Gemcitabine, Bevacizumab and Erlotinib in Pancreatic Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to learn whether or not the combination of gemcitabine, bevacizumab and erlotinib works in treating patients with advanced or metastatic pancreatic cancer. Bevacizumab is a new anti-cancer drug. It is an antibody that works to slow or stop cell growth in cancerous tumors by decreasing the blood supply to the tumors. It is approved by the FDA for the treatment of colorectal cancer but is still considered investigational for treating pancreatic cancer.

Detailed Description
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Participants will receive study treatment as an outpatient. The study treatment will be given in time periods called cycles. Each treatment cycle will be 28 days. Gemcitabine will be given intravenously on days 1, 8, and 15 (once per week for the first three weeks) of the treatment cycle. Bevacizumab will be given intravenously on days 1 and 15 (once every 2 weeks) of the treatment cycle. Erlotinib will be taken orally every day of the treatment cycle. Participants will see the doctor or nurse practitioner every week for the first 28 days of treatment. During all of the following cycles, they will see the doctor or nurse practitioner on day 1 and day 15 of each cycle. Each 4-week cycle can be repeated until the participant or the doctor decided that they should be removed from the study.

Official Title
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Phase II Study of Gemcitabine, Bevacizumab and Erlotinib in Locally Advanced and Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer, Adenocarcinoma of the Pancreas

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Erlotinib
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated patients with unresectable or metastatic adenocarcinoma of the pancreas ECOG Performance Status 0-2 18 years of age or older Radiographically measurable disease Expected survival of at least 4 months Creatinine of </= 2.0 Adequate hepatic function Adequate hematopoietic function Use of effective means of contraception in subjects of child-bearing potential Exclusion Criteria: Warfarin anticoagulation Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor Coexistent malignant disease Current or recent (within 4 weeks) participation in a clinical trial Pregnancy Documented invasion of adjacent organs or major blood vessels Blood pressure of > 150/100mmHg 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 of coagulopathy Presence of CNS or brain metastases Major surgical procedure, open biopsy, or significant traumatic event within 28 days Minor surgical procedures, fine needle aspirations or core biopsies within 7 days History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months Serious non-healing wound, ulcer or bone fracture

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Gemcitabine, Bevacizumab and Erlotinib<br>single-arm, no masking | Drug: Bevacizumab<br>* Given intravenously on days 1 and 25 of every 28-day cycle (one every 2 weeks). Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.<br>* Other names: rhuMAb VEGF;Drug: Erlotinib<br>* Taken orally every day. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.<br>* Other names: Tarceva;Drug: Gemcitabine<br>* Given intravenously on days 1, 8 and 15 of each 28-day cycle. Participants may continue to receive study treatment as long as there is no disease progression or serious side effects.<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tumor Progression | Time to tumor progression (TTP) = time from date of initial treatment to first objective documentation of progressive disease or death; patients who die without a reported prior progression will be considered to have progressed on the day of their death. 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. | all patients will be followed for a minimum of 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Response rate using RECIST criteria and latest time point available. 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. | after at least one 28-day cycle of treatment | 
| Toxicity Profile | Grade 3-4 treatment-related toxicities (treatment-related = possible, probable, or definite) Grading system: 1= mild, 2 = moderate, 3 = severe, 4 = life-threatening | during and after first 28-day cycle of treatment | 
| Overall Survival | overall survival (OS) = time from study entry until death from any cause | 5 years |