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

Breast Cancer Clinical Trial

Official title:

Phase I/II Study Of Herceptin Combined With OSI-774 In The First-Line Treatment Of Metastatic Breast Cancer Associated With HER2/Neu Overexpression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00033514
• Other study ID #: 01-06-020
• Secondary ID: CDR0000069295GEN
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2001
• Est. completion date: December 2011

Study information

• Verified date: February 2016
• Source: Jonsson Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab
Day 1 4mg/kg IV 2 mg/kg IV weekly.

Drug:
• 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.

Locations

Country	Name	City	State
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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: 10.3 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	5 years
Primary	Recommended Dose for Phase II		treatment period
Secondary	Duration of Objective Response		5 years
Secondary	Incidence of Adverse Events		5 years
Secondary	Serum Concentration of Herceptin at Specified Time-points.		4 months