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

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

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


- 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

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.

Inclusion Criteria


- 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



- 18 and over


- Female

Menopausal status

- Not specified

Performance status

- Zubrod 0-1

Life expectancy

- See Disease Characteristics


- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3


- 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


- Creatinine no greater than 1.5 mg/dL


- 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


Biologic therapy

- Not specified


- 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)


- No concurrent radiotherapy


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


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

JoAnne Zujewski, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

December 2002

Completion Date:

July 2006

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms



Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182
NCI - Center for Cancer Research Bethesda, Maryland  20892