Tipifarnib Plus Tamoxifen in Treating Women With Metastatic Breast Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00052728

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Tamoxifen may fight breast cancer by blocking the use of estrogen. Combining tipifarnib with tamoxifen may be effective treatment for metastatic breast cancer.

PURPOSE: This phase II trial is studying how well giving tipifarnib together with tamoxifen works in treating women with metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: tamoxifen citrate Drug: tipifarnib	Phase 2

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose and recommended phase II dose of tipifarnib administered with tamoxifen in women with hormone receptor-positive metastatic breast cancer (Phase I closed to accrual effective 10/23/2003).
Determine the acute and chronic toxicity of this regimen in these patients.
Determine the pharmacokinetics of this regimen in these patients.
Determine the response rate and time to progression in patients treated with this regimen.

OUTLINE: This is an open-label study of tipifarnib (Phase I closed to accrual effective 10/23/2003). Patients are stratified according to benefit from prior hormonal therapy (yes vs no) (phase II).

Phase I (closed to accrual effective 10/23/2003): Patients receive oral tipifarnib twice daily on days 1-21. Patients also receive oral tamoxifen daily on days 8-18 (during course I only) and on days 1-28 during all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Once the MTD is determined, additional patients are accrued and treated at that dose level in the phase II portion of the study.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 9-12 patients will be accrued for the phase I portion of this study (Phase I closed to accrual effective 10/23/2003). A total of 27-40 patients will be accrued for the phase II portion of this study within 3 years.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial Of Tipifarnib (R15777, ZARNESTRA) In Combination With Tamoxifen In Subjects With Metastatic Breast Cancer

Study Start Date :

Dec 1, 2002

Actual Study Completion Date :

Jul 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of metastatic (stage IV) breast cancer
Evidence of disease progression
Measurable disease
Must have been previously treated with at least 1 hormonal therapy with either an aromatase inhibitor or an estrogen receptor (ER)-modulating drug in the adjuvant or metastatic setting and meets 1 of the following criteria:
Hormone-responsive disease:
Stable disease (no recurrence or progression for at least 6 months)
Objective response
Hormone-nonresponsive disease:
No stable disease
No objective response
Previously treated CNS disease allowed provided patient has a life expectancy of at least 3 months (phase I patients) (Phase I closed to accrual effective 10/23/2003)
No CNS metastases (phase II patients)
Hormone receptor status:
ER and/or progesterone receptor positive
NOTE: As few as 1% positive cells considered positive

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Female

Menopausal status

Not specified

Performance status

Zubrod 0-1

Life expectancy

See Disease Characteristics

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 2.0 mg/dL (unless evidence of Gilbert's disease)
SGOT and SGPT less than 3 times upper limit of normal (unless liver involvement by tumor)

Renal

Creatinine no greater than 1.5 mg/dL

Other

Not pregnant
Negative pregnancy test
Fertile patients must use effective nonhormonal contraception during and for 2 months after study participation
No medical or psychiatric condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No more than 2 prior chemotherapy regimens for metastatic disease (phase II patients)
No limitations on prior neoadjuvant or adjuvant regimens
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

See Disease Characteristics
At least 6 months since prior tamoxifen
Concurrent stable dose of steroids allowed (phase I patients) (Phase I closed to accrual effective 10/23/2003)

Radiotherapy

No concurrent radiotherapy

Surgery

Concurrent surgery allowed provided the need for surgery is not due to disease progression

Other

Recovered from all prior therapy
No prior warfarin
No concurrent cytochrome p450-inducing anti-convulsants
No other concurrent anticancer therapies
Concurrent bisphosphonates for bone metastases allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
2	NCI - Center for Cancer Research	Bethesda	Maryland	United States	20892