Clinical trial NCT01007552: A Study of Gemcitabine, Capecitabine and Bevacizumab to Treat Cancer of the Gall Bladder or Bile Ducts
Official title: A Multicenter Phase II Study of Gemcitabine, Capecitabine and Bevacizumab for Locally Advanced or Metastatic Adenocarcinoma of the Gall Bladder or Biliary Ducts.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cholangiocarcinoma
Keywords: Biliary Duct Cancer
Cancer of the Gallbladder
Adenocarcinoma of the Gall Bladder
Adenocarcinoma of the Biliary Ducts
Cholangiocarcinoma
Extrahepatic cholangiocarcinoma
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2009-11-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: 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.
timeFrame: 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
Secondary outcomes:
measure: Estimate the Proportion of Patients With Clinical Response
timeFrame: 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
measure: Assess the Toxicity of the Regimen.
timeFrame: up to 5 years
measure: Assess the Change in the Quality of Life Among Patients Using the FACT-Hep (Version 4) for Hepatobiliary Cancers.
timeFrame: Baseline, Day 22 and Day 43
measure: Assess Overall Survival (OS)
timeFrame: 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
measure: Circulating Tumor Cells (CTC) Will be Assessed at Baseline, Day 22 and Day 43
timeFrame: baseline, day 22 and day 43
measure: Collect Samples at Baseline, Day 8 and Day 43 for Future Biomarker Studies and Development of Profiles of Responders to Anti-VEGF Therapy (Optional)
timeFrame: Baseline, day 8 and day 43
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Roswell Park Cancer Institute
name: Renuka Iyer, MD
role: PRINCIPAL_INVESTIGATOR
References: