Study of Pemetrexed and Bevacizumab in Patients With Head and Neck Cancer
Condition: Cancer
MeSH terms: Head and Neck Neoplasms
Intervention: Pemetrexed; Bevacizumab
Intervention description: 500 mg/m2 day 1 q 21 days; 15 mg/kg IV q 21 days following pemetrexed
Intervention MeSH terms: Bevacizumab; Pemetrexed
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: head; neck

Summary:

      The purpose of this study is to determine if the combination of two new drugs pemetrexed
      (Alimta) and bevacizumab (Avastin) can increase the effectiveness of treatment for head and
      neck cancer. Currently pemetrexed is approved by the Food and Drug Administration (FDA) for
      another type of cancer, mesothelioma, but it is not approved for head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Metastatic or locally recurrent squamous cell carcinoma of the head and neck. Patients
             with local recurrence will be considered incurable by means of locoregional therapy,
             as judged by the investigator.

          2. Cytologically or histologically confirmed squamous cell carcinoma. Nasopharyngeal
             carcinoma of histologic subtype WHO II and III will be excluded.

          3. Unidimensional measurable disease (RECIST criteria). If the only site of measurable
             disease is in a previously irradiated area, the patient must have documented
             progression of disease in this area.

          4. ECOG performance status 0-1.

          5. Full recovered from the effects of any prior surgery, or radiation therapy. A minimum
             time period of 3 weeks will elapse between the completion of extensive radiation
             therapy for recurrent/metastatic disease and enrollment in the study

          6. Laboratory values:

             ANC ³ 1500/mm³. Platelets ³ 100,000/mm³. Total Bilirubin within normal institutional
             limits.

          7. Transaminases (AST and ALT) < 3 x ULN. Creatinine clearance 45 ml/min or higher
             calculated using the Cockcroft-Gault formula.

          8. Urine protein to creatinine (UPC) ratio of ≤ 1.0 on spot urine urinalysis.

          9. Age > 18 years and capacity to give informed consent.

        Exclusion Criteria:

          1. Prior chemotherapy or biologic therapy for recurrent/metastatic head and neck cancer.

          2. Prior pemetrexed, bevacizumab, or other antiangiogenesis agents at any time.

          3. Presence of tumors that invaded major vessels.

          4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment, or anticipation of need for major surgical procedure during
             the course of the study

          5. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to study enrollment.

          6. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to registration. Serious non-healing wound, ulcer, or bone
             fracture.

          7. History of brain metastasis or seizures.

          8. Prior malignancy, with the exception of curatively treated squamous cell or basal
             carcinoma of the skin or in situ cervical cancer, unless there is a 5-year
             disease-free interval.

          9. Pre-existing peripheral neuropathy > grade 2.

         10. Myocardial infarction or stroke in the last 6 months. Unstable angina; Heart
             Association (NYHA) Grade II or greater congestive heart failure; Clinically
             significant peripheral vascular disease; CNS cerebrovascular ischemia within the last
             6 months; active serious infection; other coexisting medical condition that would
             preclude full compliance with the study

         11. Bleeding diathesis or coagulopathy.

         12. Therapeutic anticoagulation (prophylactic use of warfarin 1 mg per day is allowed) or
             INR greater than 1.5 at registration

         13. History of gross hemoptysis (defined as bright red blood of a ½ teaspoon or more).

         14. Uncontrolled hypertension (>150/100)

         15. Pregnant or lactating.

         16. Use of NSAIDs within 5 days of protocol therapy.