Gemcitabine and Erlotinib in Treating Patients With Metastatic or Recurrent Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with erlotinib may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with erlotinib works in treating patients with metastatic or recurrent pancreatic cancer.

Detailed Description
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OUTLINE: This is a multicenter study. Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15 and oral erlotinib hydrochloride on days 2-5, 9-12, and 16-26. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Archived tumor tissue samples are analyzed for the expression of EGFR, HER3, HER2, downstream signaling molecules, and other molecular markers by immunohistochemistry and RT-PCR. The presence of aberrant gene copy numbers (amplification and polysomy) for EGFR, HER3, and HER2 are determined by FISH. Blood samples are collected at baseline and periodically during study for polymorphism analysis and correlative molecular analysis of surrogate endpoint biomarkers. After completion of study therapy, patients are followed every 3 months.

Official Title
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Phase II Study of Gemcitabine and Intermittent Erlotinib in Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Erlotinib
* Drug: gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed locally advanced, metastatic or recurrent pancreatic carcinoma Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension No prior chemotherapy for metastatic or recurrent disease is allowed. Prior adjuvant chemotherapy is allowed provided that patients did not receive gemcitabine and the chemotherapy was completed > six months prior to initiation of study therapy. Prior erlotinib therapy is not allowed Available tumor specimen that was obtained at the time of diagnosis and/or prior to study entry is highly encouraged Age ≥ 18 years Life expectancy greater than 3 months Zubrod performance status ≤ 2 Patients must have normal organ and marrow function as defined below: leukocytes ≥ 3,000/μL absolute neutrophil count ≥ 1,500/ μL platelets ≥ 100,000/ μL total bilirubin ≤ 1.5 X institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤ 3 X institutional upper limit of normal, unless the liver is involved with tumor, in which case the AST/ALT must be ≤ 5 X institutional upper limit of normal creatinine clearance ≥ 50 mL/min/1.73 m2, as measured by 24hour collection OR creatinine ≤ 1.5 X institutional upper limit of normal The effects of erlotinib and gemcitabine on the developing human fetus at the recommended therapeutic doses are unknown. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients may not be receiving any other investigational agents. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib or gemcitabine. Secondary primary malignancy. Concurrent or history of another malignancy < 5 years. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women are excluded from this study because erlotinib and gemcitabine have the potential for teratogenic or abortifacient effects. Breastfeeding should be discontinued if the mother is treated with study drugs. Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy.

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 |
| --- | --- |
| Experimental: Gemcitabine and Erlotinib<br>The dose for gemcitabine is 1,000 mg/m2 administered over 30 minutes as an intravenous infusion. The doses are administered weekly for 3 weeks (Days 1, 8 and 15) followed by one week of rest during which gemcitabine is not given. This 4 week period (28 days) constitutes a cycle.Erlotinib will be dosed at 150mg orally (tablets) on days 2-5, 9-12, and 16-26 of a 28 day cycle. | Drug: Erlotinib<br>* Erlotinib will be administered at 150 mg once daily by mouth on the following schedule: days 2-5, 9-12,16-26.<br>* Other names: Tarceva;Drug: gemcitabine<br>* The dose for gemcitabine is 1,000 mg/m2 administered over 30 minutes as an intravenous infusion. The doses are administered weekly for 3 weeks (Days 1, 8 and 15) followed by one week of rest during which gemcitabine is not given. This 4 week period (28 days) constitutes a cycle.<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Defined as the time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. 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. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | 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. | Up to 36 months | 
| Overall Survival | Overall survival will be followed for survival every three months until documented progression, death or study termination. If a participant is still alive, survival time is censored at the time of last follow-up. | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent pancreatic cancer, stage IV pancreatic cancer