Combination Chemotherapy Plus Radiation Therapy With or Without Tipifarnib in Treating Patients With Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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Randomized phase II trial to compare the effectiveness of gemcitabine, paclitaxel, and radiation therapy with or without tipifarnib in treating patients who have locally advanced pancreatic cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining chemotherapy and radiation therapy with tipifarnib may be an effective treatment for pancreatic cancer.

Detailed Description
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OBJECTIVES: I. Compare the 1-year survival rate in patients with locally advanced pancreatic cancer treated with paclitaxel, gemcitabine, and radiotherapy with or without tipifarnib. II. Determine the toxicity and loco-regional activity of this chemoradiotherapy regimen in these patients. III. Determine the feasibility and toxicity of prolonged administration of tipifarnib after chemoradiotherapy in these patients. IV. Determine whether tipifarnib administered after chemoradiotherapy can increase progression-free and overall survival in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to weight loss in the preceding 6 months (more than 10% vs 10% or less) and tumor dimension (at least 5 cm vs less than 5 cm). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive radiotherapy once daily, 5 days a week, for 5.5 weeks, beginning on day 1. Patients also receive paclitaxel IV over 1 hour and gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Arm II: Patients receive chemoradiotherapy as in arm I. Within 3-8 weeks after completion of chemoradiotherapy, patients without disease progression receive oral tipifarnib twice daily for 21 days. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Official Title
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A Randomized Phase II Trial of Weekly Gemcitabine, Paclitaxel and External Irradiation (50.4 GY) Followed by the Farnesyl Transferase Inhibitor R115777 (NSC #702818) for Locally Advanced Pancreatic Cancer

Conditions
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Adenocarcinoma of the Pancreas, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: paclitaxel
* Drug: tipifarnib
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed unresectable, locally advanced adenocarcinoma of the pancreas Residual disease after resection (R1 or R2, microscopic or macroscopic) allowed No metastases in major viscera No peritoneal seeding or ascites Biliary or gastroduodenal obstruction must have drainage before starting study therapy Radiographically assessable disease encompassable within a single irradiation field (15 by 15 cm maximum) Performance status - Zubrod 0-1 Granulocyte count at least 1,800/mm^3 Platelet count at least 100,000/mm^3 ALT less than 3 times upper limit of normal Bilirubin less than 2.0 mg/dL Creatinine less than 3.0 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 2 years except non-melanoma skin cancer or carcinoma in situ of the cervix, uterus, or bladder No significant infection or other medical condition that would preclude study No prior chemotherapy (including gemcitabine or paclitaxel) for pancreatic cancer No other concurrent cytotoxic agents See Disease Characteristics No prior radiotherapy to the planned field No other concurrent radiotherapy See Disease Characteristics No other concurrent investigational agents
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (radiation therapy, paclitaxel, gemcitabine)<br>Patients receive radiotherapy once daily, 5 days a week, for 5.5 weeks, beginning on day 1. Patients also receive paclitaxel IV over 1 hour and gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. | Drug: gemcitabine hydrochloride<br>* Given IV<br>* Other names: Gemzar;Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Radiation: radiation therapy<br>* Undergo radiation therapy<br>* Other names: therapy, radiation;|
| Experimental: Arm II (radiation therapy, tipifarnib)<br>Patients receive chemoradiotherapy as in arm I. Within 3-8 weeks after completion of chemoradiotherapy, patients without disease progression receive oral tipifarnib twice daily for 21 days. | Drug: tipifarnib<br>* Given orally<br>* Other names: Zarnestra;Radiation: radiation therapy<br>* Undergo radiation therapy<br>* Other names: therapy, radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Calculated along with associated 95% confidence intervals. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of patients developing unacceptable toxicity defined as grade 3 or higher gastrointestinal or pulmonary toxicity and/or discontinuation of treatment | Graded according to the CTCAE version 3.0. | Up to 5 years | 
| Difference in overall survival between treatment regimens | Estimated with a 95% confidence interval. | 1 year | 
| Progression-free survival | Calculated along with associated 95% confidence intervals. | 1 year |