A Phase I/II Trial of Herceptin and ZD1839 (Iressa, NSC #715055, IND#61187) in Patients With Metastatic Breast Cancer That Overexpresses HER2/Neu (erbB-2)

National Cancer Institute (NCI)1 site in 1 country132 target enrollmentFebruary 2002

Overview

Brief Summary

This phase II trial is studying how well giving trastuzumab together with gefitinib works in treating patients with HER2-positive breast cancer. The monoclonal antibody trastuzumab can locate breast cancer cells that have HER2 on their surface and either kill them or deliver tumor-killing substances to them without harming normal cells. Biological therapies such as gefitinib may also interfere with the growth of tumor cells and may enhance the effects of trastuzumab. Combining trastuzumab with gefitinib may be an effective treatment for metastatic breast cancers with high amounts of HER2

Detailed Description

PRIMARY OBJECTIVES: I. Determine the response rate, duration of response, and time to progression in patients with metastatic breast cancer that overexpresses HER2-neu treated with trastuzumab (Herceptin) and gefitinib. II. Determine the phase II dose of gefitinib when given in combination with trastuzumab in these patients. III. Determine the toxicity of this regimen in these patients. IV. Determine the 3- and 6-month progression-free survival of patients treated with this regimen. V. Correlate response rates with plasma levels of circulating HER2 and tumor levels of epidermal growth factor receptor, activated HER2, and HER2 receptors, as measured by immunohistochemistry and/or fluorescent in situ hybridization (FISH), in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of gefitinib. The phase I portion of this study was open in only 5 ECOG institutions. The phase I portion has been completed, and the study is being opened in all ECOG-affiliated institutions. Phase I (completed): Patients receive trastuzumab (Herceptin) IV over 30-90 minutes once weekly and oral gefitinib once daily beginning on day 1. Cohorts of 3-6 patients receive escalating doses of gefitinib 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 established, additional patients are accrued to the phase II portion of the study and are treated at that dose. Phase II: Patients receive oral gefitinib once daily (at the MTD established in phase I) and trastuzumab IV weekly until week 24, at which time trastuzumab is given every 3 weeks (with daily gefitinib) until disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until 2 years from study entry.

Registry

clinicaltrials.gov

Start Date

February 2002

End Date

July 2007

Last Updated

13 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

National Cancer Institute (NCI)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed metastatic adenocarcinoma of the breast
•Patients may have had or not had standard first-line chemotherapy for the treatment of metastatic disease
•Overexpression of HER2-neu (HER2 3+ by immunohistochemistry or gene amplification as measured by fluorescent in situ hybridization)
•Measurable disease
•Patients with no prior adjuvant chemotherapy may have failed or not failed first-line chemotherapy for metastatic disease
•No more than 2 prior systemic chemotherapy regimens for metastatic disease
•Relapse while receiving or within 6 months of completion of adjuvant chemotherapy is considered failure of 1 regimen for metastatic disease
•No untreated brain metastases or brain metastases undergoing radiotherapy
•Previously treated brain metastasis that has responded to radiotherapy and/or surgery allowed if not sole site of measurable disease
•Hormone receptor status:

Exclusion Criteria

Not provided

Arms & Interventions

Treatment (trastuzumab, gefitinib)

Phase I (completed): Patients receive trastuzumab (Herceptin) IV over 30-90 minutes once weekly and oral gefitinib once daily beginning on day 1. Cohorts of 3-6 patients receive escalating doses of gefitinib 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 established, additional patients are accrued to the phase II portion of the study and are treated at that dose. Phase II: Patients receive oral gefitinib once daily (at the MTD established in phase I) and trastuzumab IV weekly until week 24, at which time trastuzumab is given every 3 weeks (with daily gefitinib) until disease progression or unacceptable toxicity.

Intervention: trastuzumab

Treatment (trastuzumab, gefitinib)

Phase I (completed): Patients receive trastuzumab (Herceptin) IV over 30-90 minutes once weekly and oral gefitinib once daily beginning on day 1. Cohorts of 3-6 patients receive escalating doses of gefitinib 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 established, additional patients are accrued to the phase II portion of the study and are treated at that dose. Phase II: Patients receive oral gefitinib once daily (at the MTD established in phase I) and trastuzumab IV weekly until week 24, at which time trastuzumab is given every 3 weeks (with daily gefitinib) until disease progression or unacceptable toxicity.

Intervention: gefitinib

Treatment (trastuzumab, gefitinib)

Phase I (completed): Patients receive trastuzumab (Herceptin) IV over 30-90 minutes once weekly and oral gefitinib once daily beginning on day 1. Cohorts of 3-6 patients receive escalating doses of gefitinib 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 established, additional patients are accrued to the phase II portion of the study and are treated at that dose. Phase II: Patients receive oral gefitinib once daily (at the MTD established in phase I) and trastuzumab IV weekly until week 24, at which time trastuzumab is given every 3 weeks (with daily gefitinib) until disease progression or unacceptable toxicity.

Intervention: laboratory biomarker analysis