LDE225 for Patients With PTCH1 or SMO Mutated Tumors

Study Overview
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Brief Summary
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The purpose of this signal seeking study is to determine whether treatment with LDE225 demonstrates sufficient efficacy in hedgehog pathway-mutated solid tumors and/or hematologic malignancies to warrant further study

Official Title
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Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module - 5 LDE225 for Patients With PTCH1 or SMO Mutated Tumors

Conditions
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PTCH1 or SMO Activated Solid and Hematologic Tumors

Intervention / Treatment
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* Drug: LDE225


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has confirmed diagnosis of a select solid tumor (except medulloblastoma, basal cell carcinoma and pancreatic adenocarcinoma) or hematological malignancy (except CML, ALL and AML). Patient has pre-identified tumor with a PTCH1 or SMO mutation. Patient has received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission. Patient has progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Exclusion Criteria: Patients has received prior treatment with LDE225. Patients has neuromuscular disorders associated with elevated CK (i.e. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis Patients has primary CNS tumor or CNS tumor involvement Patient has received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDE225<br>LDE225 800 mg (hard gelatin capsules) will be administered orally once daily on a continuous dosing schedule. | Drug: LDE225<br>* LDE225 800 mg (hard gelatin capsules) will be administered orally once daily on a continuous dosing schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Overall Response (ORR) and Clinical Benefit (CBR) | Clinical benefit rate (CBR) Number and percentage of subjects with CBR (responses of CR, PR or SD ≥ 16 weeks) as assessed by investigator was reported for all patients along with 95% exact confidence interval (CI). Overall Response Rate (ORR) Overall response was to be determined by investigator assessment for each tumor in the study. For subjects with solid tumors, the assessment criteria was RECIST 1.1 and included responses of CR and/or PR. The number and percentage of subjects for different categories of overall response (e.g., for solid tumors - CR, PR, SD, PD, Not Evaluable) were to be provided for solid tumors, and each hematological tumor type (if applicable). Ninety-five percent (95%) exact CI was to be provided for the response rate(s) (e.g., for solid tumors - CRn and/or PR) as well. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Timing and Estimated Rate for Progression-free Survival (PFS) - Full Analysis Set | Progression-free survival (PFS) is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 30 days of last dose. If a subject has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. | 4 months | 
| Kaplan-Meier Estimates of Progression Free Survival (PFS )Timing, Months |  | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumor malignancy,, hematologic malignancy,, mutation, translocations,, signature,, PTCH1,, SMO,, LDE225,, endometrial cancer,, colon cancer,, bladder,, NSCLC