RO4929097 and Letrozole in Treating Post-Menopausal Women With Hormone Receptor-Positive Stage II or Stage III Breast Cancer



Status:Archived
Conditions:Breast Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any
Updated:7/1/2011
Start Date:November 2010

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A Phase Ib Neoadjuvant Study of the Gamma Secretase Inhibitor (RO4929097) in Combination With the Aromatase Inhibitor Letrozole in Post-Menopausal Women With Stage II/III Hormone Receptor-Positive Breast Cancer


RATIONALE: RO4929097 may stop the growth of tumor cells by blocking some of the enzymes
needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone
therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor
cells. Giving RO4929097 together with letrozole may be an effective treatment for breast
cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of RO4929097 when
given together with letrozole in treating post-menopausal women with stage II or stage III
breast cancer.


OBJECTIVES:

Primary

- To establish the maximum-tolerated dose and the recommended phase II dose of
gamma-secretase inhibitor RO4929097 (RO4929097) in combination with letrozole in
post-menopausal women with hormone receptor-positive stage II or III breast cancer.

- To assess the safety of this regimen in these patients.

Secondary

- To evaluate the pharmacokinetics of this regimen, taking into consideration the
induction of CYP3A4, in these patients.

- To characterize the pharmacodynamic effects of letrozole prior to and during
administration of RO4929097 with attention to suppression of estradiol and estrone
levels.

- To describe the pharmacodynamic effects of letrozole with or without RO4929097 on the
NOTCH pathway, proliferation, angiogenesis, stromal cell infiltration/pathways, and
comprehensive genomic analysis in tumor tissue of these patients.

- To describe the response, including clinical complete or partial objective response,
pathological complete response, and attainment of pathologic stage 0 or I status in
these patients.

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

Patients receive oral letrozole once daily on days 1-21. Beginning in course 2, patients
also receive oral RO4929097 on days 1-3, 8-10, and 15-18. Treatment repeats every 21 days
for 6 courses in the absence of disease progression or unacceptable toxicity.

Beginning 1 week after completion of neoadjuvant therapy, patients undergo surgery or tumor
biopsy. Patients continue to receive oral letrozole once daily during surgery and for an
additional 4 weeks.

Blood and tumor tissue samples are collected at baseline and periodically during study for
pharmacokinetics, pharmacodynamics, and correlative studies.

After completion of study therapy, patients are followed up for 1 month and then every 6
months for 5 years.


We found this trial at
2
sites
200 Lothrop St
Pittsburgh, Pennsylvania 15213
University of Pittsburgh Medical Center UPMC is one of the leading nonprofit health systems in...
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1802 6th Avenue South
Birmingham, Alabama 35294
(205) 934-4011
UAB Comprehensive Cancer Center One of the nation’s leading cancer research and treatment centers, the...
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Birmingham, AL
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