Gemcitabine and R115777 (Tipifarnib) Combination Therapy for Metastatic Breast Cancer
18 Years
N/A
Female
Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer
Trial Information
Gemcitabine and R115777 (Tipifarnib) Combination Therapy for Metastatic Breast Cancer
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Objective response rate measured
Outcome Time Frame:
Up to 5 years
Safety Issue:
No
Principal Investigator
Banu Arun
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00114
NCT ID:
NCT00100750
Start Date:
September 2005
Completion Date:
Related Keywords:
- Breast Cancer
- Recurrent Breast Cancer
- Stage IV Breast Cancer
- Breast Neoplasms
Name | Location |
|---|---|
| M D Anderson Cancer Center | Houston, Texas 77030 |
