A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)

NCT01708174 | Completed Phase 2 Results

• 1 other identifier: CLDE225C2301
• Study Type: interventional
• Target: 22
• Locations: 13 countries
• Sites: 41

Brief Summary

This Phase II study evaluated the safety and efficacy of LDE225 in adult and pediatric patients with Hh-pathway activated, relapsed MB.

Conditions

Medulloblastoma

Keywords

medulloblastoma,; relapsed,; pediatric,; children,; adults,; Hh pathway inhibitor,; LDE225

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016

  ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). Assessments after crossover were not included for TMZ participants.

  from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016

Secondary Outcomes (6)

• Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016

  from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016

• PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016

  from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016

• Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016

  from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016

• Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016

  from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016

• Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016

  from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016

Study Arms (2)

Sonidegib (LDE225)

EXPERIMENTAL

600 mg orally for adults and 500 mg/m2 orally for children

Drug: LDE225

Temozolamide (TMZ)

ACTIVE COMPARATOR

150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study.

Drug: TMZ

Interventions

LDE225 DRUG

Sonidegib for oral suspension was supplied in amber glass bottles. Sonidegib oral suspension was combined with the supplied reconstitution vehicle to a final concentration of 50 mg/mL.

Sonidegib (LDE225)

TMZ DRUG

Temozolomide capsules were obtained locally by the Investigator

Temozolamide (TMZ)

Eligibility Criteria

• Age: 4 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed diagnosis of MB, who have experienced relapse or progression after standard-of-care therapy including radiotherapy. Patients currently receiving steroids must have been on a stable (or decreasing) dose for at least 5 days before initiating study therapy.
• Only patients with a test result, using the 5-gene Hh signature assay, indicating Hhpathway activated MB are eligible for this study. All available tumor material obtained at any time during the course of the patient's disease should be submitted for these analyses
• At least one measurable lesion defined as lesion(s) that can be accurately measured in at least two dimensions and is ≥ 10 mm in each dimension by Gadolinium (Gd)-MRI, irrespective of slice thickness/reconstruction interval, for CNS lesions and CT or MRI (with or without contrast) for non-CNS lesions. All patients with CNS lesions must have a brain MRI with and without gadolinium and a spine MRI with gadolinium within 2 weeks prior to first dose of study treatment.
• Performance Status corresponding to ECOG score of 0, 1, or 2:
• Karnofsky performance status score ≥ 50 for patients \>16 years of age
• Lansky performance status score ≥ 50 for patients ≤ 16 years of age
• Adequate bone marrow function as defined as:
• Peripheral absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 80 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Serum CK ≤1.5 ULN

You may not qualify if:

• Prior treatment with a Smoothened inhibitor Systemic anticancer treatment within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies).
• Focal radiation therapy within 4 weeks before first dose of study treatment, or full spinal radiotherapy within 3 months before first dose of study treatment.
• Patients who have neuromuscular disorders that are associated with elevated CK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
• Patients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 or are metabolized by CYP2B6 and CYP2C9, that have narrow therapeutic indices that cannot be discontinued at least 2 weeks before first dose of study treatment and for the duration of the study
• Patients receiving unstable or increasing doses of corticosteroids. If patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms, dose must have been stabilized (or decreasing) for at least 5 days before first dose of study treatment.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (41)

Ann & Robert H. Lurie Children Dept of Oncology

Chicago, Illinois, 60611, United States

Location

Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Dept Onc

Baltimore, Maryland, 21231, United States

Location

Dana Farber Cancer Institute SC-7

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center- New York Presbyterian Dept of Oncology

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center Division of Hema/Onco.

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Pittsburgh Dept of Oncology

Pittsburgh, Pennsylvania, 15213-2583, United States

Location

University of Texas/MD Anderson Cancer Center SC-3

Houston, Texas, 77030-4009, United States

Location

Seattle Cancer Care Alliance Dept Oncology

Seattle, Washington, 98105, United States

Location

Novartis Investigative Site

Herston, Queensland, 4029, Australia

Location

Novartis Investigative Site

Perth, Western Australia, 6840, Australia

Location

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1X8, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 1Z6, Canada

Location

Novartis Investigative Site

Bordeaux, Aquitaine, 33076, France

Location

Novartis Investigative Site

Angers, 49033, France

Location

Novartis Investigative Site

Lille, 59020, France

Location

Novartis Investigative Site

Paris, 75231, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Augsburg, 86156, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Bologna, BO, 40139, Italy

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Roma, RM, 00165, Italy

Location

Novartis Investigative Site

Torino, TO, 101126, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Rotterdam, 3015 CN, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3075 EA, Netherlands

Location

Novartis Investigative Site

Moscow, Russia, 117198, Russia

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Esplugues de Llobregat, Catalonia, 08950, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46026, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Gothenburg, 413 45, Sweden

Location

Novartis Investigative Site

Zurich, 8032, Switzerland

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

Location

MeSH Terms

Conditions

Medulloblastoma; Recurrence

Interventions

sonidegib

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2012
• First Posted: October 16, 2012
• Study Start: May 6, 2013
• Primary Completion: October 5, 2016
• Study Completion: October 5, 2016
• Last Updated: August 11, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-08

Locations

DE (3); CA (2); CH (1); IT (5); RU (1); US (8); AU (2); BR (1); NL (2); ES (6); SE (1); FR (7); GB (2)