LDE225 in Treating Patients With Stage II-III Estrogen Receptor- and HER2-Negative Breast Cancer
|ClinicalTrials.gov Identifier: NCT01757327|
Recruitment Status : Withdrawn (Poor accrual)
First Posted : December 28, 2012
Last Update Posted : April 27, 2015
|Condition or disease||Intervention/treatment||Phase|
|Breast Neoplasms||Drug: Erismodegib Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized Placebo-Controlled Phase II Trial Evaluating the Effect of Hedgehog Inhibitor LDE225 on Bone Marrow Disseminated Tumor Cells in Women With Early Stage Estrogen Receptor Negative and HER2 Negative Breast Cancer|
|Study Start Date :||April 2014|
|Estimated Primary Completion Date :||December 2016|
|Estimated Study Completion Date :||December 2019|
Experimental: Arm I (erismodegib [LDE225])
400 mg daily and treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
Placebo Comparator: Arm II (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.
Other Name: PLCB
- Proportion of patients who are bone marrow DTC-negative after therapy [ Time Frame: at 6 months ]Comparing LDE225 to placebo using a stratified Cochran-Mantel-Haenszel test for difference of proportions
- Disease-free survival (DFS) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 2 years from initiation of treatment ]95% confidence intervals using Cox proportional hazard regression
- Concordance of DTC determination by ICC or gene expression [ Time Frame: 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01757327
|Principal Investigator:||Cynthia Ma, M.D., Ph.D.||Washington University School of Medicine|
|Principal Investigator:||Rebecca Aft, M.D., Ph.D.||Washington University School of Medicine|