LDE225 in Treating Patients With Stage II-III Estrogen Receptor- and HER2-Negative Breast Cancer

Phase 2

Withdrawn

• Conditions: Breast Neoplasms
• Interventions: Drug: Placebo; Drug: Erismodegib

• Registration Number: NCT01757327
• Lead Sponsor: Washington University School of Medicine

Brief Summary

This randomized phase II trial studies the effects of erismodegib (LDE225) on disseminated tumor cells (DTCs) in patients with stage III-III estrogen receptor (ER)-negative and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The presence of DTCs after completing treatment for breast cancer may be linked to recurrence of the disease. LDE225 may eliminate DTCs in bone marrow and reduce the risk of recurrence.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-12-20
• Study First Submitted QC: 2012-12-27
• Study First Posted: 2012-12-28
• Study Start: 2014-04
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-24
• Last Update Posted: 2015-04-27
• Primary Completion: 2016-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (placebo)	Placebo	Patients receive placebo PO daily and treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
Arm I (erismodegib [LDE225])	Erismodegib	400 mg daily and treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Proportion of patients who are bone marrow DTC-negative after therapy	at 6 months	Comparing LDE225 to placebo using a stratified Cochran-Mantel-Haenszel test for difference of proportions

Secondary Outcome Measures

Name	Time	Method
Disease-free survival (DFS)	2 years from initiation of study treatment	Defined as duration after surgery that the patient survives without signs or symptoms of cancer; analyzed using a stratified Cox proportional hazards model.
Overall Survival (OS)	2 years from initiation of study treatment	Defined as time from date of diagnosis to death of any cause or to last follow-up; analyzed using a stratified Cox proportional hazards model.
Ptch1 expression after treatment with LDE225 or placebo	At 6 months	Stratified, repeated measures ANOVA will be used to compare Ptch1 expression in the two treatment arms
Incidence of toxicities associated with LDE225 or placebo treatment	For 30 days following the last day of study treatment; up to 25 months	Toxicities described and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
Time to recurrence and death in DTC-negative patients and DTC-positive patients	2 years from initiation of study treatment	Cox regression will be used to compare time to recurrence or death in DTC-negative patients ineligible for randomization with those randomized to receive treatment
Time to recurrence and death in ICC negative versus ICC positive patients	2 years from initiation of treatment	95% confidence intervals using Cox proportional hazard regression
Concordance of DTC determination by ICC or gene expression	Baseline	Expressed using kappa statistics with 95% confidence intervals. McNemar's test will be used to test for a statistically significant difference between the proportion positive by ICC and gene expression.