Back to resultsStudy of Cetuximab With Concomitant-boost Radiotherapy in Patients With Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Primary Purpose
Carcinoma of the Head and Neck
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma of the Head and Neck focused on measuring Newly diagnosed locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Eligibility Criteria
Inclusion Criteria:
- The patient has pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx, or larynx.
- The patient has been confirmed Epidermal Growth Factor Receptor expressing in tumor specimen by immunohistochemistry.
- The patient has stage III or IV disease (Unio Internationalis Contra Cancrum / International Union against Cancer Tumor-Lymph Nodes-Metastases classification) with an expected survival of ≥ 12 months.
- The patient has at least bi-dimensionally measurable disease.
- The patient is medically suitable to withstand a course of the definitive radiation therapy.
- The patient aged ≥ 20 years old at informed consent
- The patient's Karnofsky performance status is ≥ 60
- Hemoglobin ≥ 9g/dL
- Neutrophil ≥ 1500/mm^3
- Platelet ≥ 100,000/mm^3
- Total Bilirubin ≤ 1.5 mg/dL
- Aspartate Aminotransferase ≤ 2 x the upper limit of normal
- Alanine Aminotransferase ≤ 2 x the upper limit of normal
- Serum creatinine ≤ 1.5 mg/dL
- Serum calcium concentration: within normality
- The patient is eligible if disease free from a previously treated malignancy for greater than three years.
- The patient agrees to use effective contraception if procreative potential exists.
- The patient has given signed informed consent
- The patient who is a Japanese with Japanese citizenship
Exclusion Criteria:
- The patient has evidence of distant metastatic disease. The patient who has any metastatic disease documented by Magnetic Resonance Imaging for the head and neck, and Computed Tomography for the chest and abdomen should be excluded.
- The patient has squamous cell carcinoma arising in the nasopharynx or oral cavity.
- The patient has received prior systemic chemotherapy within the last three years.
- The patient has undergone previous surgery for the tumor under study other than biopsy.
- The patient has received prior radiation therapy to the head and neck.
- The patient's radiation therapy is considered to be a part of a postoperative regimen following primary surgical resection.
- The patient is pregnant or breast feeding.
- The patient has received prior Cetuximab or murine monoclonal antibody (including chimeric antibody) therapy or a history of severe hypersensitivity to any component of Cetuximab solution for Injection.
- The patient has a medical or psychological condition that would not permit the patient to complete the study or sign informed consent (including drug abuse).
- The patient has uncontrolled diabetes mellitus, malignant hypertension, or liver failure.
- The patient has or has suffered from a pulmonary fibrosis, acute pulmonary disorder, or interstitial pneumonia.
- The patient has an active infection (infection requiring intravenous anti-bacterial, anti-fungus, or anti-viral agent), or known and declared Human Immunodeficiency Virus infection.
- The patient has a clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency
- The patient has a dental disease which requires incision and drainage.
- The patient has active multiple cancers (excluding skin cancer except for melanoma, and carcinoma in situ of the cervix or the digestive tract) in the last 3 years.
- The patient has been received some investigational medication within 30 days before study entry.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cetuximab With Radiotherapy
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Safety - Number of Patients Experiencing Any Adverse Event
Please refer to Adverse Events section for further details
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.
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.
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.
Full Information
NCT ID
NCT00865098
First Posted
March 18, 2009
Last Updated
February 10, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT00865098
Brief Title
Study of Cetuximab With Concomitant-boost Radiotherapy in Patients With Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Official Title
Open-label, Non-randomized, Non-controlled, Multicenter Phase II Study Investigating Cetuximab in Combination With Concomitant-boost Radiotherapy as First-line Treatment for Japanese Patients With Newly Diagnosed Locally Advanced SCCHN.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma of the Head and Neck
Keywords
Newly diagnosed locally advanced squamous cell carcinoma of the head and neck (SCCHN)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cetuximab With Radiotherapy
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Completion Rate
Description
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 Frame
time from first administration of cetuximab to last administration of cetuximab or RT (whichever is later), ≤ 9 weeks
Secondary Outcome Measure Information:
Title
Best Response Rate
Description
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
Time Frame
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
Title
Safety - Number of Patients Experiencing Any Adverse Event
Description
Please refer to Adverse Events section for further details
Time Frame
time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
Title
Safety - Number of Patients Experiencing Any Grade 4 Adverse Event
Description
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 Frame
time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
Title
Safety - Number of Patients Experiencing Any Grade 3 or 4 Skin Reaction
Description
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 Frame
time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
Title
Safety - Number of Patients Experiencing Any Grade 3 or 4 Infusion Related Reaction
Description
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 Frame
time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient has pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx, or larynx.
The patient has been confirmed Epidermal Growth Factor Receptor expressing in tumor specimen by immunohistochemistry.
The patient has stage III or IV disease (Unio Internationalis Contra Cancrum / International Union against Cancer Tumor-Lymph Nodes-Metastases classification) with an expected survival of ≥ 12 months.
The patient has at least bi-dimensionally measurable disease.
The patient is medically suitable to withstand a course of the definitive radiation therapy.
The patient aged ≥ 20 years old at informed consent
The patient's Karnofsky performance status is ≥ 60
Hemoglobin ≥ 9g/dL
Neutrophil ≥ 1500/mm^3
Platelet ≥ 100,000/mm^3
Total Bilirubin ≤ 1.5 mg/dL
Aspartate Aminotransferase ≤ 2 x the upper limit of normal
Alanine Aminotransferase ≤ 2 x the upper limit of normal
Serum creatinine ≤ 1.5 mg/dL
Serum calcium concentration: within normality
The patient is eligible if disease free from a previously treated malignancy for greater than three years.
The patient agrees to use effective contraception if procreative potential exists.
The patient has given signed informed consent
The patient who is a Japanese with Japanese citizenship
Exclusion Criteria:
The patient has evidence of distant metastatic disease. The patient who has any metastatic disease documented by Magnetic Resonance Imaging for the head and neck, and Computed Tomography for the chest and abdomen should be excluded.
The patient has squamous cell carcinoma arising in the nasopharynx or oral cavity.
The patient has received prior systemic chemotherapy within the last three years.
The patient has undergone previous surgery for the tumor under study other than biopsy.
The patient has received prior radiation therapy to the head and neck.
The patient's radiation therapy is considered to be a part of a postoperative regimen following primary surgical resection.
The patient is pregnant or breast feeding.
The patient has received prior Cetuximab or murine monoclonal antibody (including chimeric antibody) therapy or a history of severe hypersensitivity to any component of Cetuximab solution for Injection.
The patient has a medical or psychological condition that would not permit the patient to complete the study or sign informed consent (including drug abuse).
The patient has uncontrolled diabetes mellitus, malignant hypertension, or liver failure.
The patient has or has suffered from a pulmonary fibrosis, acute pulmonary disorder, or interstitial pneumonia.
The patient has an active infection (infection requiring intravenous anti-bacterial, anti-fungus, or anti-viral agent), or known and declared Human Immunodeficiency Virus infection.
The patient has a clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency
The patient has a dental disease which requires incision and drainage.
The patient has active multiple cancers (excluding skin cancer except for melanoma, and carcinoma in situ of the cervix or the digestive tract) in the last 3 years.
The patient has been received some investigational medication within 30 days before study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Masataka Ota, MD
Organizational Affiliation
Merck Serono Co.,Ltd, an Affilate of Merck Serono, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Aichi
Country
Japan
Facility Name
Research Site
City
Chiba
Country
Japan
Facility Name
Research Site
City
Shizuoka
Country
Japan
Facility Name
Research Site
City
Tokyo
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
23479383
Citation
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.
Results Reference
result
Learn more about this trial
Study of Cetuximab With Concomitant-boost Radiotherapy in Patients With Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
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