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Letrozole With or Without Tipifarnib in Treating Women With Locally Advanced, Locally Recurrent, or Metastatic Breast Cancer
The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2004 by National Cancer Institute (NCI).   Recruitment status was  Active, not recruiting

First Received on May 6, 2003.   Last Updated on February 12, 2011   History of Changes
Sponsor: University Hospitals Seidman Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00060177
  Purpose

RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. Combining tipifarnib with letrozole may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of letrozole with or without tipifarnib in treating women with locally advanced, locally recurrent, or metastatic breast cancer that has progressed after antiestrogen therapy.


Condition Intervention Phase
Breast Cancer
Drug: letrozole
Drug: tipifarnib
Phase II

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Blinded, Phase 2 Study of Letrozole Plus the Farnesyl Transferase Inhibitor ZARNESTRA (R115777) and Letrozole Plus Placebo in the Treatment of Advanced Breast Cancer After Antiestrogen Therapy

Resource links provided by NLM:


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

Study Start Date: January 2003
Detailed Description:

OBJECTIVES:

  • Compare the efficacy of letrozole with or without tipifarnib based on an objective response rate in women with locally advanced, locoregionally recurrent, or metastatic breast cancer that has progressed after antiestrogen therapy.
  • Compare the time to progression, time to treatment failure, and survival in patients treated with these regimens.
  • Compare the clinical benefit rate in patients treated with these regimens.
  • Compare the duration of response and duration of clinical benefit in patients treated with these regimens.
  • Compare the safety and tolerability of these regimens in these patients.
  • Determine the pharmacokinetics of tipifarnib in these patients.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral letrozole once daily and oral placebo twice daily on days 1-21.
  • Arm II: Patients receive oral letrozole once daily and oral tipifarnib twice daily on days 1-21.

Courses in both arms repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30-42 days and every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 120 patients (40 for arm I and 80 for arm II) will be accrued for this study.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed breast cancer in 1 of the following disease states:

    • Locally advanced
    • Locoregionally recurrent
    • Metastatic
  • Documented disease progression on or after antiestrogen therapy, given in 1 of the following ways:

    • As adjuvant therapy (for at least 12 months)
    • As first-line therapy for advanced disease, on which the patient had an objective response (partial or complete) or stable disease for at least 6 months
  • Measurable disease

    • If the sole indicator lesion is in a previously irradiated area, recurrence of the lesion must be biopsy proven
  • No rapidly progressive, life-threatening metastases, including:

    • CNS metastases
    • Diffuse lymphangitis carcinomatosa of the lung
    • Metastases occupying more than 1/3 of the liver
  • Hormone receptor status:

    • Estrogen receptor- or progesterone receptor-positive (i.e., primary or secondary tumor tissue positive by any assay)

PATIENT CHARACTERISTICS:

Age

  • See Menopausal status

Sex

  • Female

Menopausal status

  • Postmenopausal, defined as any of the following:

    • Over 50 years of age and no menstruation for more than 12 months
    • Any age with castrate levels of follicle-stimulating hormone
    • Underwent prior bilateral oopherectomy

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count normal
  • Platelet count normal

Hepatic

  • Bilirubin no greater than 2 mg/dL
  • AST and ALT no greater than 2.5 times upper limit of normal (ULN)

Renal

  • Creatinine no greater than 1.5 times ULN

Other

  • No other malignancy within the past 5 years except contralateral breast carcinoma, basal cell or nonmetastatic squamous cell skin cancer, carcinoma in situ of the cervix, or stage I carcinoma of the cervix
  • No symptomatic peripheral neuropathy
  • No known or suspected allergy to letrozole or imidazole drugs (e.g., clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, or terconazole)
  • No coexisting medical condition that would interfere with study procedures and/or results

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No more than 1 prior chemotherapy regimen, given as adjuvant therapy or for metastatic disease (not both)

Endocrine therapy

  • See Disease Characteristics
  • No prior systemic endocrine therapy (including aromatase inhibitors) except antiestrogen therapy (e.g., tamoxifen)

Radiotherapy

  • See Disease Characteristics

Surgery

  • Not specified

Other

  • At least 30 days since prior participation in another investigational study
  • No prior farnesyl transferase inhibitor therapy
  • No other concurrent anticancer treatment
  • Concurrent bisphosphonates allowed for bone metastases present at baseline
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00060177

Locations
United States, Ohio
Ireland Cancer Center
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
University Hospitals Seidman Cancer Center
Investigators
Study Chair: Paula Silverman, MD Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00060177     History of Changes
Other Study ID Numbers: CDR0000299534, CWRU-JJPR-1102, JJPRD-R115777-INT-22
Study First Received: May 6, 2003
Last Updated: February 12, 2011
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Tipifarnib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012