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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00026104
Collaborator
NRG Oncology (Other)
154
1
2

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OBJECTIVES:
  1. Compare the 1-year survival rate in patients with locally advanced pancreatic cancer treated with paclitaxel, gemcitabine, and radiotherapy with or without tipifarnib.

  2. Determine the toxicity and loco-regional activity of this chemoradiotherapy regimen in these patients.

  3. Determine the feasibility and toxicity of prolonged administration of tipifarnib after chemoradiotherapy in these patients.

  4. 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 Design

Study Type:
Interventional
Actual Enrollment :
154 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Nov 1, 2001
Actual Primary Completion Date :
Aug 1, 2006

Arms and Interventions

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:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
  • Drug: paclitaxel
    Given IV
    Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
  • 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
  • Outcome Measures

    Primary Outcome Measures

    1. Overall survival [1 year]

      Calculated along with associated 95% confidence intervals.

    Secondary Outcome Measures

    1. Frequency of patients developing unacceptable toxicity defined as grade 3 or higher gastrointestinal or pulmonary toxicity and/or discontinuation of treatment [Up to 5 years]

      Graded according to the CTCAE version 3.0.

    2. Difference in overall survival between treatment regimens [1 year]

      Estimated with a 95% confidence interval.

    3. Progression-free survival [1 year]

      Calculated along with associated 95% confidence intervals.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Radiation Therapy Oncology Group Philadelphia Pennsylvania United States 19103

    Sponsors and Collaborators

    • National Cancer Institute (NCI)
    • NRG Oncology

    Investigators

    • Principal Investigator: Tyvin Rich, Radiation Therapy Oncology Group

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00026104
    Other Study ID Numbers:
    • NCI-2012-02423
    • RTOG-PA-0020
    • CDR0000068986
    • U10CA021661
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Oct 30, 2020
    Last Verified:
    Oct 1, 2020
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 30, 2020