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.”

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

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.

Intervention(s) in this Clinical Trial

• Drug: Gemcitabine, Capecitabine and Bevacizumab
  • Bevacizumab 15 mg/ kg every 3 weeks, starting day 1; Capecitabine 650 mg/m2 bid x 14 days starting day 1, Gemcitabine 1000 mg/m2 days 1 and 8, cycles to be repeated every 21 days.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Gemcitabine, Capecitabine and Bevacizumab
  • Estimate the toxicity of the regimen, and estimate the quality of life (QOL).

Primary Measures

• 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.
  • Time Frame: every 9 weeks
    Safety Issue?: Yes

Secondary Measures

• Estimate the proportion of patients with clinical response
  • Time Frame: 4 months
    Safety Issue?: No
• Assess the toxicity of the regimen.
  • Time Frame: Daily while on treatment
    Safety Issue?: Yes
• Assess the change in the quality of life among patients using the FACT HEp for hepatobiliary cancers.
  • Time Frame: Day 1 of every cycle
    Safety Issue?: No
• Assess overall survival (OS)
  • Time Frame: Every 2-4 months for one year and every 6 months after until death
    Safety Issue?: No
• Circulating tumor cells (CTC) will be assessed at baseline, day 22 and day 43 and then correlated with clinical outcomes.
  • Time Frame: baseline, day 22 and day 43
    Safety Issue?: No
• Collect samples at baseline, day 8 and day 43 for future biomarker studies and development of profiles of responders to anti-VEGF therapy
  • Time Frame: Baseline, day 8 and day 43
    Safety Issue?: No

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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Roswell Park Cancer Institute Other

Overall Clinical Trial Officials and Contacts

Renuka Iyer, MD Principal Investigator Roswell Park Cancer Institute  

Overall Contact: AskRPCI 1-877-275-7724 AskRPCI@roswellpark.org

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01007552

Study ID Number: RPCI I 150509

ClinicalTrials.gov Identifier: NCT01007552

Health Authority: United States: Food and Drug Administration