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

This study has been completed.
National Cancer Institute (NCI)
Genentech, Inc.
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center Identifier:
First received: April 9, 2002
Last updated: October 29, 2015
Last verified: August 2013

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.

Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: erlotinib hydrochloride
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • The objective response rate as defined as the rate of complete and partial responses determined on two consecutive occasions greater than or equal to 4 weeks a part. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of objective response, time to disease progression, and duration of survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Incidence and severity of adverse events [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Serum concentration of Herceptin at specified time-points. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • Measurement of HER2 shedding in blood samples and the examination of skin biopsies for EGFR expression and phosphorylation, mitogen-activated protein kinase phosphorylation, and cyclin-dependent kinase inhibitor p27 expression. [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: August 2001
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: treatment
please see intervention description
Biological: trastuzumab
Day 1 4mg/kg IV 2 mg/kg IV weekly.
Other Name: Herceptin
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.
Other Name: OSI-774

Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Women aged > 18 years
  • Histologically documents metastatic breast cancer
  • HER2 positive using 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)
  • 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.
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Please refer to this study by its identifier: NCT00033514

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Genentech, Inc.
Principal Investigator: Carolyn Britten, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
Responsible Party: Jonsson Comprehensive Cancer Center Identifier: NCT00033514     History of Changes
Other Study ID Numbers: CDR0000069295, P30CA016042, UCLA-0106020, GENENTECH-OSI2365s, NCI-G02-2057
Study First Received: April 9, 2002
Last Updated: October 29, 2015
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses processed this record on November 27, 2015