Tipifarnib and Gemcitabine in Treating Women With Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00100750
First received: January 6, 2005
Last updated: March 26, 2014
Last verified: December 2013

January 6, 2005
March 26, 2014
September 2005
December 2014   (final data collection date for primary outcome measure)
Objective response rate measured [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00100750 on ClinicalTrials.gov Archive Site
Time to disease progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Tipifarnib and Gemcitabine in Treating Women With Metastatic Breast Cancer
Gemcitabine and R115777 Combination Therapy for Metastatic Breast Cancer

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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Drug: gemcitabine hydrochloride
    Given IV
    Other Names:
    • dFdC
    • difluorodeoxycytidine hydrochloride
    • gemcitabine
    • Gemzar
  • Drug: tipifarnib
    Given orally
    Other Names:
    • R115777
    • Zarnestra
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.

Interventions:
  • Drug: gemcitabine hydrochloride
  • Drug: tipifarnib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
45
Not Provided
December 2014   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00100750
NCI-2009-00114, NCI-2009-00114, CDR0000409695, 2003-0992, 2003-0992, 7004, P30CA016672, N01CM62202
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Banu Arun M.D. Anderson Cancer Center
National Cancer Institute (NCI)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP