Clinical trial NCT00392665: Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck
Official title: Randomized Study of Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Keywords: SCCHN
erlotinib
tarceva
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
name: Emory University
name: University of North Carolina, Chapel Hill
name: Genentech, Inc.
name: OSI Pharmaceuticals
First posted: 2006-10-26
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: * 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.

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

Primary outcomes:
measure: Efficacy of Erlotinib Plus Bevacizumab (Arm A) or Erlotinib Plus Sulindac (Arm B) as Measured by Progression-free Survival.
timeFrame: 1 year
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 2 years
measure: Duration of Overall Survival
timeFrame: 2 years
measure: Number of Participants With Toxicities According to Severity
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Jochen Lorch, MD
role: PRINCIPAL_INVESTIGATOR
References: