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 use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of cetuximab plus cisplatin in treating patients who have metastatic or recurrent cancer of the head and neck that has not responded to previous cisplatin-based chemotherapy.

Condition	Treatment or Intervention	Phase
Nose Cancer Oral Cancer Throat Cancer	Drug: cetuximab  Drug: cisplatin  Drug: fluorouracil  Drug: paclitaxel	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the response rate, duration of response, and survival in patients with metastatic or recurrent squamous cell carcinoma of the head and neck treated with cetuximab and cisplatin after failure of an initial cisplatin-based chemotherapy regimen. II. Determine the efficacy, safety, and toxicity of this regimen in these patients. III. Assess the quality of life of patients treated with this regimen.

PROTOCOL OUTLINE: This is a multicenter study. Part I (courses 1 and 2): Patients are assigned to 1 of 2 treatment groups based on prior cisplatin-based chemotherapy regimen: Group 1 (prior cisplatin with paclitaxel): Patients receive cisplatin IV over 1 hour on day 1 and fluorouracil IV continuously on days 1-4. Group 2 (prior cisplatin with fluorouracil): Patients receive cisplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Both groups: Treatment repeats every 3 weeks for 2 courses. Patients who achieve partial or complete response after completion of course 2 are taken off study. Patients with stable disease or disease progression after completion of course 2 proceed to part II of the study. Part II (courses 3-6): Patients are stratified by response to initial cisplatin-based chemotherapy regimen (stable disease vs disease progression). Patients receive a test dose of cetuximab IV over 10 minutes on day 1. Patients who do not experience grade 4 anaphylactic reaction receive a loading dose of cetuximab IV over 2 hours beginning 30 minutes after completion of test dose. Patients receive cisplatin IV over 1 hour beginning 1 hour after completion of cetuximab infusion on day 1. Patients receive maintenance cetuximab IV over 1 hour on day 8. Maintenance cetuximab repeats weekly. Combination treatment repeats every 3 weeks for a maximum of 4 courses. Patients with stable or responding disease after completion of course 6 may continue to receive cetuximab alone in the absence of disease progression and at the discretion of the protocol investigator and sponsor. Quality of life is assessed before course 1, at the completion of courses 2, 4, and 6, and then at 4 weeks after completion of study. Patients are followed at 4 weeks.

PROJECTED ACCRUAL: Approximately 175 patients will be accrued for this study within 8 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven metastatic or recurrent squamous cell carcinoma of the head and neck; Failure to respond to initial treatment with cisplatin and paclitaxel or cisplatin and fluorouracil
• Bidimensionally measurable disease
• Sufficient tumor tissue available for immunohistochemical determination of epidermal growth factor receptor expression
• No meningeal or CNS involvement by tumor

--Prior/Concurrent Therapy--

• Biologic therapy: No prior murine monoclonal antibody therapy or cetuximab
• Chemotherapy: See Disease Characteristics; More than 1 year since prior chemotherapy and recovered; Cumulative total dose of prior platinum therapy no greater than 200 mg/m2; No other concurrent chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: At least 2 months since prior radiotherapy (1 month if disease progression occurred during radiotherapy); No concurrent radiotherapy
• Surgery: At least 2 months since prior surgery except diagnostic biopsy
• Other: At least 1 month since prior investigational agent

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3; WBC at least 3,000/mm3; Hemoglobin at least 9 g/dL
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN); Alkaline phosphatase no greater than 2.5 times ULN; AST and ALT no greater than 2.5 times ULN
• Renal: Creatinine no greater than 1.5 mg/dL; Creatinine clearance at least 60 mL/min
• Cardiovascular: No history of clinically significant cardiac disease, serious arrhythmias, or significant conduction abnormalities
• Neurologic: No uncontrolled seizure disorder; No active neurologic disease; No neuropathy greater than grade 1
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; No other malignancy within the past 3 years except basal cell skin cancer or preinvasive carcinoma of the cervix

New Jersey
      Cooper Cancer Institute, Camden,  New Jersey,  08103,  United States
      ImClone Systems, Incorporated, Somerville,  New Jersey,  08876,  United States
      Kimball Medical Center, Lakewood,  New Jersey,  08701,  United States
      Monmouth Medical Center, Long Branch,  New Jersey,  07740,  United States

Study chairs or principal investigators

Fairooz F. Kabbinavar,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067521; UCLA-9906095; NCI-G00-1667; IMCL-CP02-9816; UAB-9917
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004865
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08