Lonafarnib, Trastuzumab, and Paclitaxel in Treating Patients With HER2/Neu-Overexpressing Stage IIIB, Stage IIIC, or Stage IV Breast Cancer

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Lonafarnib may stop the growth of tumor cells by blocking the enzymes necessary for their 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 lonafarnib and trastuzumab with paclitaxel may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lonafarnib when given together with trastuzumab and paclitaxel in treating patients with HER2/neu-overexpressing stage IIIB, stage IIIC, or stage IV breast cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Treatments: Albumin-Bound Paclitaxel; Lonafarnib; Paclitaxel; Trastuzumab

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer

• Stage IIIB, IIIC, or IV

• HER2/neu overexpression

• 3+ by immunohistochemistry

• 2+ allowed if positive fluorescent in situ hybridization

• Disease meets the following treatment criteria:

• Paclitaxel/trastuzumab (Herceptin®) may be appropriate therapy

• Anthracycline therapy is not a suitable approach

• No clinical signs of CNS involvement

• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2 OR

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Hemoglobin at least 10.0 g/dL (6.2 mmol/L)

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

• Alkaline phosphatase less than 2.5 times ULN (5 times ULN if liver metastases are present)

• AST and ALT less than 2.5 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine clearance at least 40 mL/min

Cardiovascular

• Cardiac ejection fraction normal by MUGA

• QTc interval no greater than 440 msec

• No cardiac dysfunction

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for up to 3 months after study participation

• No concurrent severe/unstable systemic disease

• No infection

• No circumstances that would preclude study participation (e.g., alcoholism or substance abuse)

• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 1 year since prior trastuzumab

• No concurrent prophylactic growth factors

Chemotherapy

• More than 1 year since prior paclitaxel

• More than 4 weeks since other prior chemotherapy

Endocrine therapy

• More than 1 day since prior hormonal therapy

• More than 2 days since prior high-dose chronic steroids

• More than 2 days since prior ethinyl estradiol

• No concurrent high-dose chronic steroids

• No concurrent ethinyl estradiol

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• Not specified

Other

• More than 2 days since prior administration of and no concurrent CYP3A4 inducers or inhibitors, including any of the following:

• Gestodene

• Itraconazole

• Ketoconazole

• Cimetidine

• Erythromycin

• Carbamazepine

• Phenobarbital

• Phenytoin

• Rifampin

• Sulfinpyrazone

• No concurrent grapefruit juice

• No other concurrent anticancer agents

• No other concurrent investigational therapy