Official Title: “A Phase II Trial Of Tipifarnib (R15777, ZARNESTRA) In Combination With Tamoxifen In Subjects With Metastatic Breast Cancer”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

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.

Intervention(s) in this Clinical Trial

• Drug: tamoxifen citrate
• Drug: tipifarnib

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: NCI - Center for Cancer Research-Medical Oncology

Overall Clinical Trial Officials and Contacts

JoAnne Zujewski, MD Study Chair NCI - Center for Cancer Research-Medical Oncology  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00052728

Study ID Number: CDR0000258720

ClinicalTrials.gov Identifier: NCT00052728

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database