||||||||||||||||||||||
| Secondary | Safety - Number of Patients Experiencing Any Grade 4 Adverse Event | Severity was assessed according to the toxicity criteria defined in the National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE), Version 3.0, where grade 1 denoted mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. In the case of adverse events not contained within the NCI-CTCAE, the investigator was responsible for assessing the severity of the AE (grades 1 to 4) based on the jeopardy to the subject's health and well-being, and the ability of the subject to function during the event. | ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment | Posted | Number | participants | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks |
| ||||||||||||||||||||||||||||
| Secondary | Safety - Number of Patients Experiencing Any Grade 3 or 4 Skin Reaction | Skin reactions were considered as adverse events of special interest and were evaluated in a special AE category composed of specific MedDRA preferred terms. Severity was assessed according to criteria defined in the NCI-CTCAE, Version 3.0, where grade 1 is mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. | ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment | Posted | Number | participants | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks |
|
| |||||||||||||||||||||||||||
| Secondary | Safety - Number of Patients Experiencing Any Grade 3 or 4 Infusion Related Reaction | Infusion related reactions were considered as adverse events of special interest and were evaluated in a special AE category composed of specific MedDRA preferred terms. Severity was assessed according to criteria defined in the NCI-CTCAE, Version 3.0, where grade 1 is mild, grade 2 moderate, grade 3 severe, and grade 4 lifethreatening or disabling. | ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment | Posted | Number | participants | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks |
|
|
Time from first dose up to 60 days after the last dose of study treatment. Adverse Events (AEs) are summarized using the MedDRA version 13.0.
Treatment emergent Adverse Events (TEAEs) were defined as AEs that emerge or worsen on or after the first dosing day of trial treatment until 60 days after the last trial treatment administration.
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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 With Radiotherapy | Subjects received cetuximab at an initial dose of 400 mg/m² infused 6 or 7 days before starting radiotherapy (RT). This was followed by subsequent weekly infusions of 250 mg/m² cetuximab administered in combination with radiotherapy (5 days/week) for 6 weeks. Subjects will receive cetuximab until radiographically documented progressive disease or unacceptable toxicity occurs or consent is withdrawn. If RT is delayed, administration of cetuximab every 7 days is continued. If RT is discontinued for any reason, treatment with cetuximab monotherapy every 7 days is continued. | 3 | 22 | 22 | 22 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 13.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 13.0 | Systematic Assessment |
| |
| Altered state of consciousness | Nervous system disorders | MedDRA version 13.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 13.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA version 13.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Cheilitis | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Odynophagia | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA version 13.0 | Systematic Assessment |
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| Mucosal inflammation | General disorders | MedDRA version 13.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA version 13.0 | Systematic Assessment |
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| Infection | Infections and infestations | MedDRA version 13.0 | Systematic Assessment |
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| Paronychia | Infections and infestations | MedDRA version 13.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA version 13.0 | Systematic Assessment |
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| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA version 13.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA version 13.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA version 13.0 | Systematic Assessment |
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| Blood albumin decreased | Investigations | MedDRA version 13.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA version 13.0 | Systematic Assessment |
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| Blood urea increased | Investigations | MedDRA version 13.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA version 13.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA version 13.0 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA version 13.0 | Systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 13.0 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA version 13.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 13.0 | Systematic Assessment |
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| Delirium | Psychiatric disorders | MedDRA version 13.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA version 13.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Pharyngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Pharyngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA version 13.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA version 13.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Masataka Ota | Merck Serono Co., Ltd, Tokyo, Japan | +81 0 3 6853 8611 |
| 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 |
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