Carcinoma of the Head and Neck
Conditions
Keywords
Newly diagnosed locally advanced squamous cell carcinoma of the head and neck (SCCHN)
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.
Interventions
DRUGCetuximab
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receive Cetuximab until radiographically documented progressive disease or unacceptable toxicity occurs or consent is withdrawn.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.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient has pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx, or larynx. 2. The patient has been confirmed Epidermal Growth Factor Receptor expressing in tumor specimen by immunohistochemistry. 3. 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. 4. The patient has at least bi-dimensionally measurable disease. 5. The patient is medically suitable to withstand a course of the definitive radiation therapy. 6. The patient aged ≥ 20 years old at informed consent 7. The patient's Karnofsky performance status is ≥ 60 8. Hemoglobin ≥ 9g/dL 9. Neutrophil ≥ 1500/mm\^3 10. Platelet ≥ 100,000/mm\^3 11. Total Bilirubin ≤ 1.5 mg/dL 12. Aspartate Aminotransferase ≤ 2 x the upper limit of normal 13. Alanine Aminotransferase ≤ 2 x the upper limit of normal 14. Serum creatinine ≤ 1.5 mg/dL 15. Serum calcium concentration: within normality 16. The patient is eligible if disease free from a previously treated malignancy for greater than three years. 17. The patient agrees to use effective contraception if procreative potential exists. 18. The patient has given signed informed consent 19. The patient who is a Japanese with Japanese citizenship
Exclusion criteria
1. 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. 2. The patient has squamous cell carcinoma arising in the nasopharynx or oral cavity. 3. The patient has received prior systemic chemotherapy within the last three years. 4. The patient has undergone previous surgery for the tumor under study other than biopsy. 5. The patient has received prior radiation therapy to the head and neck. 6. The patient's radiation therapy is considered to be a part of a postoperative regimen following primary surgical resection. 7. The patient is pregnant or breast feeding. 8. 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. 9. 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). 10. The patient has uncontrolled diabetes mellitus, malignant hypertension, or liver failure. 11. The patient has or has suffered from a pulmonary fibrosis, acute pulmonary disorder, or interstitial pneumonia. 12. 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. 13. 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 14. The patient has a dental disease which requires incision and drainage. 15. 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. 16. The patient has been received some investigational medication within 30 days before study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completion Rate | time from first administration of cetuximab to last administration of cetuximab or RT (whichever is later), ≤ 9 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Best Response Rate | 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 | 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 | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks | Please refer to Adverse Events section for further details |
| Safety - Number of Patients Experiencing Any Grade 4 Adverse Event | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks | 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 | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks | 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 | time from first dose up to 60 days after last dose of study treatment, ≤18 weeks | 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. |
Countries
Japan
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive disease | 1 |
Baseline characteristics
| Characteristic | Cetuximab With Radiotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 67.6 years STANDARD_DEVIATION 6.59 |
| Region of Enrollment Japan | 22 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 3 / 22 |
Outcome results
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
Time frame: time from first administration of cetuximab to last administration of cetuximab or RT (whichever is later), ≤ 9 weeks
Population: ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab With Radiotherapy | Completion Rate | 100 percentage of participants |
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
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
Population: ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab With Radiotherapy | Best Response Rate | 81.8 percentage of participants |
Secondary
Safety - Number of Patients Experiencing Any Adverse Event
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
Population: ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab With Radiotherapy | Safety - Number of Patients Experiencing Any Adverse Event | 22 participants |
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.
Time frame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
Population: ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab With Radiotherapy | Safety - Number of Patients Experiencing Any Grade 3 or 4 Infusion Related Reaction | 0 participants |
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.
Time frame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
Population: ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab With Radiotherapy | Safety - Number of Patients Experiencing Any Grade 3 or 4 Skin Reaction | 3 participants |
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.
Time frame: time from first dose up to 60 days after last dose of study treatment, ≤18 weeks
Population: ITT/Safety population, i.e. all subjects who have received at least one dose of the study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab With Radiotherapy | Safety - Number of Patients Experiencing Any Grade 4 Adverse Event | 2 participants |