Overview

This trial is active, not recruiting.

Condition head and neck cancer
Treatments cetuximab, cisplatin
Phase phase 3
Target EGFR
Sponsor Radiation Therapy Oncology Group
Collaborator National Cancer Institute (NCI)
Start date November 2005
End date June 2016
Trial size 720 participants
Trial identifier NCT00265941, CDR0000458049, NCI-2009-00729, RTOG 0522

Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Patients receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.
cisplatin
Given IV
(Experimental)
Patients receive cetuximab IV over 1-2 hours once in weeks 0-7 and cisplatin as in arm I.
cetuximab
Given IV
cisplatin
Given IV

Primary Outcomes

Measure
Disease-free survival (DFS)
time frame: From randomization to date of failure (local, regional or distant progression or death) or last follow-up. Analysis occurs after 434 failures have been reported.

Secondary Outcomes

Measure
Overall survival (OS)
time frame: From randomization to date of death or last follow-up. Analysis occurs after 434 failures have been reported.
Local-regional control (LRC)
time frame: From randomization to date of failure (local or regional progression) or distant progression or death or last follow-up. Analysis occurs after 434 failures have been reported.
Mucositis toxicity ≥ grade 3
time frame: From start of treatment to last follow-up
Other toxicity ≥ grade 3
time frame: From start of treatment to last follow-up
Protocol treatment delivery
time frame: From start of treatment to end of treatment
Death ≤ 30 days after discontinuation of protocol treatment
time frame: From start of treatment to 30 days after the end of treatment
Quality of life as measured by Performance Status Scale for Head and Neck Cancer and the European Quality of Life questionnaire (EQ-5D)
time frame: From randomization to 5 years
Quality of life as measured by Functional Assessment of Cancer Therapy-General version
time frame: From randomization to 5 years
Correlation of expression of epidermal growth factor receptor or its down-stream molecules (e.g., MAPK, AKT, Stat-3, PKC) with DFS, OS, and LRC
time frame: From randomization to date of death or last follow-up
Correlation of pre-treatment positron emission tomography (PET)/CT scan findings with DFS, OS, and LRC
time frame: From randomization to date of death or last follow-up
Correlation of post-treatment PET/CT scan findings with pathologic nodal complete response and nodal relapse rate at 2 years in clinical N2-3 patients
time frame: From randomization to 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically proven (from primary lesion and/or lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx - Stage III or IV disease (T2, N2-3, M0; T3-4, any N, M0) - No distant metastases - The following primary tumor sites are excluded: - Oral cavity - Nasopharynx - Sinuses - Salivary glands PATIENT CHARACTERISTICS: - Zubrod performance status 0-1 - Absolute neutrophil count (ANC) ≥ 1,800/mm^3 - Platelets ≥ 100,000/mm^3 - Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable) - Bilirubin ≤ 1.5 mg/dL (Gilbert's disease as the sole cause of elevated bilirubin may be allowed at the discretion of the principal investigator) - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2 times the upper limit of normal - Serum creatinine ≤ 1.5 mg/dL - Creatinine clearance ≥ 50 mL/min - Not pregnant or nursing - Negative pregnancy test - Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment) - No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years - No unstable angina and/or congestive heart failure requiring hospitalization in past 6 months - Left ventricular ejection fraction ≥ 45% - No transmural myocardial infarction within the last 6 months - No acute bacterial or fungal infection requiring intravenous antibiotics - No chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy - No acquired immune deficiency syndrome (AIDS) - HIV testing is not required for entry into this protocol - Protocol-specific requirements may also exclude immuno-compromised patients - No prior allergic reaction to the study drug(s) - No other uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures - No comorbidity of uncontrolled diabetes (i.e., symptomatic hyperglycemia) - No other severe active comorbidity PRIOR CONCURRENT THERAPY: - No prior systemic chemotherapy for the study cancer - Prior chemotherapy for a different cancer is allowed - No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields - No initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease) - No radical or modified neck dissection - No prior therapy that specifically and directly targets the EGFR pathway

Additional Information

Official title A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas
Principal investigator David Rosenthal, MD
Description OBJECTIVES: Primary - Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve disease-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. Secondary - Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients. - Correlate the expression of epidermal growth factor receptor (EGFR) and its down-stream molecules with outcome in patients participating in this component of the trial. - Correlate pre-treatment PET scan findings with disease-free survival, overall survival, and local-regional control in patients participating in this component of the trial. - Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial. OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients undergo either 3D-conformal radiotherapy or IMRT once or twice a day, 5 or 6 days a week, for 6 weeks. Patients also receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy. - Arm II: Patients receive cetuximab IV over 1-2 hours once in weeks 0-7. Beginning in week 1, patients also undergo radiotherapy and receive cisplatin as in arm I. In both arms, patients with persistent nodal disease (any stage) (i.e., a residual palpable or radiographic abnormality) undergo neck dissection* approximately 9-10 weeks after completion of treatment. NOTE: *A neck dissection is optional for patients with multiple lymph nodes or lymph nodes > 3 cm in diameter who achieve a complete clinical and radiographic response in the neck. Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years. After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter. PROJECTED ACCRUAL: Approximately 720 patients will be accrued for this study.
Trial information was received from ClinicalTrials.gov and was last updated in November 2015.
Information provided to ClinicalTrials.gov by Radiation Therapy Oncology Group.