LDE225 for Patients With PTCH1 or SMO Mutated Tumors (SIGNATURE)

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

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

Study Overview

• Status: Terminated
• Conditions: PTCH1 or SMO Activated Solid and Hematologic Tumors
• Intervention / Treatment: Drug: LDE225

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center UC Davis Cancer (3)
  • Colorado
    • Greenwood Village, Colorado, United States
      • Rocky Mountain Cancer Centers RMCC - Aurora
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital of Chicago Developmental Therapeutics
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, P.A. Southdate Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation Cleveland Clinic (19)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Research Sanford Health
  • Texas
    • Houston, Texas, United States, 77024
      • Oncology Consultants Oncology Group
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center Intermountain Healthcare
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Seattle Cancer Care Alliance Skagit Valley Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: December 1, 2013
• First Submitted That Met QC Criteria: December 1, 2013
• First Posted (Estimate): December 6, 2013

Study Record Updates

• Last Update Posted (Estimate): May 2, 2016
• Last Update Submitted That Met QC Criteria: April 25, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: NSCLC; Solid tumor malignancy,; hematologic malignancy,; mutation, translocations,; signature,; PTCH1,; SMO,; LDE225,; endometrial cancer,; colon cancer,; bladder,
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CLDE225XUS20