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

This study has been completed.
Dana-Farber Cancer Institute
Emory University
University of North Carolina, Chapel Hill
Genentech, Inc.
OSI Pharmaceuticals
Information provided by (Responsible Party):
Lori J. Wirth, MD, Massachusetts General Hospital Identifier:
First received: October 24, 2006
Last updated: April 12, 2016
Last verified: April 2016
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.

Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Drug: Bevacizumab
Drug: erlotinib
Drug: Sulindac
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Study of Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • To evaluate the efficacy of erlotinib plus bevacizumab (Arm A) or erlotinib plus sulindac (Arm B) in subjects with incurable recurrent and/or metastatic squamous cell carcinoma of the head and neck as measured by progression-free survival. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate overall response rate, duration of overall survival and objective response rate of these treatment regimens in this patient population [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • to evaluate the safety of these treatment regimens in this patient population. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: October 2006
Study Completion Date: December 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
erlotinib plus bevacizumab
Drug: Bevacizumab
Given intravenously on day one of each 3 week cycle
Drug: erlotinib
Given orally once a day
Other Name: Tarceva
Active Comparator: Arm B
erlotinib plus sulindac
Drug: erlotinib
Given orally once a day
Other Name: Tarceva
Drug: Sulindac
Given orally twice a day

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.

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

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00392665

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Emory University
University of North Carolina, Chapel Hill
Genentech, Inc.
OSI Pharmaceuticals
Principal Investigator: Jochen Lorch, MD Dana-Farber Cancer Institute
  More Information

Responsible Party: Lori J. Wirth, MD, Principal Investigator, Massachusetts General Hospital Identifier: NCT00392665     History of Changes
Other Study ID Numbers: 06-111 
Study First Received: October 24, 2006
Last Updated: April 12, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Erlotinib Hydrochloride
Analgesics, Non-Narcotic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Sensory System Agents processed this record on May 26, 2016