Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck - Full Text View

Sponsors and Collaborators:	Massachusetts General Hospital Dana-Farber Cancer Institute Emory University The University of North Carolina, Chapel Hill Genentech OSI Pharmaceuticals
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00392665

Purpose

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 II

MedlinePlus related topics: Cancer

Drug Information available for: Sulindac Erlotinib hydrochloride Erlotinib Bevacizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Randomized Study of Bevacizumab/Tarceva and Tarceva/Sulindac in Squamous Cell Carcinoma of the Head and Neck

Further study details as provided by Dana-Farber Cancer Institute:

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 ]

Estimated Enrollment:	82
Study Start Date:	October 2006
Estimated Study Completion Date:	October 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm A: Active Comparator erlotinib plus bevacizumab	Drug: Bevacizumab Given intravenously on day one of each 3 week cycle Drug: erlotinib Given orally once a day
Arm B: Active Comparator erlotinib plus sulindac	Drug: erlotinib Given orally once a day 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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00392665

Contacts

Contact: Lori J Wirth, MD	617-726-2000	lwirth@partners.org
Contact: Maja Niemierko	617-643-4971	mniemierko@partners.org

Locations

United States, Georgia
Winship Cancer Institute	Recruiting
Atlanta, Georgia, United States, 30305
Contact: Nabil Saba, MD 404-686-8876 NFSABA@emory.edu
United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Rafia Khan 617-582-8013 rafia_khan@dfci.harvard.edu
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Lori J Wirth, MD 617-726-2000
United States, North Carolina
University of North Carolina at Chapel Hill	Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: David Neil Hayes, MD 919-966-3786 hayes@med.unc.edu

Sponsors and Collaborators

Massachusetts General Hospital

Dana-Farber Cancer Institute

Emory University

The University of North Carolina, Chapel Hill

Genentech

OSI Pharmaceuticals

Investigators

Principal Investigator:

Jochen Lorch, MD

Dana-Farber Cancer Institute

More Information

No publications provided

Responsible Party:	Dana-Farber Cancer Institute ( Jochen Lorch, MD )
Study ID Numbers:	06-111
Study First Received:	October 24, 2006
Last Updated:	February 10, 2009
ClinicalTrials.gov Identifier:	NCT00392665 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

SCCHN
erlotinib
tarceva

Study placed in the following topic categories:

Erlotinib
Anti-Inflammatory Agents
Cyclooxygenase Inhibitors
Carcinoma, Squamous Cell of Head and Neck
Bevacizumab
Squamous Cell Carcinoma
Protein Kinase Inhibitors
Angiogenesis Inhibitors
Carcinoma
Analgesics, Non-Narcotic

Epidermoid Carcinoma
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Neoplasms, Squamous Cell
Sulindac
Antirheumatic Agents
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Protein Kinase Inhibitors
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Growth Inhibitors
Angiogenesis Modulating Agents
Neoplasms, Squamous Cell
Analgesics
Erlotinib
Neoplasms by Histologic Type

Growth Substances
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Analgesics, Non-Narcotic
Sulindac
Peripheral Nervous System Agents
Carcinoma, Squamous Cell
Antirheumatic Agents
Central Nervous System Agents
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009