Tipifarnib and Gemcitabine Hydrochloride in Treating Women With Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00100750
First received: January 6, 2005
Last updated: July 18, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Breast Cancer
Stage IV Breast Cancer
Drug: gemcitabine hydrochloride
Drug: tipifarnib
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Gemcitabine and R115777 Combination Therapy for Metastatic Breast Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: Up to 9 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to disease progression [ Time Frame: Up to 9 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • ORR, by type and extent of prior chemotherapy [ Time Frame: Up to 9 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change in serum proteomic analysis [ Time Frame: Baseline to up to 9 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: September 2005
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: tipifarnib
Given PO
Other Names:
  • R115777
  • Zarnestra
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00100750

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Banu Arun M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00100750     History of Changes
Other Study ID Numbers: NCI-2009-00114, NCI-2009-00114, CDR0000409695, 2003-0992, 2003-0992, 7004, N01CM62202, P30CA016672, N01CM17003
Study First Received: January 6, 2005
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Tipifarnib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 20, 2014