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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00026104
First received: November 9, 2001
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Adenocarcinoma of the Pancreas
Stage II Pancreatic Cancer
Stage III Pancreatic Cancer
Drug: gemcitabine hydrochloride
Drug: paclitaxel
Drug: tipifarnib
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Calculated along with associated 95% confidence intervals.


Secondary Outcome Measures:
  • Frequency of patients developing unacceptable toxicity defined as grade 3 or higher gastrointestinal or pulmonary toxicity and/or discontinuation of treatment [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Graded according to the CTCAE version 3.0.

  • Difference in overall survival between treatment regimens [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Estimated with a 95% confidence interval.

  • Progression-free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Calculated along with associated 95% confidence intervals.


Enrollment: 154
Study Start Date: November 2001
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00026104

Locations
United States, Pennsylvania
Radiation Therapy Oncology Group
Philadelphia, Pennsylvania, United States, 19103
Sponsors and Collaborators
Investigators
Principal Investigator: Tyvin Rich Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00026104     History of Changes
Other Study ID Numbers: NCI-2012-02423, RTOG-PA-0020, RTOG-DEV-1003, CDR0000068986, U10CA021661
Study First Received: November 9, 2001
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Tipifarnib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on October 19, 2014