Overview

This trial is active, not recruiting.

Condition head and neck cancer
Treatments cetuximab, cisplatin, docetaxel, radiation therapy
Phase phase 2
Target EGFR
Sponsor Radiation Therapy Oncology Group
Collaborator National Cancer Institute (NCI)
Start date April 2004
End date March 2009
Trial size 238 participants
Trial identifier NCT00084318, CDR0000360850, NCT00414674, RTOG-0234

Summary

RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Cisplatin and docetaxel may make the tumor cells more sensitive to radiation therapy. Combining a monoclonal antibody with chemoradiotherapy and giving them after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying adjuvant cetuximab given together with chemoradiotherapy using cisplatin to see how well it works compared to adjuvant cetuximab given together with chemoradiotherapy using docetaxel in treating patients with resected stage III or stage IV squamous cell carcinoma (cancer) or lymphoepithelioma of the head and neck.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.
cetuximab
400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.
cisplatin
30 mg/m^2 intravenously infused over over 60 minutes in weeks 2 through 7.
radiation therapy
60 Gy (2 Gy once a day, 5 times a week)
(Experimental)
Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
cetuximab
400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.
docetaxel
15 mg/m^2 intravenously infused over 30 minutes in weeks 2 through 7.
radiation therapy
60 Gy (2 Gy once a day, 5 times a week)

Primary Outcomes

Measure
Disease-free Survival
time frame: From randomization to 2 years

Secondary Outcomes

Measure
Overall Survival
time frame: From randomization to 2 years
Treatment Tolerance
time frame: From start of treatment to end of treatment (protocol treatment lasts seven weeks).
Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4)
time frame: From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis.
Frequency of Other Acute and Late Toxicity
time frame: From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis.
Local-regional Control
time frame: From randomization to 2 years
Correlation of EGFR (Total and Phosphorylated) pMAPK, pAKT, Stat-3, KI-67, COX-2, and Cyclin B1 Expression With Local-regional Control, and Overall and Disease-free Survival
time frame: From randomization to two years

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed squamous cell carcinoma of the head and neck meeting the following criteria: - Site of tumor origin in the oral cavity, oropharynx, larynx, or hypopharynx (excluding lip, nasopharynx, or sinuses) - Gross total resection must be completed within 7 weeks of randomization, with pathology demonstrating one or more of the following risk factors: - Histologic extracapsular nodal extension - Histologic involvement of ≥ 2 regional lymph nodes - Invasive cancer seen on microscopic evaluation of the resection margin, with no evidence of gross tumor residual. - Tonsillar cancer patients who undergo transoral excision of all gross tumor are eligible provided extracapsular nodal extension or involvement of ≥ 2 regional lymph nodes is histologically confirmed - American Joint Committee on Cancer (AJCC) pathological stage III or IV - No evidence of distant metastases - No synchronous or concurrent head and neck primary tumors PATIENT CHARACTERISTICS: Age - 18 and over Performance status - Zubrod 0-1 Life expectancy - Not specified Hematopoietic - Absolute neutrophil count ≥ 2,000/mm^3 - Platelet count ≥ 100,000/mm^3 - Hemoglobin > 8.0 g/dL Hepatic - Bilirubin ≤ 1.5 times upper limit of normal (ULN) - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT), and alkaline phosphatase meeting 1 of the following parameters: - Alkaline phosphatase ≤ ULN AND AST or ALT ≤ 5 times ULN - Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN - Alkaline phosphatase ≤ 5 times ULN AND AST or ALT ≤ ULN Renal - Creatinine ≤ 1.5 mg/dL Cardiovascular - No unstable angina - No uncontrolled hypertension - No myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass surgery or percutaneous transluminal coronary angioplasty) - No uncontrolled arrhythmia - No congestive heart failure - No more than 2 heart-related hospitalizations within the past year - No other active cardiac disease Pulmonary - No more than 2 hospitalizations for chronic obstructive pulmonary disease within the past year Neurologic - No pre-existing peripheral neuropathy ≥ grade 2 - No uncontrolled seizure disorder - No active neurological disease Other - No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 - No other invasive malignancy within the past 3 years except nonmelanoma skin cancer - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy - No prior anti-epidermal growth factor receptor antibody therapy Chemotherapy - More than 3 years since prior cytotoxic chemotherapy Endocrine therapy - Not specified Radiotherapy - No prior head and neck radiotherapy Surgery - See Disease Characteristics Other - No prior tyrosine kinase inhibitor therapy

Additional Information

Official title A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck
Principal investigator Paul M. Harari, MD
Description OBJECTIVES: Primary - Compare disease-free survival of patients with resected stage III or IV squamous cell carcinoma or lymphoepithelioma of the head and neck treated with adjuvant cetuximab in combination with chemoradiotherapy comprising docetaxel vs cisplatin. Secondary - Compare the safety and efficacy of these regimens in these patients. - Compare locoregional control and overall survival rates in patients treated with these regimens. - Correlate epidermal growth factor receptor (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, cyclo-oxygenase-2, and cyclin B1 expression with outcome in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1), risk category (positive margins vs high risk [i.e., ≥ 2 positive nodes or extracapsular nodal extension]) and use of intensity-modulated radiotherapy (no vs yes). Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive cetuximab IV over 2 hours on day 1 (week 1). Patients then receive cetuximab IV over 1 hour and cisplatin IV over 1 hour before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Patients undergo radiotherapy once daily, 5 days a week, beginning on day 8 for a total of 6 weeks (weeks 2-7). - Arm II: Patients receive cetuximab and undergo radiotherapy as in arm I. Patients also receive docetaxel IV over 30 minutes before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 4 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within approximately 29 months.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Radiation Therapy Oncology Group.