Trastuzumab and Erlotinib as First-Line Therapy in Treating Women With Metastatic Breast Cancer Associated With HER2/Neu Overexpression

Jonsson Comprehensive Cancer Center

Status and phase: Completed; Phase 2; Phase 1

Conditions: Breast Cancer

Treatments: Biological: trastuzumab; Drug: erlotinib hydrochloride

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00033514

01-06-020

CDR0000069295

NCI-G02-2057

GENENTECH-OSI2365s

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Biological therapies such as erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Combining trastuzumab with erlotinib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with erlotinib as first-line therapy in treating women who have metastatic breast cancer associated with HER2/neu overexpression.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of erlotinib when combined with trastuzumab (Herceptin) as first-line therapy in women with metastatic breast cancer associated with HER2/neu overexpression. (Phase I closed to accrual as of 01/2004)
• Determine the safety profile of this regimen in these patients.
• Determine the rate and duration of objective response in patients treated with this regimen.
• Determine the pharmacologic behavior of this regimen in these patients.
• Determine time to disease progression and duration of survival in patients treated with this regimen.
• Correlate the antitumor activity of this regimen with epidermal growth factor receptor expression in these patients.

OUTLINE: This is a dose-escalation study of erlotinib. (Phase I closed to accrual as of 01/2004).

Patients receive oral erlotinib once daily beginning on day 2 and trastuzumab (Herceptin) IV over 30-90 minutes (1-4 hours after erlotinib) once weekly beginning on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at the recommended phase II dose.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for the phase I portion (closed to accrual as of 01/2004) and 27-81 patients will be accrued for the phase II portion of this study.

Enrollment: 27 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women aged > 18 years
• Histologically documents metastatic breast cancer
• HER2 positive using Fluorescence In Situ Hybridization (FISH)
• For phase I, patients who have previously received treatment for their metastatic disease are allowed to participate.
• For the phase II portion of the study, patients must have measureable disease (> 2 cm; > 1 cm on spiral CT scan)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• A life expectancy of > 3 months
• Use of effective means of contraception

Exclusion criteria

• For Phase II, prior cytotoxic chemotherapy and/or prior Herceptin for their metastatic disease. Prior treatment in the adjuvant setting is allowed.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 1 patient group

treatment

Experimental group

Description:

please see intervention description

Treatment:

Drug: erlotinib hydrochloride

Biological: trastuzumab