RO4929097 And Exemestane in Treating Pre- and Postmenopausal Patients With Advanced or Metastatic Breast Cancer

Stage IV Breast Cancer Clinical Trial

Official title: A Phase I Dose Escalation Trial of RO4929097 Administered in Combination With Exemestane in Pre- and Postmenopausal Patients With ER + Metastatic Breast Cancer

Status Terminated

Clinical Trial Summary

This partially randomized phase I trial is studying the side effects and the best dose of RO4929097 when given together with exemestane and to see how well it works compared to exemestane alone in treating premenopausal and postmenopausal patients with advanced or metastatic breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by lowering the amount of estrogen the body makes. RO4929097 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving exemestane together with RO4929097 may kill more breast cancer cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Determine the maximum-tolerated dose of gamma-secretase inhibitor RO4929097 (RO4929097) in combination with exemestane in pre- and postmenopausal patients with estrogen receptor-positive (ER+) advanced or metastatic breast cancer.

II. Determine the safety and tolerability of this regimen in these patients. III. Determine the progression-free survival of patients treated with exemestane with vs without RO4929097.

SECONDARY OBJECTIVES:

I. Determine the overall tumor response rate in patients treated with these regimens.

II. Determine the overall survival of patients treated with these regimens. III. Determine the safety of these regimens in these patients. IV. Determine the quality of life of patients treated with these regimens. V. Identify biomarkers of response to treatment or toxicity.

OUTLINE: This is a multicenter, phase I, dose-escalation study of gamma-secretase inhibitor RO4929097.

Patients receive oral exemestane once daily on days 1-21 and oral gamma-secretase inhibitor RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are stratified according to menopausal status (pre- vs postmenopausal) and visceral disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive exemestane as in phase I and oral gamma-secretase inhibitor RO4929097 at the MTD determined in phase I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive exemestane as in arm I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

In addition to exemestane, pre-menopausal patients receive goserelin subcutaneously every 28 days. Patients may undergo blood and tissue sample collection for correlative studies.

Patients may complete quality-of-life questionnaires at baseline and periodically during study using the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B).

After completion of study therapy, patients are followed up for 4 weeks and then every 6 months thereafter. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Carcinoma
• Estrogen Receptor Positive
• HER2/Neu Negative
• Male Breast Carcinoma
• Recurrent Breast Carcinoma
• Stage IIIB Breast Cancer
• Stage IIIC Breast Cancer
• Stage IV Breast Cancer

• NCT number: NCT01149356
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Terminated
• Phase: Phase 1
• Start date: October 2010
• Completion date: April 2013