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Tipifarnib Plus Tamoxifen in Treating Women With Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00052728
First received: January 24, 2003
Last updated: June 18, 2013
Last verified: May 2005
  Purpose

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 Intervention Phase
Breast Cancer
Drug: tamoxifen citrate
Drug: tipifarnib
Phase 2

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: December 2002
Study Completion Date: July 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052728

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

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00052728     History of Changes
Obsolete Identifiers: NCT00048867
Other Study ID Numbers: CDR0000258720, NCI-03-C-0037, NCI-5540
Study First Received: January 24, 2003
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

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

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

ClinicalTrials.gov processed this record on November 19, 2014