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Tipifarnib and Gemcitabine in Treating Women With Metastatic Breast Cancer

This study has suspended participant recruitment.
(CTEP trial, missing information)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00100750
First received: January 6, 2005
Last updated: January 2, 2013
Last verified: January 2013
History of Changes
  Purpose

This phase I/II trial is studying the side effects and best dose of tipifarnib when given together with gemcitabine and to see how well they work in treating women with metastatic breast cancer. Tipifarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with gemcitabine may kill more tumor cells


Condition Intervention Phase
Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
 Drug: gemcitabine hydrochloride
Drug: tipifarnib
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Gemcitabine and R115777 (Tipifarnib) Combination Therapy for Metastatic Breast Cancer

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Objective response rate measured [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to disease progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: September 2005
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

Phase I: Patients receive oral tipifarnib twice daily on days 1-14 and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive 1 of 2 doses of tipifarnib to determine a safe tolerable dose. A safe tolerable dose is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive tipifarnib as in phase I (at the dose established in phase I) and gemcitabine as in phase I.

 Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra

Detailed Description:

OBJECTIVES:

I. Determine the objective response rate in women with metastatic breast cancer treated with tipifarnib and gemcitabine.

II. Determine the duration of response and time to disease progression in patients treated with this regimen.

OUTLINE: This is a multicenter phase I, dose-finding study of tipifarnib, followed by a phase II study.

PHASE I: Patients receive oral tipifarnib twice daily on days 1-14 and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive 1 of 2 doses of tipifarnib to determine a safe tolerable dose. A safe tolerable dose is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive tipifarnib as in phase I (at the dose established in phase I) and gemcitabine as in phase I.

Patients are followed at 3 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • No more than 2 prior chemotherapy regimens for metastatic breast cancer
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • Concurrent bisphosphonates allowed for bone metastases

  • Histologically confirmed breast cancer:

    • Clinical evidence of metastatic disease

  • Measurable disease:

    • At least 1 unidimensionally measurable lesion > 20 mm by conventional techniques OR > 10 mm by spiral CT scan
  • No known brain metastases and/or leptomeningeal disease
  • No symptomatic lymphangitic pulmonary metastases

  • Hormone receptor status:

    • Not specified

  • Menopausal status:

    • Not specified

  • Performance status:

    • ECOG 0-2 OR Karnofsky 70-100%

  • Hematopoietic:

    • WBC >= 3,000/mm3
    • Absolute neutrophil count >= 1,500/mm3
    • Platelet count >= 100,000/mm3

  • Hepatic:

    • Bilirubin normal
    • AST or ALT =< 2.5 times upper limit of normal

  • Renal:

    • Creatinine normal OR creatinine clearance >= 60 mL/min

  • Cardiovascular:

    • No symptomatic congestive heart failure
    • No unstable angina pectoris
    • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to tipifarnib or imidazole derivatives (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
  • No peripheral neuropathy >= grade 2
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • Prior trastuzumab (Herceptin) allowed
  • No prior gemcitabine for metastatic breast cancer
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • Prior hormonal therapy for stage IV disease and/or as adjuvant therapy allowed
  • No prior localized radiotherapy to a single evaluable lesion
  • No prior farnesyltransferase inhibitors for metastatic breast cancer
  • No other uncontrolled illness
  • No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
  • More than 4 weeks since prior radiotherapy and recovered

Exclusion Criteria:

  • central nervous system metastases
  • congestive heart failure
  • performance status 3
  • performance status 4
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00100750

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Banu Arun M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00100750     History of Changes
Other Study ID Numbers: NCI-2009-00114, 2003-0992, N01CM17003, N01CM62202
Study First Received: January 6, 2005
Last Updated: January 2, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Tipifarnib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on June 18, 2013