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

Primary Purpose

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
erlotinib
Sulindac
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck (SCCHN) focused on measuring SCCHN, erlotinib, tarceva

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Erlotinib + Bevacizumab

Erlotinib + Sulindac

Arm Description

erlotinib plus bevacizumab

erlotinib plus sulindac

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Duration of Overall Survival
Median overall survival (OS), determined by the Kaplan-Meier method.
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

Full Information

First Posted
October 24, 2006
Last Updated
March 15, 2017
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Emory University, University of North Carolina, Chapel Hill, Genentech, Inc., OSI Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00392665
Brief Title
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

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
October 2006 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Emory University, University of North Carolina, Chapel Hill, Genentech, Inc., OSI Pharmaceuticals

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Keywords
SCCHN, erlotinib, tarceva

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Erlotinib + Bevacizumab
Arm Type
Active Comparator
Arm Description
erlotinib plus bevacizumab
Arm Title
Erlotinib + Sulindac
Arm Type
Active Comparator
Arm Description
erlotinib plus sulindac
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Given intravenously on day one of each 3 week cycle
Intervention Type
Drug
Intervention Name(s)
erlotinib
Other Intervention Name(s)
Tarceva
Intervention Description
Given orally once a day
Intervention Type
Drug
Intervention Name(s)
Sulindac
Intervention Description
Given orally twice a day
Primary Outcome Measure Information:
Title
Efficacy of Erlotinib Plus Bevacizumab (Arm A) or Erlotinib Plus Sulindac (Arm B) as Measured by Progression-free Survival.
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
2 years
Title
Duration of Overall Survival
Description
Median overall survival (OS), determined by the Kaplan-Meier method.
Time Frame
2 years
Title
Number of Participants With Toxicities According to Severity
Description
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
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jochen Lorch, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

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

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