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

NCT ID: NCT00033514

Last Updated: 2020-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-08-31
• Study Completion Date: 2011-12-31

Brief Summary

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.

Detailed 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment

please see intervention description

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: BIOLOGICAL

Day 1 4mg/kg IV 2 mg/kg IV weekly.

erlotinib hydrochloride

Intervention Type: DRUG

100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.

Interventions

trastuzumab

Day 1 4mg/kg IV 2 mg/kg IV weekly.

Intervention Type: BIOLOGICAL

erlotinib hydrochloride

100 mg daily on Course 1 Day 2. After three weeks patients who have not experienced specific adverse events, dose will be escalated to 150 mg daily. Patients who have experienced specific adverse events dose will remain 100 mg daily or dose reduced as necessary per protocol.

Intervention Type: DRUG

Other Intervention Names

Herceptin; OSI-774

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carolyn Britten, MD

Role: PRINCIPAL_INVESTIGATOR

Jonsson Comprehensive Cancer Center

Locations

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Countries

United States

References

Britten CD, Finn RS, Bosserman LD, Wong SG, Press MF, Malik M, Lum BL, Slamon DJ. A phase I/II trial of trastuzumab plus erlotinib in metastatic HER2-positive breast cancer: a dual ErbB targeted approach. Clin Breast Cancer. 2009 Feb;9(1):16-22. doi: 10.3816/CBC.2009.n.003.

Reference Type: RESULT

PMID: 19299235 (View on PubMed)

Other Identifiers

CDR0000069295

Identifier Type: -

Identifier Source: secondary_id

GENENTECH-OSI2365s

Identifier Type: -

Identifier Source: secondary_id

NCI-G02-2057

Identifier Type: -

Identifier Source: secondary_id

01-06-020

Identifier Type: -

Identifier Source: org_study_id