A Phase II Study of Gemcitabine and Erlotinib As Adjuvant Therapy In Patients With Resected Pancreatic Cancer

Study Overview
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Brief Summary
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Study Hypothesis: To estimate time to recurrence in pancreatic cancer patients treated with adjuvant erlotinib and gemcitabine. Combination therapy will be given for 4 months followed by single agent erlotinib for a total of 12 months.

Detailed Description
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PATIENT POPULATION Resected pancreatic cancer patients (R0 resection) within 10 weeks of surgery will be eligible, provided that they meet standard eligibility criteria. STUDY DESIGN Phase II, open-label trial of erlotinib and gemcitabine. SAFETY PLAN Safety as assessed by CTCAE 3.0 STUDY TREATMENT Erlotinib 150 mg/day x 12 months. (oral) Gemcitabine 1500 mg/m2 IV over 150 minutes q 2 weeks x 4 months Patients will be monitored with serial CT scans for the first 2 years after completion of therapy. Clinical Practice: Therapy will be administered as an outpatient. Primary Evaluations: Time to recurrence CONCOMITANT THERAPY AND CLINICAL PRACTICE No other anti-cancer therapy will be allowed while on study.

Official Title
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A Phase II Study of Gemcitabine and Erlotinib As Adjuvant Therapy In Patients With Resected Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with potentially resectable pancreatic cancer (including ampullary cancer), prior to or after surgery will be accrued to this study. Patients who sign consent prior to surgery must have appropriate diagnostic imaging and be evaluated by one of the surgical co-investigators as having resectable disease, and probable pancreatic adenocarcinoma. Patients, who sign consent after surgery, must have adenocarcinoma of the pancreas with negative surgical margins. Adjuvant therapy should start within 10 weeks of surgery Age 18 years or older ECOG performance status of 0 - 1 (see Appendix A) Ability to take oral medications without difficulty Adequate bone marrow function as evidenced by an absolute neutrophil content (ANC) > 1500/mL and platelet count > 100,000/mL Adequate renal function as evidenced by serum creatinine within institutional limits or creatinine clearance > 50 ml/minute if above upper institutional limits (ULN) Adequate hepatic function as evidenced by ALT and total bilirubin within 2 times ULN. Provision of written informed consent. Men and women of childbearing potential must be willing to practice acceptable methods of birth control to prevent pregnancy. Exclusion Criteria: Positive margins on post operative surgical specimen or evidence of metastatic disease (positive retroperitoneal margin is allowed) Biliary tree cancers are not allowed (Note: Ampullary cancer allowed). Known severe hypersensitivity to erlotinib or any of the excipients of these products Any prior treatment with radiation therapy or chemotherapy or vaccines for pancreatic cancer. Other coexisting malignancies or malignancies diagnosed within the last 3 years, with the exception of basal cell carcinoma or squamous cell carcinoma of the skin or cervical cancer in situ. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St. John's Wort. Other agents which inhibit CYP3A4 may be used with caution (Appendix B) Treatment with a non-approved or investigational drug prior to treatment. Incomplete healing from previous oncologic or other major surgery. Pregnancy or breast feeding (women of childbearing potential). As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease). Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the subject to participate in the trial.

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>Erlotinib (oral) 150 mg/day x 12 months Gemcitabine 1500 mg/m2 IV over 150 minutes q 2 weeks x 4 months | Drug: Gemcitabine<br>* 1500mg/m2 IV over 150 min IV q 2 weeks 4 months<br>* Other names: Gemzar;Drug: Erlotinib<br>* 150 mg/d Daily, oral 12 months<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Free Survival (RFS) | The time interval between day 1, cycle 1, of adjuvant treatment to the first date of radiologic recurrence or death. | Up to 60 months | 
| 1-year Recurrence Free Survival (RFS) |  | Up to 60 months | 
| 2-year Recurrence Free Survival (RFS) |  | Up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated 1&2 Year Overall Survival (OS) | Time from from date of first study therapy to to death from any cause. | Up to 60 months | 
| Percentage of Participants With Expression of Epidermal Growth Factor Receptor (EGFR) | Percentage of participants with expression of epidermal growth factor receptor (EGFR) expression in the resected tumors was assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). | Up to 60 months | 
| KRAS Mutational Status | KRAS mutation status in resected tumor specimens. | Up to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreas, Cancer, Pancreatic