Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous... | NCT00084318 | Trialant

Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous... | NCT00084318 | Trialant

Official Title: A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck
Brief 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.
Detailed 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.

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Eligibility Criteria: 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