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.”

The primary objective of this study is to assess progression free survival with proposed therapy for patients with locally advanced or metastatic gallbladder and biliary cancers.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2012

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

• Estimate the proportion of patients with clinical response
  • Time Frame: 6/4/2012
    Safety Issue?: Yes

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 equal to or greater than 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 of greater than 3 months
• Patients must have normal organ and marrow function as defined below: leukocytes equaL to or greater than 3,000/microL absolute neutrophil count equal to or greater than 1,500/microL platelets equal to or greater than 1OO,OOO/microL total bilirubin less than or equal to 2 mg/dl AST or ALT less than or equal to 5 times upper limit of normal for subjects with documented liver metastases; less than or equal to 2.5 times the upper limit of normal for subjects without evidence of liver metastases.
• creatinine less than 1.5 mg/dL. Or 24 hour urine creatinine clearance greater than 50 ml/min.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrer 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.
• Patients 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 greater than or equal to 1.5 (except those subjects who are receiving full-dose warfarin)
• Hemoglobin of less than 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 less than 50 ml/min or urine protein / creatinine ratio greater than or equal to 1.0 at screening.
• Proteinuria at baseline or clinically significant impairment of renal function.
• 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 Sponsor: Roswell Park Cancer Institute

Overall Clinical Trial Officials and Contacts

Overall Contact: Renuka Iyer, MD 716-845-3099 renuka.iyer@roswellpark.org

Information obtained from ClinicalTrials.gov on February 04, 2010

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

Study ID Number: I 150509

ClinicalTrials.gov Identifier: NCT01007552

Health Authority: United States: Food and Drug Administration