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
Inclusion Criteria
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
