Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck
Condition: Squamous Cell Carcinoma of the Head and Neck (SCCHN)
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Bevacizumab; erlotinib; Sulindac
Intervention description: Given intravenously on day one of each 3 week cycle; Given orally once a day; Given orally twice a day
Intervention MeSH terms: Sulindac; Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SCCHN; erlotinib; tarceva

Summary:

      The main purpose of this research study is to collect information to learn how effective
      erlotinib (tarceva) is in combination with either bevacizumab or sulindac in treating
      patients with squamous cell carcinoma of the head and neck. Erlotinib and bevacizumab are
      targeted therapy drugs that can control tumor growth by targeting specific abnormalities
      sometimes found on cancer cells. Erlotinib targets epidermal growth factor receptor (EGFR),
      and bevacizumab targets vascular endothelial growth factor (VEGF). Sulindac is a
      non-steroidal anti-inflammatory drug (NSAID) that can block G protein-coupled receptor which
      laboratory evidence shows is associated with both cancer cell growth and EGFR activity. The
      bevacizumab being administered in this study is not a commercially marketed formulation of
      the drug. Previous research with head and neck cancer suggest that erlotinib alone has some
      anti-cancer activity. This research study is designed to see how well erlotinib works in
      combination with bevacizumab or sulindac in head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically/cytologically documented SCCHN, excluding salivary gland primary sites

          -  18 years of age or older

          -  Have evaluable locoregional and/or metastatic disease according to RECIST that is not
             appropriate for treatment by primary surgical resection or radiotherapy

          -  Have locoregional and/or metastatic disease that has failed to respond to or relapsed
             from at least one prior chemotherapy or chemoradiotherapy

          -  Life expectancy of at least 4 months

          -  ECOG performance status of 0-2

          -  Use of effective means of contraception in patients of child-bearing potential

        Exclusion Criteria:

          -  Other malignancy within 5 years except non-melanomatous skin cancer, or carcinoma in
             situ of the cervix, bladder or head and neck

          -  Concurrent anticancer therapy other than that of this study

          -  Treatment with any anticancer drug within 28 days of day 1

          -  Radiotherapy within 28 days of day 1

          -  Any unresolved toxicity greater than NCI-CTCAE v 3.0 grade 2 from prior systemic
             anticancer therapy

          -  Any prior therapy that targets the ErbB and/or VEGF pathways

          -  Concurrent therapy with any NSAID

          -  Known hypersensitivity characterized by acute bronchospasm, urticaria and/or rhinitis
             to NSAIDs, including aspirin

          -  Serum creatinine > 1.5 x ULN

          -  Abnormal LFTs as outlined in protocol

          -  Blood pressure > 150/100mmHg

          -  Active unstable angina, or myocardial infarction within 6 months

          -  NYHA Grade II or greater congestive heart failure

          -  History of stroke within 6 months

          -  Clinically significant active peripheral vascular disease

          -  Absolute neutrophil count < 1000/mm3 or platelets < 100,000/mm3

          -  Evidence of bleeding diathesis or coagulopathy.

          -  Tumor encasing the carotid artery, or other major vessel that in the opinion of the
             investigators is at risk for tumor-related hemorrhage

          -  Presence of central nervous system or brain metastases

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 1, or anticipation of need for major surgical procedure during the course
             of the study

          -  Minor surgical procedures such as fine needle aspiration or core biopsy within 5 days
             prior to day 1

          -  Pregnant or lactating

          -  History of abdominal fistula or intra-abdominal abscess within 6 months

          -  History of gastrointestinal ulcer, perforation, or bleeding within 6 months

          -  Serious non-healing wound or ulcer or active uncontrolled infection

          -  Bone fracture within 28 days

          -  Active substance abuse, defined by substance abuse of alcohol, cocaine or intravenous
             drug use within 6 months