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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01708174
First received: October 11, 2012
Last updated: June 15, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Medulloblastoma
Drug: LDE225
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multi-center, Open-label, Single-arm Study of the Efficacy and Safety of Oral LDE225 in Patients With Hh-pathway Activated Relapsed Medulloblastoma

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR). (As per Tumor response guidelines and criteria for Medulloblastoma.

    ORR will be done by independent central review.



Secondary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    PFS is defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause

  • Overall response rate (ORR) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    As per Tumor response guidelines and criteria for Medulloblastoma. ORR will be done by local investigator assessment.

  • Duration of response (DoR) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    DoR is defined as the time from the first documented onset of confirmed PR or CR to the date of PD/relapse or death due to medulloblastoma.

  • Overall survival (OS) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    OS is defined as the time from date of randomization to date of death due to any cause.

  • Safety and tolerability of LDE225 treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Adverse and serious adverse events, clinically significant changes in hematology and chemistry values, assessment of physical and/or neurological examinations, vital signs, electrocardiograms, bone x-rays, dental x-rays (e.g., panorex or age appropriate dental x-ray), and dental exams (as appropriate for age)

  • Pharmacokinetics (Pk) - Cmin [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    PK of LDE225 and any relevant metabolites


Estimated Enrollment: 20
Study Start Date: May 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: relapsed after standard of care therapy
Relapsed after standard-of-care therapy including RT or children ≤ to 6 years who are RT-naive
Drug: LDE225

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    1. Karnofsky performance status score ≥ 50 for patients >16 years of age
    2. Lansky performance status score ≥ 50 for patients ≤ 16 years of age
  • Adequate bone marrow function as defined as:

    1. Peripheral absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    2. Platelet count ≥ 80 x 109/L
    3. Hemoglobin (Hgb) ≥ 9 g/dL
  • Serum CK ≤1.5 ULN

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01708174

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: James T. Courtney    205-934-1813    jtcourtney@uabmc.edu   
Principal Investigator: Louis B. Nabors         
United States, California
Loma Linda University Dept of Oncology Withdrawn
Loma Linda, California, United States, 92354
University of California at Los Angeles UCLA LeConte Location Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Jill Paroly    +1 310 825 4493    jparoly@mednet.ucla.edu   
Principal Investigator: Tom Belle Davidson         
Rady Children's Hospital Dept of Oncology Not yet recruiting
San Diego, California, United States, 92123
Contact: Theresa Vella    858-966-5118    tvella@rchsd.org   
Principal Investigator: John Crawford         
University of California San Francisco Dept of Pediatic Oncology Not yet recruiting
San Francisco, California, United States, 94101
Contact: Sharon Lee    415-514-3658    leess@peds.ucsf.edu   
Principal Investigator: Sabine Mueller         
United States, Connecticut
Yale University School of Medicine Dept of Oncology Withdrawn
New Haven, Connecticut, United States, 06520
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Dept Oncology Recruiting
Tampa, Florida, United States, 33612
Contact: Tremaine Meade    813-745-3951    Tremaine.meade@moffitt.org   
Principal Investigator: Peter Forsyth         
United States, Georgia
Children's Healthcare of Atlanta Dept of Oncology Not yet recruiting
Atlanta, Georgia, United States, 30342
Contact: Katherine Garrett    404-785-3535    katherine.garrett@choa.org   
Principal Investigator: Tobey MacDonald         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Dept of Oncology Recruiting
Chicago, Illinois, United States, 60611
Contact: Jamie Sovcik    312-227-4855    jsovcik@luriechildrens.org   
Principal Investigator: Stewart Goldman         
United States, Iowa
University of Iowa Hospitals & Clinics Dept of Oncology Recruiting
Iowa City, Iowa, United States, 52242
Contact: Joan Kempf    319-384-5280    joan-kempf@uiowa.edu   
Principal Investigator: Sue O'Dorisio         
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Dept Onc Recruiting
Baltimore, Maryland, United States, 21231
Contact: Anne DeLisa    410-955-0432    oncpharmacy@jhmi.edu   
Principal Investigator: Kenneth R. Cohen         
United States, Massachusetts
Dana Farber Cancer Institute SC-7 Recruiting
Boston, Massachusetts, United States, 02115
Contact: Nathan Pinches    617-632-6308    nathan_pinches@dfci.harvard.edu   
Principal Investigator: Mark W. Kieran         
United States, Missouri
Children's Mercy Hospital Dept of Oncology Not yet recruiting
Kansas City, Missouri, United States, 64108
Contact: Sara Soliman    816-855-1977    sjsoliman@cmh.edu   
Principal Investigator: Kathleen Neville         
United States, New York
Columbia University Medical Center- New York Presbyterian Dept of Oncology Recruiting
New York, New York, United States, 10032
Contact: Dan Otap    212-305-9858    do2267@columbia.edu   
Principal Investigator: Andrew B. Lassman         
United States, Ohio
Cincinnati Children's Hospital Medical Center Division of Hema/Onco. Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Courtney Blank    513-636-9419    courtney.blank@cchmc.org   
Principal Investigator: Mariko DeWire         
University Hospitals of Cleveland Dept of Oncology Not yet recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Barbara Calabro    216-844-6054    barbara.calabro@UHhospitals.org   
Principal Investigator: Andrew Sloan         
United States, Pennsylvania
The Childrens Hospital of Philadelphia Dept of Oncology Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ratnakar Patti    267-426-5503    pattir@email.chop.edu   
Principal Investigator: Jane Minturn         
Children's Hospital of Pittsburgh Dept of Oncology Recruiting
Pittsburgh, Pennsylvania, United States, 15213-2583
Contact: Judith Cawley    412-692-8047    judith.cawley2@chp.edu   
Principal Investigator: Regina Jakacki         
United States, Tennessee
Vanderbilt University Medical Center Dept of Oncology Recruiting
Nashville, Tennessee, United States, 37232
Contact: Wendy Cooper    615-936-3064    wendy.cooper@vanderbilt.edu   
Principal Investigator: Paul L. Moots         
United States, Texas
Children's Medical Center of Dallas SC Not yet recruiting
Dallas, Texas, United States, 75235
Contact: Shahenaaz Sunderji    214-456-2382    shahenaaz.sunderji@childrens.com   
Principal Investigator: Ted Laetsch         
UT Southwestern Clinical Trials Office SC - CLDE225C2301 Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Penny Currykoski    214-633-1825    penny.currykosky@utsouthwestern.edu   
Principal Investigator: Edward Pan         
University of Texas/MD Anderson Cancer Center SC-3 Recruiting
Houston, Texas, United States, 77030-4009
Contact: Jiyuan Ni    713-745-5769    jni@mdanderson.org   
Principal Investigator: Marta Penas-Prado         
United States, Washington
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Dept Oncology Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Dione Froman    206-884-1214    dione.froman@seattlechildrens.org   
Principal Investigator: Sarah Leary         
Australia, New South Wales
Novartis Investigative Site Withdrawn
Randwick, New South Wales, Australia, 2130
Australia, Queensland
Novartis Investigative Site Recruiting
Herston, Queensland, Australia, 4029
Australia, Western Australia
Novartis Investigative Site Recruiting
Perth, Western Australia, Australia, 6001
Belgium
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Brazil
Novartis Investigative Site Withdrawn
Rio de Janiero, RJ, Brazil, 20231-050
Novartis Investigative Site Withdrawn
Porto Alegre, RS, Brazil, 90035-903
Novartis Investigative Site Withdrawn
Barretos, SP, Brazil, 14784-400
Novartis Investigative Site Withdrawn
Sao Paulo, SP, Brazil, 05403-000
Novartis Investigative Site Active, not recruiting
Sao Paulo, SP, Brazil
Novartis Investigative Site Withdrawn
São Paulo, SP, Brazil, 08270-070
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 2M9
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 1X8
France
Novartis Investigative Site Recruiting
Bordeaux, Aquitaine, France, 33076
Novartis Investigative Site Recruiting
Angers Cedex 1, France, 49033
Novartis Investigative Site Recruiting
Lille Cedex, France, 59020
Novartis Investigative Site Withdrawn
Lyon Cedex, France, 69373
Novartis Investigative Site Recruiting
Marseille Cedex 5, France, 13385
Novartis Investigative Site Withdrawn
Nancy, France, 54035
Novartis Investigative Site Recruiting
Paris, France, 75231
Novartis Investigative Site Withdrawn
Paris Cedex 13, France, 75651
Novartis Investigative Site Withdrawn
Poitiers, France, 86000
Novartis Investigative Site Recruiting
Toulouse Cedex 9, France, 31059
Novartis Investigative Site Recruiting
Vandoeuvre les Nancy, France, 54511
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site Recruiting
Augsburg, Germany, 86156
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Novartis Investigative Site Not yet recruiting
Frankfurt, Germany, 60590
Novartis Investigative Site Recruiting
Freiburg, Germany, 79106
Novartis Investigative Site Recruiting
Hamburg, Germany, 20246
Novartis Investigative Site Not yet recruiting
Heidelberg, Germany, 69120
Novartis Investigative Site Withdrawn
Muenster, Germany, 48149
Novartis Investigative Site Recruiting
Regensburg, Germany, 93053
Novartis Investigative Site Not yet recruiting
Regensburg, Germany, 93053
Novartis Investigative Site Recruiting
Stuttgart, Germany, 70176
Hungary
Novartis Investigative Site Not yet recruiting
Budapest, Hungary, 1094
Israel
Novartis Investigative Site Recruiting
Petach-Tikva, Israel, 49202
Novartis Investigative Site Recruiting
Tel-Aviv, Israel, 64239
Italy
Novartis Investigative Site Recruiting
Bologna, BO, Italy, 40139
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00165
Novartis Investigative Site Recruiting
Torino, TO, Italy, 101126
Novartis Investigative Site Recruiting
Torino, TO, Italy, 10126
Netherlands
Novartis Investigative Site Recruiting
Rotterdam, Netherlands, 3015 GJ
Novartis Investigative Site Recruiting
Rotterdam, Netherlands, 3075 EA
Poland
Novartis Investigative Site Not yet recruiting
Warsaw, Poland, 04-730
Russian Federation
Novartis Investigative Site Recruiting
Moskow, Russia, Russian Federation, 117198
Novartis Investigative Site Not yet recruiting
St.Petersburg, Russia, Russian Federation, 191014
Spain
Novartis Investigative Site Recruiting
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Esplugues de Llobregat, Catalunya, Spain, 08950
Novartis Investigative Site Recruiting
Valencia, Comunidad Valenciana, Spain, 46026
Novartis Investigative Site Recruiting
Madrid, Spain, 28009
Novartis Investigative Site Recruiting
Madrid, Spain, 28046
Novartis Investigative Site Withdrawn
Madrid, Spain, 28050
Sweden
Novartis Investigative Site Recruiting
Goteborg, Sweden, 413 45
Novartis Investigative Site Withdrawn
Göteborg, Sweden, SE-416 85
Novartis Investigative Site Recruiting
Lund, Sweden, SE-221 85
Novartis Investigative Site Withdrawn
Stockholm, Sweden, SE-171 76
Novartis Investigative Site Recruiting
Stockholm, Sweden, SE-171 76
Novartis Investigative Site Recruiting
Umeå, Sweden, SE-901 85
Novartis Investigative Site Withdrawn
Uppsala, Sweden, SE-751 85
Switzerland
Novartis Investigative Site Not yet recruiting
Luzern, CH, Switzerland, 6000
Novartis Investigative Site Not yet recruiting
Luzern, Switzerland, 6000
Novartis Investigative Site Withdrawn
Zuerich, Switzerland, 8091
Novartis Investigative Site Recruiting
Zürich, Switzerland, 8032
United Kingdom
Novartis Investigative Site Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Novartis Investigative Site Not yet recruiting
Bath, United Kingdom, BS2 8BJ
Novartis Investigative Site Recruiting
Birmingham, United Kingdom, B4 6NH
Novartis Investigative Site Recruiting
Glasgow, United Kingdom, G3 8SJ
Novartis Investigative Site Withdrawn
Glasgow, United Kingdom, G12 0YN
Novartis Investigative Site Recruiting
Leeds, United Kingdom, LS9 7TF
Novartis Investigative Site Recruiting
London, United Kingdom, WC1N 3JH
Novartis Investigative Site Not yet recruiting
Manchester, United Kingdom, M20 9BX
Novartis Investigative Site Recruiting
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01708174     History of Changes
Other Study ID Numbers: CLDE225C2301
Study First Received: October 11, 2012
Last Updated: June 15, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Spain: Spanish Agency of Medicines

Keywords provided by Novartis:
medulloblastoma,
relapsed,
pediatric,
children,
adults,
Hh pathway inhibitor,
LDE225

Additional relevant MeSH terms:
Medulloblastoma
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

ClinicalTrials.gov processed this record on September 16, 2014