Phase III Trial Of Docetaxel Versus Docetaxel Plus ZD1839 In 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 World Health
   Organization (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 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 receiving any other investigational agent while on the study

   - Patients must have either:

      - Strata A:

         - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 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

   - Absolute neutrophil count (ANC) >= 1500 /mm^3

   - Platelets >= 100,000 /mm^3

   - Hemoglobin >= 8.0 g/dl

   - Bilirubin within normal limits

   - Creatinine < 2.0 or creatinine clearance of > 60 ml/min

   - 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 Response Evaluation
   Criteria In Solid Tumors (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

   - Drugs that are Cytochrome P450 3A4 (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

Exclusion criteria:

   - Prior therapy with docetaxel at any time (even if part of prior curative treatment)

   - Unstable systemic disease, including active infection, uncontrolled hypertension,
   unstable angina, congestive heart failure, or serious arrhythmia requiring medication

   - Hypercalcemia related to head and neck cancer

   - Brain metastasis

   - Current peripheral neuropathy >= grade 2 at time of randomization

   - Patients have co-existing condition that would preclude full compliance with the study

   - Known hypersensitivity to ZD1839 (Iressa, gefitinib) or any excipients of this
   product; prior history of severe hypersensitivity reaction to Docetaxel or other drugs
   formulated with polysorbate 80

   - HIV positive patient's receiving combination anti-retroviral therapy are excluded from
   the study because of possible pharmacokinetic interactions with ZD1839 (Iressa,
   gefitinib)

   - Patients have had tumor-related hemorrhagic events in the previous three months that
   required as major medical intervention, such as surgery or embolization

   - Patients are on therapeutic anticoagulation or have tumors that are unequivocally
   invading major vessels (e.g. carotid artery)

   - Females are 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