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

NCT00068757 | Completed Phase 1

• 2 other identifiers: EORTC-16023-10051SPRI-P01900
• Study Type: interventional
• Target: 23
• Locations: 3 countries
• Sites: 3

Brief 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.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; male breast cancer; HER2-positive breast cancer

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity and maximum tolerated dose as measured by CTC v 2.0

Secondary Outcomes (3)

• Translational research

• Pharmacokinetics (PK) and pharmacodynamics (PD)

• Clinical response as measured by RECIST criteria

Interventions

trastuzumab BIOLOGICAL

lonafarnib DRUG

paclitaxel DRUG

pharmacological study OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (3)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Institut Curie Hopital

Paris, 75248, France

Location

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital

Amsterdam, 1066 CX, Netherlands

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Trastuzumab; lonafarnib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jan H. M. Schellens, MD, PhD

  The Netherlands Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2003
• First Posted: September 11, 2003
• Study Start: August 1, 2003
• Primary Completion: November 1, 2007
• Last Updated: September 12, 2012

Record last verified: 2012-09

Locations

BE (1); FR (1); NL (1)