Tipifarnib and Gemcitabine Hydrochloride in Treating Women With Metastatic Breast Cancer

January 12, 2015 updated by: National Cancer Institute (NCI)

Gemcitabine and R115777 Combination Therapy for Metastatic Breast Cancer

This phase I/II trial is studying the side effects and best dose of tipifarnib when given together with gemcitabine hydrochloride and to see how well they work in treating women with breast cancer that has spread to other parts of the body. Tipifarnib is a drug that binds to specific proteins on the tumor cells and then kills these cells. Gemcitabine hydrochloride is a chemotherapy drug that may kill tumor cells by preventing cells from dividing. Giving tipifarnib together with gemcitabine hydrochloride may kill more tumor cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the objective response rate of the combination of gemcitabine (gemcitabine hydrochloride) and the farnesyltransferase inhibitor tipifarnib (R115777) in patients with metastatic breast cancer.

II. To evaluate the duration of response, time to disease progression in patients with metastatic breast cancer treated with the combination of gemcitabine and tipifarnib (R115777).

OUTLINE: This is a phase I, dose-escalation study of tipifarnib followed by a phase II study.

Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-14 and gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologically confirmed breast cancer and clinical evidence of metastatic disease
  • Patients may have received any number or type of hormonal therapies, either for stage IV disease and/or as adjuvant therapy; patients may have received trastuzumab therapy
  • Patients may have received up to 2 prior chemotherapy regimens as therapy for metastatic breast cancer; patients must have recovered from the myelosuppressive effects of prior chemotherapy and all toxicity must have recovered to grade less than or equal to 1
  • Concomitant bisphosphonates are allowed for patients with bone metastases
  • Localized radiotherapy that does not influence the single evaluable lesion is allowed prior to the initiation of therapy; patients must have recovered from the myelosuppressive effects of previous radiotherapy (at least 4 weeks)
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky > 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • There should be a four-week delay between the conclusion of radiation and the start of gemcitabine, provided the acute effects of radiation treatment have resolved

Exclusion Criteria:

  • Prior therapy with farnesyltransferase inhibitor or gemcitabine for metastatic breast cancer
  • Patients with leptomeningeal disease and/or brain metastasis
  • Patients with symptomatic lymphangitic pulmonary metastases
  • Patients with peripheral neuropathy greater than or equal to grade 2
  • No history of concomitant malignancy except for non-melanoma skin cancer or cervical cancer in situ or other malignancy treated curatively and no evidence of disease for at least five years
  • Patients who have had chemotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777), or imidazole derivatives
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (gemcitabine hydrochloride, tipifarnib)
Patients receive tipifarnib PO BID on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • dFdC
Drug: Tipifarnib
Given PO
Other Names:
  • R115777
  • Zarnestra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Up to 9 years
Up to 9 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to disease progression using RECIST
Time Frame: Up to 9 years
Up to 9 years
Incidence of adverse events observed during treatment, graded using the Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 30 days after completion of study treatment
Up to 30 days after completion of study treatment
ORR, by type and extent of prior chemotherapy
Time Frame: Up to 9 years
Up to 9 years

Other Outcome Measures

Outcome Measure
Time Frame
Change in serum proteomic analysis
Time Frame: Baseline to up to 9 years
Baseline to up to 9 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

October 1, 2007

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

January 6, 2005

First Submitted That Met QC Criteria

January 6, 2005

First Posted (Estimate)

January 7, 2005

Study Record Updates

Last Update Posted (Estimate)

January 13, 2015

Last Update Submitted That Met QC Criteria

January 12, 2015

Last Verified

October 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00114 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA016672 (U.S. NIH Grant/Contract)
  • N01CM62202 (U.S. NIH Grant/Contract)
  • N01CM17003 (U.S. NIH Grant/Contract)
  • 7004 (CTEP)
  • CDR0000409695
  • 2003-0992 (Other Identifier: M D Anderson Cancer Center)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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