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

Phase 1

Completed

• Conditions: Breast Cancer
• Interventions: Biological: trastuzumab; Drug: erlotinib hydrochloride

• Registration Number: NCT00033514
• Lead Sponsor: Jonsson Comprehensive Cancer Center

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.

Study Timeline

• Study Start: 2001-08
• Study First Submitted: 2002-04-09
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Status Verified: 2016-02
• Results First Submitted: 2016-02-11
• Results First Submitted QC: 2016-03-11
• Results First Posted: 2016-04-11
• Last Update Submitted: 2020-09-17
• Last Update Posted: 2020-10-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 27

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

Read More

Exclusion Criteria

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment	erlotinib hydrochloride	please see intervention description
treatment	trastuzumab	please see intervention description

Primary Outcome Measures

Name	Time	Method
The Objective Response Rate as Defined as Stable Disease or the Rate of Complete and Partial Responses Determined on Two Consecutive Occasions Greater Than or Equal to 4 Weeks Apart.	5 years	Complete Response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.; Partial Response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.
Recommended Dose for Phase II	treatment period

Secondary Outcome Measures

Name	Time	Method
Serum Concentration of Herceptin at Specified Time-points.	4 months
Duration of Objective Response	5 years
Incidence of Adverse Events	5 years

Trial Locations

Locations (1)

Jonsson Comprehensive Cancer Center at UCLA; 🇺🇸 Los Angeles, California, United States