This trial is active, not recruiting.

Conditions breast cancer, male breast cancer, stage ii breast cancer, stage iiia breast cancer, stage iiib breast cancer, stage iiic breast cancer
Treatments tipifarnib, paclitaxel, doxorubicin hydrochloride, cyclophosphamide, pegfilgrastim, conventional surgery, axillary lymph node dissection
Phase phase 1/phase 2
Sponsor National Cancer Institute (NCI)
Start date April 2007
End date April 2012
Trial size 60 participants
Trial identifier NCT00470301, 06-12-487, 7868, CDR0000543434, N01CM62202, N01CM62204, NCI-2009-00239, P30CA013330


Tipifarnib may stop the growth of breast cancer by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with combination chemotherapy may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of tipifarnib when given together with combination chemotherapy and to see how well they work in treating patients with stage II or stage III breast cancer.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
See Detailed Description
tipifarnib R115777
Given orally
paclitaxel Anzatax
Given IV
doxorubicin hydrochloride ADM
Given IV
cyclophosphamide CPM
Given IV
pegfilgrastim Filgrastim SD-01
Given SC
conventional surgery surgery, conventional
surgical procedures performed on patients
axillary lymph node dissection
correlative study

Primary Outcomes

Recommended phase II dose of tipifarnib when combined with weekly sequential paclitaxel (phase I)
time frame: 2 weeks
Pathologic complete response rate (pCR) evaluated using RECIST (phase II)
time frame: Up to 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Bilirubin normal - AST and ALT =< 2.5 times upper limit of normal - LVEF normal by echocardiogram or nuclear scan - Creatinine normal OR Creatinine clearance >= 60 mL/min - No other invasive malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix - No history of allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib or other study drugs (e.g., imidazoles or quinolones) - No other uncontrolled illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would preclude study compliance - Not pregnant or nursing - Negative pregnancy test - At least 1 week since prior tamoxifen or other selective estrogen receptor modulator for prevention or for other indications (e.g., osteoporosis or prior ductal carcinoma in situ) - FEV1 >= 1 L* and DLCO >= 50%* [Note: *Only if baseline CT scan of chest shows parenchymal lung disease OR there is a history of chronic obstructive or other pulmonary disease] - No prior chemotherapy, radiotherapy, or definitive therapeutic surgery (e.g., mastectomy, lumpectomy, or axillary dissection) for this cancer but prior sentinel lymph node biopsy for this malignancy allowed - No prior adjuvant chemotherapy for a previous breast malignancy - No concurrent combination antiretroviral therapy for HIV-positive patients - No other concurrent investigational agents - No other concurrent anticancer agents or therapies - Histologically or cytologically confirmed adenocarcinoma of the breast; clinical stage IIB, IIIA, IIIB, or IIIC disease - HER-2/neu-negative by DAKO Herceptest or fluorescence in situ hybridization (FISH) - The following prior or concurrent diagnoses are allowed: - Lobular carcinoma in situ - Contralateral ductal carcinoma in situ - Contralateral invasive ductal and/or lobular cancer - Hormone receptor status: - Estrogen and/or progesterone receptor-positive* [Note: *Patients enrolled on the phase I portion of the trial may have estrogen and progesterone receptor-negative disease] - WBC >= 3,000/mm^3 - Absolute neutrophil count >= 1,500/mm^3 - Platelet count >= 100,000/mm^3 - ECOG performance status 0-1 - Fertile patients must use effective contraception

Additional Information

Official title A Phase I-II Study of R115777 (Tipifarnib, Zarnestra®) Plus Sequential Weekly Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide in Patients With Stage IIB-IIIC Breast Cancer
Principal investigator Dawn Hershman
Description PRIMARY OBJECTIVES: I. To determine the recommended phase II dose of tipifarnib when given together with paclitaxel in patients with stage IIB-IIIC breast cancer. (Phase I) II. To determine the pathologic complete remission rate (including breast and breast plus axillary nodes) in patients treated with sequential paclitaxel and tipifarnib followed by dose-dense doxorubicin hydrochloride, cyclophosphamide, and tipifarnib. (Phase II) III. To determine the feasibility and safety of this regimen in these patients. (Phase I and II) OUTLINE: This is a multicenter, phase I, dose-escalation study of tipifarnib followed by a phase II study. PHASE I: Paclitaxel plus tipifarnib: Patients receive paclitaxel IV over 1 hour on day 1 and oral tipifarnib twice daily on days 1-3. Treatment repeats weekly for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with no evidence of disease progression after 12 courses proceed to AC chemotherapy plus tipifarnib. Cohorts of 3-6 patients receive escalating doses of tipifarnib until the recommended phase II dose (RTPD) is determined. The RTPD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. AC chemotherapy plus tipifarnib: Patients receive doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes on day 1, oral tipifarnib twice daily on days 2-7, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. PHASE II: Patients receive paclitaxel and tipifarnib at the RTPD and AC chemotherapy plus tipifarnib as in phase I. After completion of AC plus tipifarnib (in both phases), patients are re-evaluated for surgery (i.e., modified radical mastectomy, radical mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection). After completion of study treatment, patients are followed every 6 months for 5 years and then annually for 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in February 2014.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).