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Title   A Phase III Randomized Trial of Chemotherapy with or without Bevacizumab in Patients with Recurrent Or Metastatic Head and Neck Cancer
Study Number   E1305
Trial Type   Oncology-Head and Neck
Condition   -
Trial Status   Open to Accrual
Date Posted   09/05/2012
Principal Investigator   Marshall Levine¸ MD
Contact Name   Jennifer Lippy
Phone   (443) 849-8089
Alternate Phone   (443) 849-8058
Fax   (443) 849-3777
Description  

OUTLINE: This is a multicenter study. Patients are stratified by performance status (0 vs 1), weight loss (< 5% vs ≥ 5% of total body weight in the past 6 months), prior radiotherapy to head and neck (yes vs no), and chemotherapy regimen (cisplatin/docetaxel vs cisplatin/fluorouracil). Patients are randomized to 1 of 2 treatment arms.



  • Arm A (chemotherapy): Patients receive chemotherapy (one of 4 doublets, including either docetaxel + cisplatin, docetaxel + carboplatin, cisplatin + fluorouracil or carboplatin + fluorouracil). Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity*.

  • Arm B (chemotherapy and bevacizumab): Patients receive chemotherapy as in arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment with chemotherapy and bevacizumab repeats every 21 days in the absence of disease progression or unacceptable toxicity*.


NOTE: *Treatment with chemotherapy may be discontinued if there is maximum response (i.e., no improvement in tumor measurements for 2 or more courses) after course 6; bevacizumab administration continues until disease progression in arm II.


After completion of study treatment, patients are followed every 3-6 months for 5 years.

Inclusion/Notes  

Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed squamous cell carcinoma of the head and neck (SCCHN) from any primary site, including unknown primary cancers of the head and neck

    • No nasopharyngeal carcinoma of histologic types WHO 2 or 3
    • No squamous cell carcinoma that originated in the skin
  • Recurrent disease, incurable disease as determined by surgery or radiation, or metastatic disease

    • A second primary squamous cell carcinoma of the head and neck allowed if eligibility is based on a recurrent or metastatic first primary squamous cell carcinoma of the head and neck
  • Patients who refuse radical resection for recurrent disease are eligible
  • Patients must have measurable disease based on RECIST

    • Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma after radiotherapy
    • Persistent disease after radiotherapy must be biopsy proven at least 8 weeks after completion of radiotherapy (radiographic findings are acceptable providing that clearcut measurements can be made)
  • Patients must be progression-free for at least 6 months after completion of chemotherapy or chemoradiotherapy or radiotherapy plus cetuximab given as part of initial potential curative therapy (if received such prior therapy)

    • At least 6 months since completion of prior concurrent radiotherapy plus cetuximab (8 weeks for cetuximab given as part of adjuvant regimen post radiotherapy)
    • Patients having progression after 2 courses of induction chemotherapy are not eligible
  • No tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies (i.e., tumor crosses fat boundary)
  • No central (i.e., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies
  • No known brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • ANC ≥ 1,500/mm^3
  • Hemoglobin ≥ 8.0 g/dL
  • Platelet count ≥ 100,000/mm^3
  • Creatinine clearance ≥ 60 mL/min
  • Total bilirubin normal
  • AST or ALT and alkaline phosphatase must meet one of the following criteria:

    • Alkaline phosphatase normal AND AST or ALT ≤ 5 x upper limit of normal (ULN)
    • Alkaline phosphatase > 1 but ≤ 2.5 x ULN AND AST or ALT > 1 but ≤ 1.5 x ULN
    • Alkaline phosphatase > 2.5 but ≤ 5 x ULN AND AST or ALT normal
  • Urine protein:creatinine ratio ≤ 0.5 OR 24-hour urine protein < 1,000 mg
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients who meet the following criteria are excluded:

    • Any prior history of bleeding related to the current head and neck cancer
    • History of gross hemoptysis (bright red blood of ½ teaspoon or more per episode of coughing) ≤ 3 months prior to enrollment
  • No history of coagulopathy or hemorrhagic disorders
  • No history of thrombosis (e.g., pulmonary embolism or deep venous thrombosis) currently requiring therapeutic anticoagulation (prophylactic use of warfarin 1 mg/day is allowed)
  • INR < 1.5 at registration
  • No hypercalcemia related to head and neck cancer
  • Patients with a prior history of squamous cell or basal cell carcinoma of the skin or in situ carcinoma of the cervix 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
  • Patients must not have any co-existing condition that would preclude full compliance with the study
  • No history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 (if the physician's choice of chemotherapy is docetaxel)
  • Patients must have a blood pressure (BP) ≤ 150/90 within 2 weeks prior to randomization

    • Patients with a history of hypertension must be well-controlled upon study entry (BP ≤ 150/90 mm Hg) on a stable regimen of anti-hypertensive therapy
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration
  • No significant traumatic injury within the past 28 days
  • No serious nonhealing wound, ulcer, or bone fracture
  • No unstable angina or myocardial infarction within the past 6 months
  • No symptomatic congestive heart failure or New York Heart Association (NYHA) class II-IV heart disease
  • No history of aortic dissection or presence of aneurysm > 6 cm (or at high risk for rupture)
  • No serious cardiac arrhythmia requiring medication (history of chronic atrial fibrillation or other atrial arrhythmia with controlled rate on medication is allowed)
  • No clinically significant peripheral vascular disease manifested by intermittent claudication or need for vascular intervention
  • No history of any CNS cerebrovascular ischemia or stroke within the past 6 months
  • No active serious infection
  • No history of a serious human anti-human antibody (HAHA) reaction
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible
  • Chronic late xerostomia, speech and swallowing abnormalities, resulting from prior radiation or surgery, allowed provided nutritional status is stable
  • No other prior malignancy except curatively treated squamous cell or basal carcinoma of the skin, in situ cervical cancer, or malignancy for which the patient has been curatively treated and remains disease-free for the past 3 years

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Patients must have recovered to grade 1 or better from the effects of any prior surgery, chemotherapy, or radiotherapy AND > 4 weeks post-surgery
  • No more than one prior radiotherapy regimen, curative or palliative, to the head and neck allowed

    • At least 4 months since prior radiotherapy in combination with chemotherapy and/or cetuximab
    • At least 8 weeks since prior radiotherapy given alone
  • At least 3 weeks since prior radiotherapy to other areas
  • No prior bevacizumab
  • No prior chemotherapy or biologic/molecular-targeted therapy for recurrent or metastatic SCCHN

    • Patients may have received one regimen of induction, concurrent chemoradiotherapy, and/or adjuvant chemotherapy as part of initial potential curative therapy

      • A minimum of 6 months is required between last dose of chemotherapy or chemoradiotherapy and study treatment
  • No major surgical procedure or open biopsy within 28 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study
  • More than 4 weeks since prior surgery
  • No other concurrent investigational agent
  • Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents (NSAIDs) known to inhibit platelet function

    • The use of anti-platelet agents (e.g., dipyridamole [Persatine], ticlopidine [Ticlid], or clopidogrel [Plavix]) is allowed only if patient is not receiving aspirin or NSAIDs known to inhibit platelet function
  • No HIV-positive patients on combination antiretroviral therapy
  • No other concurrent chemotherapy, immunotherapy, antitumor hormonal therapy (excluding contraceptives and replacement steroids), radiotherapy, or experimental medications
  • No concurrent amifostine
  • No concurrent bisphosphonates for bone metastasis unless initiated > 3 months before study entry
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