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