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.
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
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
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
- Histologically confirmed unresectable, locally advanced adenocarcinoma of the
- 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
- 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