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
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
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
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