A Study of Gemcitabine, Capecitabine and Bevacizumab to Treat Cancer of the Gall Bladder or Bile Ducts

Phase 2

Completed

Conditions: Cholangiocarcinoma

Interventions: Drug: Gemcitabine, Capecitabine and Bevacizumab

Registration Number: NCT01007552

Lead Sponsor: Roswell Park Cancer Institute

Brief Summary: To assess the proposed therapy for patients with advanced gallbladder or biliary cancers.

Detailed Description: The primary objective of this study is to assess progression free survival with proposed therapy for patients with locally advanced or metastatic adenocarcinoma of the gallbladder or biliary ducts.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

Inclusion Criteria

Patients must have histologically or cytologically confirmed gallbladder or biliary tract adenocarcinoma that is unresectable or metastatic, or metastatic adenocarcinoma which is radiologically confirmed to be of gallbladder or biliary origin. No prior systemic therapy for metastatic disease. Prior adjuvant therapy is permitted if completed over 6months ago.
Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of bevacizumab in combination with gemcitabine in patients over 18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.
ECOG performance status 0 or 1.
Life expectancy > 3 months.
Patients must have normal organ and marrow function as defined below:
- leukocytes ≥ 3,000/microL
- absolute neutrophil count ≥ 1,500/microL
- platelets ≥ 1OO,OOO/microL
- total bilirubin ≤ 2 mg/dl
- AST or ALT ≤ 5 times upper limit of normal (UNL) for subjects with documented liver metastases; ≤ 2.5 times UNL for subjects without evidence of liver metastases.
- creatinine < 1.5 mg/dL or 24 hour urine creatinine clearance > 50 ml/min.
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Signed, written informed consent document.
Patient must have measurable disease

Exclusion Criteria

Subjects meeting any of the following criteria are ineligible for study entry:
Compromised renal or hepatic function.
Screening clinical laboratory values INR ≥ 1.5 (except those subjects who are receiving full-dose warfarin)
Hemoglobin < 9 gm/dL (may be transfused or receive epoetin alfa (e.g., Epogen@) to maintain or exceed this level).
Bevacizumab risk factors: History of serious systemic disease, including uncontrolled hypertension (blood pressure of greater than 160/110 mmHg on medication), prior history of hypertensive crisis or hypertensive encephalopathy, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or clinically significant peripheral vascular disease (Grade II or greater).
Presence of central nervous system or brain metastases.
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day O.
Pregnancy (positive pregnancy test) or lactation.
24 hour urine creatinine clearance < 50 ml/min or urine protein/creatinine ratio greater than or equal to 1.0 at screening.
Serious, nonhealing wound, ulcer, or bone fracture.
Evidence of bleeding diathesis or coagu1opathy.
Recent (less than or equal to six months) arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI).
Inability to comply with study and/or follow-up procedures.
Patients with known duodenal or gastric wall involvement should be excluded.
Patients with suspected involvement of stomach or duodenum should have screening endoscopies to exclude the same prior to therapy.
Patients with esophageal or gastric varices.
Patients with recent hemoptysis (within 1 week).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gemcitabine, Capecitabine and Bevacizumab	Gemcitabine, Capecitabine and Bevacizumab	Estimate the toxicity of the regimen, and estimate the quality of life (QOL).

Primary Outcome Measures

Name	Time	Method
The Primary Objective of This Study is to Assess Progression Free Survival (PFS) With Proposed Therapy for Patients With Locally Advanced or Metastatic Gallbladder and Biliary Cancers.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years	Progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST 1.0). Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Note: Lesions are either measurable or non-measurable using the criteria provided below. The term "evaluable" in reference to measurability will not be used because it does not provide additional meaning or accuracy.

Secondary Outcome Measures

Name	Time	Method
Assess the Toxicity of the Regimen.	up to 5 years	Number of patients with Serious Adverse Events. Please refer to the adverse event reporting for more detail.
Estimate the Proportion of Patients With Clinical Response	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years	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.
Assess the Change in the Quality of Life Among Patients Using the FACT-Hep (Version 4) for Hepatobiliary Cancers.	Baseline, Day 22 and Day 43	We utilized the FACT-HEP TOTAL SCORE (version 4) quality-of-life scale, which is a 45 item scale ranging from 96-178. Higher scores of the reflect better quality of life. For a Detailed description see: Nancy Heffernan, David Cella, Kimberly Webster, Linda Odom, Mary Martone, Steven Passik, Marilyn Bookbinder, Yuman Fong, William Jarnagin, and Leslie Blumgart: Measuring Health-Related Quality of Life in Patients With Hepatobiliary Cancers: The Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire. Journal of Clinical Oncology, Vol 20, No 9 (May 1), 2002: pp 2229-2239. No subscales were analyzed. .
Assess Overall Survival (OS)	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
Circulating Tumor Cells (CTC) Will be Assessed at Baseline, Day 22 and Day 43	baseline, day 22 and day 43	Mean number of CTCs in 7.5 ml of whole blood
Collect Samples at Baseline, Day 8 and Day 43 for Future Biomarker Studies and Development of Profiles of Responders to Anti-VEGF Therapy (Optional)	Baseline, day 8 and day 43	This was a tissue banking end point of sample collection for future studies. No analysis was completed.

Trial Locations

Locations (2): Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States