Tipifarnib and Combination Chemotherapy in Treating Patients With Stage II or Stage III Breast Cancer

NCT ID: NCT00470301

Last Updated: 2021-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2013-09-30

Brief Summary

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.

Detailed 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.

Conditions

Breast Cancer; Male Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Tipifarnib plus sequential weekly paclitaxel followed by doxorubicin plus cyclophosphamide

Group Type: EXPERIMENTAL

tipifarnib

Intervention Type: DRUG

Given orally

paclitaxel

Intervention Type: DRUG

Given IV

doxorubicin

Intervention Type: DRUG

Given IV

cyclophosphamide

Intervention Type: DRUG

Given IV

Interventions

tipifarnib

Given orally

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

doxorubicin

Given IV

Intervention Type: DRUG

cyclophosphamide

Given IV

Intervention Type: DRUG

Other Intervention Names

R115777; Zarnestra; Anzatax; Asotax; TAX; Taxol; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF; CPM; CTX; Cytoxan; Endoxan; Endoxana

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast; clinical stage IIB, IIIA, IIIB, or IIIC disease
• 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)
• HER-2/neu-negative by immunohistochemistry or fluorescence in situ hybridization (FISH)
• 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]
• Normal organ function including:
• WBC >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• 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
• 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
• ECOG performance status 0-1
• Fertile patients must use effective contraception

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dawn Hershman

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Weill Medical College of Cornell University

New York, New York, United States

Albert Einstein College of Medicine

The Bronx, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Andreopoulou E, Vigoda IS, Valero V, Hershman DL, Raptis G, Vahdat LT, Han HS, Wright JJ, Pellegrino CM, Cristofanilli M, Alvarez RH, Fehn K, Fineberg S, Sparano JA. Phase I-II study of the farnesyl transferase inhibitor tipifarnib plus sequential weekly paclitaxel and doxorubicin-cyclophosphamide in HER2/neu-negative inflammatory carcinoma and non-inflammatory estrogen receptor-positive breast carcinoma. Breast Cancer Res Treat. 2013 Oct;141(3):429-35. doi: 10.1007/s10549-013-2704-x. Epub 2013 Sep 26.

Reference Type: RESULT

PMID: 24068539 (View on PubMed)

Other Identifiers

NCI-2009-00239

Identifier Type: OTHER

Identifier Source: secondary_id

06-12-487

Identifier Type: OTHER

Identifier Source: secondary_id

7868

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA013330

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62202

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62204

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00239

Identifier Type: -

Identifier Source: org_study_id