Tipifarnib Plus Trastuzumab in Treating Patients With Metastatic Breast Cancer

Sponsor

The University of Texas Health Science Center at San Antonio (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00054470

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining tipifarnib with trastuzumab may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining tipifarnib with trastuzumab in treating patients who have metastatic breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: trastuzumab Drug: tipifarnib	Phase 2

Detailed Description

OBJECTIVES:

Determine the antitumor activity of tipifarnib and trastuzumab (Herceptin) in patients with metastatic breast cancer.
Determine the safety and tolerability of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral tipifarnib twice daily on days 1-21 and trastuzumab (Herceptin) IV over 30-90 minutes on day 1. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 18-40 patients will be accrued for this study within 9-20 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Evaluation Of The Efficacy And Safety Of R115777 (NSC702818) A Non-Peptidomimetic Farnesyl Transferase Inhibitor, And Trastuzumab In Patients With Advanced Breast Cancer

Study Start Date :

Dec 1, 2002

Actual Primary Completion Date :

Jan 1, 2003

Actual Study Completion Date :

Jan 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed metastatic adenocarcinoma of the breast
HER2/neu 3+ by immunohistochemical staining
2+ eligible provided HER2/neu positive by fluorescent in-situ hybridization (FISH)
HER2/neu positive by FISH alone allowed
Unidimensionally measurable disease
At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
Must have received prior trastuzumab (Herceptin)
Patients with known brain metastases meeting any of the following criteria are not eligible:
Require high-dose steroid therapy or enzyme-inducing anticonvulsant drugs
No prior cranial radiotherapy
Have progressive neurologic dysfunction that would preclude study evaluation
Have evidence of progressive CNS disease by CT scan or MRI
Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS:

Age

Over 18

Sex

Male or female

Menopausal status

Not specified

Performance status

ECOG 0-2 OR
Karnofsky 70-100%

Life expectancy

At least 12 weeks

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 9.0 g/dL

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
AST and ALT no greater than 2.5 times ULN (5 times ULN if liver metastases present)

Renal

Creatinine no greater than 1.5 times ULN OR
Creatinine clearance greater than 60 mL/min

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
Ejection fraction greater than 50% by MUGA or echocardiogram

Gastrointestinal

No gastrointestinal tract disease resulting in an inability to tolerate oral medication
No requirement for IV alimentation
No active peptic ulcer disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No significant traumatic injury within the past 21 days
No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
No ongoing or active infection
No prior allergic reaction attributed to compounds of similar chemical or biological composition to tipifarnib (e.g., quinolones) or trastuzumab
No psychiatric illness or social situation that would preclude study compliance
No other concurrent medical illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
No prior bone marrow transplantation with high-dose chemotherapy
No concurrent immunotherapy

Chemotherapy

See Biologic therapy
No more than 2 prior chemotherapy regimens for metastatic disease
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Prior combination chemotherapy allowed
No concurrent chemotherapy

Endocrine therapy

See Disease Characteristics
Prior hormonal therapy allowed
No concurrent hormonal therapy for cancer

Radiotherapy

See Disease Characteristics
More than 4 weeks since prior wide-field radiotherapy and recovered
No concurrent radiotherapy

Surgery

Prior modified radical mastectomy or lumpectomy with axillary node dissection allowed
Prior resection of metastatic lesions allowed
More than 21 days since prior major surgery
No prior surgery affecting absorption

Other

No prior tipifarnib
More than 6 weeks since initiation of bisphosphonate therapy (if bone lesions are the only site of measurable disease)
Bisphosphonate therapy may not be initiated during study
No other concurrent investigational agents
No other concurrent anticancer therapy
No concurrent antacids within 2 hours of study drug