Tipifarnib and Combination Chemotherapy in Treating Patients With Stage II or Stage III Breast Cancer - Full Text View

Sponsors and Collaborators:	New York Cancer Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00470301

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Breast Cancer	Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel Drug: pegfilgrastim Drug: tipifarnib Procedure: axillary lymph node dissection Procedure: conventional surgery	Phase I Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Paclitaxel Pegfilgrastim Tipifarnib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

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

Primary Outcome Measures:

Recommended phase II dose of tipifarnib when combined with weekly sequential paclitaxel (phase I) [ Designated as safety issue: Yes ]
Pathologic complete response rate (pCR) (phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical complete and partial response by RECIST criteria (phase II) [ Designated as safety issue: No ]
pCR rate in the breast and axillary lymph nodes (phase II) [ Designated as safety issue: No ]
Feasibility and safety (phase I and II) [ Designated as safety issue: Yes ]

Estimated Enrollment:	97
Study Start Date:	April 2007
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the recommended phase II dose of tipifarnib when given together with paclitaxel in patients with stage IIB-IIIC breast cancer. (Phase I)
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)
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.

PROJECTED ACCRUAL: A total of 97 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Female or male
Menopausal status not specified
ECOG performance status 0-1
WBC ≥ 3,000/mm³
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
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
FEV_1 ≥ 1 L*
DLCO ≥ 50%*
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
- Psychiatric illness/social situations that would preclude study compliance
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception NOTE: *Only if baseline CT scan of chest shows parenchymal lung disease OR there is a history of chronic obstructive or other pulmonary disease

PRIOR CONCURRENT THERAPY:

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)
No prior chemotherapy, radiotherapy, or definitive therapeutic surgery (e.g., mastectomy, lumpectomy, or axillary dissection) for this cancer
- 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00470301

Locations

United States, Georgia
MBCCOP - Medical College of Georgia Cancer Center	Recruiting
Augusta, Georgia, United States, 30912
Contact: Thomas A. Samuel 706-721-6878
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine	Recruiting
Bronx, New York, United States, 10461
Contact: Clinical Trials Office - Albert Einstein Cancer Center at Albe 718-904-2730 aecc@aecom.yu.edu
Beth Israel Medical Center - Petrie Division	Recruiting
New York, New York, United States, 10003-3803
Contact: Clinical Trials Office - Beth Israel Medical Center - Petrie D 212-844-6286
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Clinical Trials Office - Herbert Irving Comprehensive Cancer C 212-305-8615

Sponsors and Collaborators

New York Cancer Consortium

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Dawn Hershman, MD	Herbert Irving Comprehensive Cancer Center
Principal Investigator:	Joseph A. Sparano, MD	Albert Einstein College of Medicine of Yeshiva University

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000543434, NYCC-06-12-487
Study First Received:	May 3, 2007
Last Updated:	January 9, 2009
ClinicalTrials.gov Identifier:	NCT00470301
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Study placed in the following topic categories:

Skin Diseases
Paclitaxel
Breast Neoplasms
Cyclophosphamide

Doxorubicin
Breast Diseases
Tipifarnib

Additional relevant MeSH terms:

Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Antimitotic Agents
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009