Phase III Randomized, Placebo Controlled, Trial Of Docetaxel Versus Docetaxel Plus ZD1839 (Iressa, Gefitinib, NSC 715055) In Performance Status 2 Or Previously Treated Patients With Recurrent Or Metastatic Head And Neck Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck; patient must not have nasopharyngeal carcinoma of histologic types WHO 2 and 3
• Metastatic or locally recurrent carcinoma of the head and neck that is considered incurable by local therapies
• Any number of prior chemotherapy or biologic/targeted therapy regimens is allowed
• No prior therapy with docetaxel at any time (even if part of prior curative treatment

• No prior systemic EGFR inhibitors, such as ZD1839 (Iressa, gefitinib)/Iressa (AstraZeneca), ABX-EBX (Abgenix), MDX-447 (Medarex/Merck), OSI-774/Tarceva (OSI pharmaceuticals), C225/Cetuximab (ImClone), PKI166 (Novartis), CI-1033 (Parke-Davis), EKB-569 (Wyeth Ayerst); treatment with paclitaxel is allowed if the patient did not progress while on paclitaxel

  • NOTE: the use of cetuximab given concurrently with radiation or chemoradiotherapy for up to 9 total weekly doses, as part of initial potentially curative therapy is allowed, if completed > 6 months prior to registration
• Patients must not be receiving any other investigational agent while on the study

• Patients must have either:

  • Strata A:

    • ECOG performance status 2 (in bed 50% of the time. Ambulatory and capable of all self-care, but unable to carry out any work activities; up and about more than 50% of waking hours), AND no prior chemotherapy for recurrent metastatic head and neck cancer OR

  • Strata B

    • PS 0-2 AND prior chemotherapy (i.e. one or more prior chemotherapy regimens (without docetaxel)) for locally recurrent/metastatic disease or exposure to prior chemotherapy (without docetaxel) as part of primary curative therapy < 6 months prior to randomization; patients who receive chemotherapy as part of potentially curative therapy of primary disease within 6 months of randomization will be considered as having prior chemotherapy for recurrent/metastatic disease, whereas patients who received chemotherapy as part of potentially curative therapy of disease > 6 months of randomization will be considered as having no prior chemotherapy for recurrent/metastatic disease

• Patients must have fully recovered from the effects of any prior surgery, chemotherapy, or radiation therapy

  • A minimum time period of 3 weeks must elapse between the completion of radiation therapy and randomization to the study
  • A minimum period of 4 weeks must elapse between the last administration of any prior chemotherapy and randomization to the study
  • At least 2 weeks must elapse between the last administration of biologic/targeted therapy and randomization to the study
  • Patients must be > 3 weeks since major surgery, or significant traumatic injury prior to randomization
• No unstable systemic disease, including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or serious arrhythmia requiring medication
• Absolute neutrophil count (ANC) >= 1500 /mm^3
• Platelets >= 100,000 /mm^3
• Hemoglobin >= 8.0 g/dl
• Bilirubin within normal limits
• Alkaline phosphatase, SGOT (AST), and SGPT
• Creatinine < 2.0 or creatinine clearance of > 60 ml/min
• No hypercalcemia related to head and neck cancer
• No known brain metastasis
• Females should not be pregnant or breast feeding because chemotherapy may be harmful to the fetus or the nursing infant; also, the effects of ZD1839 (Iressa, gefitinib) on the developing human fetus are unknown
• All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy
• Women of childbearing potential and sexually active males must use an accepted and effective method of contraception while on treatment and for three months after the completion of treatment

• Patients must have measurable or non-measurable disease based on RECIST; baseline measurements and evaluations must be obtained < 4 weeks of randomization; all areas of disease should be recorded and mapped out in order to assess response and uniformity of response to therapy; disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy; persistent disease after radiotherapy must be biopsy proven at least 8 weeks after completion of radiation therapy

  • Radiographic findings are acceptable providing that clear-cut measurements can be made
• Patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 5 years post diagnosis
• No current peripheral neuropathy >= grade 2 at time of randomization
• Patients must not have any co-existing condition that would preclude full compliance with the study
• No known hypersensitivity to ZD1839 (Iressa, gefitinib) or any excipients of this product; no prior history of severe hypersensitivity reaction to Docetaxel or other drugs formulated with polysorbate 80
• Drugs that are CYP3A4 inhibitors should be generally avoided and if possible, discontinued, 1 week prior to initiating study drug; however, if medically necessary, they can be taken with caution after consulting with the study chair

• From patients consenting to participate in the correlative studies:

  • Tissues must be submitted as outlined in Section 10; if tissue cannot be submitted, written justification must be submitted to the ECOG Pathology Coordinating Office
• HIV positive patient's receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with ZD1839 (Iressa, gefitinib)
• Patients may not have had tumor-related hemorrhagic events in the previous three months that required as major medical intervention, such as surgery or embolization
• Patients must not be on therapeutic anticoagulation or have tumors that are unequivocally invading major vessels (e.g. carotid artery)