LDE225 in Treating Patients With Stage II-III Estrogen Receptor- and HER2-Negative Breast Cancer
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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|
- Proportion of patients who are bone marrow DTC-negative after therapy [ Time Frame: at 6 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]95% confidence intervals using Cox proportional hazard regression
- Concordance of DTC determination by ICC or gene expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]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.
|Study Start Date:||April 2014|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01757327
|Contact: Cynthia Ma, M.D., Ph.D.||email@example.com|
|Contact: Rebecca Aft, M.D., Ph.D.||firstname.lastname@example.org|
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|St. Louis, Missouri, United States, 63110|
|Contact: Rebecca Aft, M.D., Ph.D. 314-747-0063 email@example.com|
|Contact: Cynthia Ma, M.D., Ph.D. 314-362-8903 firstname.lastname@example.org|
|Sub-Investigator: Ron Bose, M.D., Ph.D.|
|Sub-Investigator: Matthew Ellis, M.B., Ph.D.|
|Sub-Investigator: Michael Naughton, M.D.|
|Sub-Investigator: Steven Sorscher, M.D.|
|Sub-Investigator: Rama Suresh, M.D.|
|Sub-Investigator: Katherine Weilbaecher, M.D.|
|Sub-Investigator: Amy Cyr, M.D.|
|Sub-Investigator: Timothy Eberlein, M.D.|
|Sub-Investigator: William Gillanders, M.D.|
|Sub-Investigator: Julie Margenthaler, M.D.|
|Sub-Investigator: Erika Crouch, M.D.|
|Sub-Investigator: Shashikant Kuulkarni, Ph.D.|
|Sub-Investigator: Mark Watson, M.D., Ph.D.|
|Sub-Investigator: Cory Bernadt, M.D., Ph.D.|
|Sub-Investigator: Deborah Novack, M.D., Ph.D.|
|Sub-Investigator: Katherine Schwetye, M.D., Ph.D.|
|Sub-Investigator: Foluso Ademuyiwa, MD|
|Sub-Investigator: Adel Tabchy, M.D.|
|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|