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

Primary Purpose

Breast Cancer, Male Breast Cancer, Stage II Breast Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
tipifarnib
paclitaxel
doxorubicin
cyclophosphamide
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute
  • Albert Einstein College of Medicine
  • Montefiore Medical Center
  • Mount Sinai Medical Center
  • Columbia University Medical Center
  • Weill Medical College of Cornell University
  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

Tipifarnib plus sequential weekly paclitaxel followed by doxorubicin plus cyclophosphamide

Outcomes

Primary Outcome Measures

Pathologic Complete Response Rate (pCR)
An increase in the breast pCR from 15% (anticipated for chemotherapy alone) to 35% would be considered promising.
Number of Participants Analyzed for Phase II Dose of Tipifarnib When Combined With Weekly Sequential Paclitaxel (Phase I)
The recommended phase II dose of tipifarnib (100 or 200 mg PO BID on days 1-3 each paclitaxel dose) in combination with paclitaxel (80 mg/m2/week x 12 consecutive weeks)

Secondary Outcome Measures

Full Information

First Posted
May 3, 2007
Last Updated
January 29, 2021
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00470301
Brief Title
Tipifarnib and Combination Chemotherapy in Treating Patients With Stage II or Stage III Breast Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Male Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Tipifarnib plus sequential weekly paclitaxel followed by doxorubicin plus cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
tipifarnib
Other Intervention Name(s)
R115777, Zarnestra
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, TAX, Taxol
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Other Intervention Name(s)
ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Pathologic Complete Response Rate (pCR)
Description
An increase in the breast pCR from 15% (anticipated for chemotherapy alone) to 35% would be considered promising.
Time Frame
Up to 5 years
Title
Number of Participants Analyzed for Phase II Dose of Tipifarnib When Combined With Weekly Sequential Paclitaxel (Phase I)
Description
The recommended phase II dose of tipifarnib (100 or 200 mg PO BID on days 1-3 each paclitaxel dose) in combination with paclitaxel (80 mg/m2/week x 12 consecutive weeks)
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dawn Hershman
Organizational Affiliation
Montefiore Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Albert Einstein College of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467-2490
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24068539
Citation
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.
Results Reference
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Tipifarnib and Combination Chemotherapy in Treating Patients With Stage II or Stage III Breast Cancer

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