Combination Chemotherapy Plus Radiation Therapy With or Without Tipifarnib in Treating Patients With 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.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma of the Pancreas; Stage III Pancreatic Cancer; Stage II Pancreatic Cancer
• Intervention / Treatment: Drug: tipifarnib; Drug: gemcitabine hydrochloride; Drug: paclitaxel; Radiation: radiation therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Radiation Therapy Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (radiation therapy, paclitaxel, gemcitabine); 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; Given IV; Other Names: Gemzar; gemcitabine; dFdC; difluorodeoxycytidine hydrochloride; Drug: paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; TAX; Radiation: radiation therapy; Undergo radiation therapy; Other Names: irradiation; radiotherapy; therapy, radiation
Experimental: Arm II (radiation therapy, tipifarnib); 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; Given orally; Other Names: R115777; Zarnestra; Radiation: radiation therapy; Undergo radiation therapy; Other Names: irradiation; radiotherapy; therapy, radiation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Tyvin Rich, Radiation Therapy Oncology Group

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Primary Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: November 9, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 29, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel; Tipifarnib
• Other Study ID Numbers: NCI-2012-02423; U10CA021661 (U.S. NIH Grant/Contract); RTOG-PA-0020; CDR0000068986