Phase III Trial Of Docetaxel Versus Docetaxel Plus ZD1839 In Head And Neck Cancer
Condition: Recurrent Head and Neck Cancer; Metastatic Head and Neck Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: docetaxel; placebo; gefitinib
Intervention description: Given IV; Given orally; Given orally
Intervention MeSH terms: Docetaxel; Gefitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 270.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: docetaxel; gefitinib; head and neck cancer

Summary:

      Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells
      from dividing so they stop growing or die. Gefitinib may stop the growth of tumor cells by
      blocking the enzymes necessary for their growth. Combining docetaxel with gefitinib may kill
      more tumor cells. It is not yet known whether docetaxel is more effective with or without
      gefitinib in treating head and neck cancer. This randomized phase III trial is studying
      docetaxel and gefitinib to see how well they work compared to docetaxel alone in treating
      patients with metastatic or locally recurrent head and neck cancer.
    

Eligibility criteria:

        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