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Gemcitabine, Oxaliplatin in Combination With Bevacizumab in Biliary Tract and Gallbladder Cancer

Primary Purpose

Biliary Tract Cancer, Gallbladder Adenocarcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Gemcitabine
Oxaliplatin
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Biliary Tract Cancer focused on measuring Avastin, GEMOX

Eligibility Criteria

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

Inclusion Criteria: Histologically confirmed, locally unresectable or metastatic biliary tract or gallbladder adenocarcinoma. Patients must have at least one measurable lesion outside prior radiation field. Zero to one prior chemotherapy for biliary tract or gallbladder cancer Age > 18 years ECOG performance status 0-2 Life expectancy > 12 weeks Adequate organ and bone marrow function Exclusion Criteria: Chemotherapy within past 3 weeks of initiation of therapy Pregnant or lactating women Clinically apparent central nervous system metastases or carcinomatous meningitis Biliary obstruction with inadequate drainage and total bilirubin > 2.5 mg/dL Concurrent malignancy of any site, except limited basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix Uncontrolled serious medical or psychiatric illness Pre-existing peripheral neuropathy of grade 2 or greater severity according to the Common Terminology Criteria of the NCI (version 3.0) Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study Blood pressure of > 150/100 mmHg Unstable angina NYHA Grade II or greater congestive heart failure History of myocardial infarction or stroke within 6 months Clinically significant peripheral vascular disease Evidence of bleeding diathesis or coagulopathy Major surgical procedure, open biopsy, or significant traumatic injury with 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 Serious, non-healing wound, ulcer, or bone fracture

Sites / Locations

  • Massachusetts General Hospital Cancer Center
  • Dana Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bevacizumab, Gemcitabine, Oxaliplatin

Arm Description

The chemotherapy drugs are given twice every 28 days. This 28 day period is called a cycle of study treatment. Bevacizumab will be administered by IV over 90 minutes on day 1 and day 15. Gemcitabine will be administered by IV over 1 hour and 40 minutes on days 1 and 15 of each cycle. Oxaliplatin will be administered by IV for 2 hours on days 1 and 15 of each cycle. Participants will continue to receive cycles of study treatment as long as their disease does not progress and they are not experiencing any serious side effects.

Outcomes

Primary Outcome Measures

Median Progression Free Survival
To assess the median progression free survival in patients with BTC on GEMOX-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. In addition, death in the absence of radiological disease progression was also categorized as progression.

Secondary Outcome Measures

Overall Response Rate
To assess the overall response rate of GEMOX-B in patients with advanced BTC. Response rate is determined through 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.

Full Information

First Posted
August 4, 2006
Last Updated
December 14, 2016
Sponsor
Massachusetts General Hospital
Collaborators
Genentech, Inc., Sanofi, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00361231
Brief Title
Gemcitabine, Oxaliplatin in Combination With Bevacizumab in Biliary Tract and Gallbladder Cancer
Official Title
Phase II Study of Gemcitabine, Oxaliplatin in Combination With Bevacizumab (Avastin) in Unresectable or Metastatic Biliary Tract and Gallbladder Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Genentech, Inc., Sanofi, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Dana-Farber Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purposes of this study are to test the safety of bevacizumab when given in combination with gemcitabine and oxaliplatin and to see what effects (good and bad) this combination has on patients with cancer of bile duct or gallbladder. Bevacizumab has been shown to slow or stop cell growth in tumors by decreasing the blood supply to the tumors.
Detailed Description
The chemotherapy drugs are given twice every 28 days. This 28 day period is called a cycle of study treatment. Bevacizumab will be administered by IV over 90 minutes on day 1 and day 15. Gemcitabine will be administered by IV over 1 hour and 40 minutes on days 1 and 15 of each cycle. Oxaliplatin will be administered by IV for 2 hours on days 1 and 15 of each cycle. The following tests and procedures will be performed on day 1 and day 15 or each cycle: physical examination; medical history; blood work; and urine test. A PET scan will be repeated at the end of cycle 2 and CT scans will be repeated once every 8 weeks. Participants will continue to receive cycles of study treatment as long as their disease does not progress and they are not experiencing any serious side effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Biliary Tract Cancer, Gallbladder Adenocarcinoma
Keywords
Avastin, GEMOX

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab, Gemcitabine, Oxaliplatin
Arm Type
Experimental
Arm Description
The chemotherapy drugs are given twice every 28 days. This 28 day period is called a cycle of study treatment. Bevacizumab will be administered by IV over 90 minutes on day 1 and day 15. Gemcitabine will be administered by IV over 1 hour and 40 minutes on days 1 and 15 of each cycle. Oxaliplatin will be administered by IV for 2 hours on days 1 and 15 of each cycle. Participants will continue to receive cycles of study treatment as long as their disease does not progress and they are not experiencing any serious side effects.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Given intravenously on days 1 and 15 of each 28-day cycle. Participants may continue to receive study treatment as lond as their disease does not progress and they do not experience any serious side effects.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Given intravenously on days 1 and 15 of each 28-day cycle. Participants may continue to receive study treatment as lond as their disease does not progress and they do not experience any serious side effects.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
Given intravenously on days 1 and 15 of each 28-day cycle. Participants may continue to receive study treatment as lond as their disease does not progress and they do not experience any serious side effects.
Primary Outcome Measure Information:
Title
Median Progression Free Survival
Description
To assess the median progression free survival in patients with BTC on GEMOX-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. In addition, death in the absence of radiological disease progression was also categorized as progression.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
To assess the overall response rate of GEMOX-B in patients with advanced BTC. Response rate is determined through 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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed, locally unresectable or metastatic biliary tract or gallbladder adenocarcinoma. Patients must have at least one measurable lesion outside prior radiation field. Zero to one prior chemotherapy for biliary tract or gallbladder cancer Age > 18 years ECOG performance status 0-2 Life expectancy > 12 weeks Adequate organ and bone marrow function Exclusion Criteria: Chemotherapy within past 3 weeks of initiation of therapy Pregnant or lactating women Clinically apparent central nervous system metastases or carcinomatous meningitis Biliary obstruction with inadequate drainage and total bilirubin > 2.5 mg/dL Concurrent malignancy of any site, except limited basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix Uncontrolled serious medical or psychiatric illness Pre-existing peripheral neuropathy of grade 2 or greater severity according to the Common Terminology Criteria of the NCI (version 3.0) Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study Blood pressure of > 150/100 mmHg Unstable angina NYHA Grade II or greater congestive heart failure History of myocardial infarction or stroke within 6 months Clinically significant peripheral vascular disease Evidence of bleeding diathesis or coagulopathy Major surgical procedure, open biopsy, or significant traumatic injury with 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 Serious, non-healing wound, ulcer, or bone fracture
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew X. Zhu, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25794066
Citation
Sahani DV, Hayano K, Galluzzo A, Zhu AX. Measuring treatment response to systemic therapy and predicting outcome in biliary tract cancer: comparing tumor size, volume, density, and metabolism. AJR Am J Roentgenol. 2015 Apr;204(4):776-81. doi: 10.2214/AJR.14.13223.
Results Reference
derived
PubMed Identifier
19932054
Citation
Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, Zheng H, Clark JW, Abrams TA, Chan JA, Enzinger PC, Bhargava P, Kwak EL, Allen JN, Jain SR, Stuart K, Horgan K, Sheehan S, Fuchs CS, Ryan DP, Sahani DV. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol. 2010 Jan;11(1):48-54. doi: 10.1016/S1470-2045(09)70333-X. Epub 2009 Nov 20.
Results Reference
derived

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Gemcitabine, Oxaliplatin in Combination With Bevacizumab in Biliary Tract and Gallbladder Cancer

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