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

October 11, 2012
June 15, 2014
May 2013
August 2016   (final data collection date for primary outcome measure)
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.

Same as current
Complete list of historical versions of study NCT01708174 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)
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

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

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Medulloblastoma
Drug: LDE225
Experimental: relapsed after standard of care therapy
Relapsed after standard-of-care therapy including RT or children ≤ to 6 years who are RT-naive
Intervention: Drug: LDE225
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
December 2016
August 2016   (final data collection date for primary outcome measure)

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.
Both
Not Provided
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Australia,   Belgium,   Brazil,   Canada,   France,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   Poland,   Russian Federation,   Spain,   Sweden,   Switzerland,   United Kingdom
 
NCT01708174
CLDE225C2301
Yes
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP