Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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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.

Detailed Description
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Participants will be randomized to either Arm A: erlotinib plus bevacizumab, or Arm B: erlotinib plus sulindac. Participants will have an equal chance of being placed in any group. Medication on Arm A: erlotinib plus bevacizumab: Participants will take erlotinib pills orally once a day. Bevacizumab will be given intravenously on day one of each treatment cycle (each treatment cycle will last three weeks). Urine tests will be performed once every three weeks to test kidney function. Medication on Arm B: erlotinib plus sulindac: Participants will take erlotinib pills orally once a day. Sulindac will be taken orally twice a day. Physical exams will be performed during each treatment cycle and will include vital signs and general health questions. We will take the participants blood pressure every 2 weeks for the first 6 weeks. After that point, we will take it every 3 weeks or more often if necessary. Blood tests will be performed including chemistry and hematology. After every 2 cycles, a repeat CT scan, MRI, and/or PET scan will be performed along with either a chest x-ray or CT scan to ensure that there is no tumor in the participants lungs. We may also do a bone scan if there may be tumor in the participants bones, and abdominal CT scan if there may be tumor in the liver, and a head CT scan or MRI if there may be tumor in the brain. After the final treatment the participant will be seen in the clinic to see if they have had any side effects from the drugs within 30 days of stopping the drugs. Participants will be in this research study for as long as they are receiving clinical benefits from the study drugs, and do not develop excessive side effects or disease progression. After treatment is discontinued, we will follow the participant closely for 30 days and every 1-2 months after that.

Official Title
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Randomized Study of Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: erlotinib
* Drug: Sulindac


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Erlotinib + Bevacizumab<br>erlotinib plus bevacizumab | Drug: Bevacizumab<br>* Given intravenously on day one of each 3 week cycle<br>Drug: erlotinib<br>* Given orally once a day<br>* Other names: Tarceva;|
| Active Comparator: Erlotinib + Sulindac<br>erlotinib plus sulindac | Drug: erlotinib<br>* Given orally once a day<br>* Other names: Tarceva;Drug: Sulindac<br>* Given orally twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Erlotinib Plus Bevacizumab (Arm A) or Erlotinib Plus Sulindac (Arm B) as Measured by Progression-free Survival. | The primary outcome will be measured by median progression-free survival (PFS), determined by the Kaplan-Meier method for both Arm A and Arm B. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate (complete plus partial response=ORR), as determined by RECIST. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 2 years | 
| Duration of Overall Survival | Median overall survival (OS), determined by the Kaplan-Meier method. | 2 years | 
| Number of Participants With Toxicities According to Severity | Toxicities by Grades 1 or 2 and Grades 3 or 4 in each arm. Grade 4 = life-threatening, Grade 3 = serious, Grade 2 = moderate, Grade 1 = Mild | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCCHN, erlotinib, tarceva