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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


Phase 2
N/A
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Principal Investigator

Paula Silverman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000299534

NCT ID:

NCT00060177

Start Date:

January 2003

Completion Date:

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • Breast Neoplasms

Name

Location

Ireland Cancer CenterCleveland, Ohio  44106-5065