A Phase III Randomized Trial of Chemotherapy with or without Bevacizumab in Patients with Recurrent or Metastatic Head and Neck Cancer (ECOG E1305)
Trial Purpose and Description
Three regimens on this trial stratified by ECOG PS, Weight Loss, Prior Radtn to HN, Chemo Regimen. Regimens are as follows:
Regimen 1: Docetaxel 75 mg/m2 IV over 1 hour, day 1, followed by Cisplatin 75 mg/m2 IV over 1-2 hours, day 1,every 21 days. Prophylactic ciprofloxacin 500 mg twice daily, orally, on days 5-14. Regimen 1 carbo: Docetaxel 75 mg/m2 IV over 1 hour, day 1, followed by Carboplatin AUC 6 over 30 min., day 1, every 21 days. Prophylactic ciprofloxacin 500 mg twice daily, orally, on days 5-14. Regimen 2: Cisplatin 100 mg/m2 IV over 1-2 hours on day 1, followed by 5-FU 1000 mg/m2 /day as a continuous infusion x 4 days, every 21 days. Prophylactic ciprofloxacin 500 mg twice daily, orally, on days 5-14. Regimen 2 carbo: Carboplatin AUC 6 over 30 min., day 1, followed by 5-FU 1000 mg/m2 /day as a continuous infusion x 4 days, every 21 days. Prophylactic ciprofloxacin 500 mg twice daily, orally, on days 5-14. NOTE: Chemotherapy regimen choice will be at the discretion of the treating physician and will be made prior to randomization. NOTE: If maximum response, option to discontinue chemotherapy treatment after 6 cycles.
- 18 and older
Patients must have histologically or cytologically confirmed Squamous Cell Cancer of the Head and Neck (SCCHN), from any primary site, including unknown primary cancers of the head and neck. Patient must not have nasopharyngeal carcinoma of histologic types WHO 2 or 3 or squamous cell carcinoma that originated in the skin.
3.2 Patients must have SCCHN that is either (a) recurrent, judged incurable by surgery or radiation or (b) metastatic.
NOTE: Patients who refuse radical resection for recurrent disease are eligible
NOTE: A second primary squamous cell carcinoma of the head and neck is allowed if eligibility is based on a recurrent or metastatic first primary squamous cell carcinoma of the head and neck.
3.3 No prior chemotherapy or biologic/molecular targeted therapy for recurrent or metastatic SCCHN.
3.3.1 Patients may have received one regimen of induction, concomitant chemoradiotherapy and/or adjuvant chemotherapy as part of initial potential curative therapy but must not have received prior chemotherapy for recurrent or metastatic disease.
3.3.2 A minimum of 4 months is required between last dose of chemotherapy or chemoradiotherapy and study treatment. In addition patients must be progression-free for at least 4 months after completion of chemotherapy or chemoradiotherapy or radiation plus cetuximab given with a curative intent. (Cetuximab therapy: 4 months is required between last dose of chemotherapy or chemoradiotherapy and study treatment if part of concurrent regimen, 8 weeks if part of adjuvant regimen post radiation).
3.3.3 Patients having progression after 2 cycles of induction chemotherapy are not eligible for the study.
3.4 No prior bevacizumab is allowed
A maximum of one prior radiotherapy regimen, curative or palliative, to the head and neck is allowed. If the radiation is combined with chemotherapy and/or cetuximab, a minimum of 4 months must elapse between the end of radiotherapy and registration. If the radiation is given alone, a minimum of 8 weeks must elapse between the end of radiotherapy and registration. A minimum of 3 weeks must elapse between prior radiation to other areas and registration.
3.6 Patients must not be receiving any other investigational agent while on the study.
ECOG performance status of 0-1
3.8 Patients must have recovered to grade 1 or better from any acute effects of prior surgery, chemotherapy, or radiation therapy, and should be > 4 weeks post surgery. Chronic late xerostomia, speech and swallowing abnormalities resulting from prior radiation or surgery are permitted if nutritional status is stable.
3.9 Patients must have measurable disease based on RECIST (see Sec. 6.0). Baseline measurements and evaluations of all sites of disease must be obtained < 4 weeks prior to randomization. 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).
Hgb > 8.0
Creatinine C >60
No known brain metastases.
3.14 Patients who meet the following criteria will be excluded due to the possibility of increased risk for tumor bleeding with bevacizumab therapy:
3 history of gross hemoptysis (bright red blood of ½ teaspoon or more per episode of coughing) < 3 months prior to enrollment.
3.15 No history of coagulopathy or hemorrhagic disorders.
3.16 Patients should not have a history of thrombosis (e.g. pulmonary embolism or deep venous thrombosis) currently requiring therapeutic anticoagulation (prophylactic use of warfarin 1 mg per day is allowed) and INR should be < 1.5 at registration.
3.17 Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents (NSAID’s) known to inhibit platelet function. The use of anti-platelet agents (e.g. dipyridamole (Persatine), ticlopidine (Ticlid), clopidogrel (Plavix)) is allowed only if patient is not receiving aspirin or NSAID’s known to inhibit platelet function.
3.18 No hypercalcemia related to head and neck cancer.
3.19 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 3 years post diagnosis.
3.20 No current peripheral neuropathy > grade 2 at time of randomization.
3.21 Patients must not have any co-existing condition that would preclude full compliance with the study.
3.22 No prior history of severe hypersensitivity reaction to Docetaxel or other drugs formulated with polysorbate 80, if the physician’s choice of chemotherapy regimen is docetaxel.
3.23 All patients must have blood pressure < 150/90 < 2 weeks prior to randomization. Patients with history of hypertension must be well controlled (<150/90) on stable anti-hypertensive therapy
No major surgical procedure, open bx or significant traumatic injury less than 28 days prior to study enrollment (or anticipation of needing such during the course of the study)
- Eastern Cooperative Oncology Group
- Last Updated:
- Study HIC#:
Clinicaltrials.gov ID: Yale1942669