E1305 A Phase III Randomized Trial of Chemotherapy With or WithoutBevacizumab in Patients with Recurrent or Metastatic Head and Neck Cancer
To compare the overall survival of patients with recurrent or metastatic head and neck cancer treated with standard cisplatin-based chemotherapy with or without Bevacizumab. Secondary objectives include assessing the toxicities associated with adding Bevacizumab to cisplatin doublets,and to compare the overall response and progressive free survival rates with these therapies. Blood and tumor tissue samples will be obtained at specific time points for future correlative studies.
Must have: histologically or cytologically confirmed Squamous Cell Cancer of the Head and Neck which is either a)recurrent- judged incurable by surgery or radiation or b)metastatic; No nasopharyngeal ca of histologic types WHO 2 or 3 or squamous cell carcinoma that originated in the skin; NO prior chemo,biologic/molecular targeted therapy for recurrent or metastatic SCCHN; may have received one regimen of induction, concomitant chemo/RT and/or adjuvant chemotherapy as part of initial potential curative therapy but MUST NOT HAVE RECEIVED PRIOR CHEMO FOR RECURRENT OR METASTATIC DISEASE. Minimum of 6 months is required between last dose of chemotherapy or chemoRT and study treatment;must be progession free for at least 6 months after completion of chemo or chemoRT or RT plus Cetuximab given with a curative intent(Cetuximab therapy: 6 months is required between last dose of chemo or chemoRT and study treatment if part of concurrent regimen,8 weeks if part of adjuvant regimen post radiation.Pts with progression after 2 cycles of induction chemotherapy are not eligible for the study. No prior treatment with Bevacizumb. Previous palliative RT of head/neck permitted as long as 8 weeks have elapsed between end of RT and entry into protocol; NO prior re-irradiation to head/neck permitted; minimum of 3 weeks must elapse between prior radiation to other areas of the body and study entry; ECOG PS equal to 0-1; must not be receiving any other investigational agent while on study; must have fully recovered from effects of previous surgery, chemotherapy or RT-should be greater than 4 weeks post surgery; must have measurable disease per RECIST( see sec. 6 of protocol) baseline measurements and evaluations of all sites of disease must be obtained less than / equal to 4 weeks prior to randomization;disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual cancer following RT; persistent disease after RT must be biopsy-proven at least 8 weeks after completion of RT; adequate bone marrow, kidney and liver functions less than / equal to 2 weeks prior to randomization; urine protein creatinine ratio should be screened less than / equal to 2 weeks prior to randomization; no known brain mets; no history of coagulopathy or hemorrhagic disorders- May not have:tumors that invade major vessels(carotid), central lung mets that are cavitary(within 2 cm from the hilum),any prior history of bleeding related to the current head/neck cancer,history of gross hemoptysis(bright red blood of 1/2 tsp or more per coughing episode) less than / equal to 3 months prior to enrollment.No h/o thrombosis currently requiring anticoagulation-INR less than 1.5 at registration;No chronic daily treatment with NSAIDS or aspirin greater than 325 mg/d which is known to inhibit platelet function; no hypercalcemia related to head/neck cancer; h/o squamous cell or basal cell ca of skin or in situ ca of the cervix must have been curatively treated; h/o other malignancy must have been treated with curative intent and remained disease free for 5 yrs post diagnosis; no current peripheral neuropathy greater than / equal to gr 2 at time of randomization; no other illness/condition that would preclude full compliance with the study; no prior h/o allergic reaction to Docetaxel or other drugs formulated with polysorbate 80; BP less than / equal to to 150/90 less than / equal to 2 weeks prior to randomization;pts with h/o hypertension must be well controlled prior to study entry( less than / equal to 150/90) on a stable anti-hypertensive regimen;no major surgical procedure, biopsy, or significant traumatic injury within 28 days prior to enrollment(or anticipated need for major surgical procedure during study enrollment)NO H/O abdominal fistula,GI perforation, or intra-abdominal abcess within 28 days prior to registration; no serious non-healing wounds, ulcers or bone fractures;no unstable angina,or MI within the previous 6 months; no symptomatic CHF-NYHA GrII or greater; no prior h/o of a serious human antibody reaction; greater than / equal to 18 yrs of age; no pregnant or breast feeding females; both males and females must agree to use an adequate hormonal or barrier form of contraception prior to study entry and for the duration of study participation; women must have a urine pregnancy test performed within 2 weeks prior to study entry to r/o pregnancy; HIV + pts receiving combination anti-retriovirals are excluded.
Treatment ARM A: 1A- Docetaxel and Cisplatin repeated every 21 days: Docetaxel 75mg/m2IV over 1 hr day 1 followed by Cisplatin 75mg/m2 IV over 1-2 hrs day 1 2A- Cisplatin and 5FU repeated every 21 days: Cisplatin 100 mg/m2 IV over 1-2 hrs on day 1 followed by 5-FU 1000 mg/m2/day as a continuous infusion x 4 days Treatment ARM B: 1B-Bevacizumab added to the above Arm1A repeated every 21 days 2B-Bevacizumab added to the above Arm2A repeated every 21 days
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