Clinical trial NCT00033514: Trastuzumab and Erlotinib as First-Line Therapy in Treating Women With Metastatic Breast Cancer Associated With HER2/Neu Overexpression
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: Jonsson Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2003-01-27
Enrollment: 27
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: 5 years
measure: Recommended Dose for Phase II
timeFrame: treatment period
Secondary outcomes:
measure: Duration of Objective Response
timeFrame: 5 years
measure: Incidence of Adverse Events
timeFrame: 5 years
measure: Serum Concentration of Herceptin at Specified Time-points.
timeFrame: 4 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Carolyn Britten, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.