Tipifarnib Plus Tamoxifen in Treating Women With Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00052728
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 19, 2013
Information provided by:
National Cancer Institute (NCI)

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:


  • 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 Type : Interventional  (Clinical Trial)
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 : December 2002
Actual Study Completion Date : July 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • 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 tumor)


  • 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 progression


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00052728

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Study Chair: JoAnne Zujewski, MD National Cancer Institute (NCI)

Publications of Results:
Lebowitz PF, Eng-Wong J, Balis F, et al.: A phase I trial of tipifarnib, a farnesyltransferase inhibitor, and tamoxifen in hormone-receptor positive metastatic breast cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 22 (Suppl 14): A-644, 38s, 2004. Identifier: NCT00052728     History of Changes
Obsolete Identifiers: NCT00048867
Other Study ID Numbers: CDR0000258720
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: June 19, 2013
Last Verified: May 2005

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents