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A Phase III, Multi-center, Open-label, Randomized, Controlled Study of the Efficacy and Safety of Oral LDE225 Versus Temozolomide in Patients With Hh-pathway Activated Relapsed Medulloblastoma


Phase 3
N/A
N/A
Open (Enrolling)
Both
Medulloblastoma

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Trial Information

A Phase III, Multi-center, Open-label, Randomized, Controlled Study of the Efficacy and Safety of Oral LDE225 Versus Temozolomide in Patients With Hh-pathway Activated Relapsed Medulloblastoma


Inclusion Criteria:



- Patients with histologically confirmed diagnosis of MB, who have experienced relapse
or progression after standard-of-care therapy including radiotherapy with no prior
exposure to TMZ therapy. 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 ≥ 100 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.

- History of hypersensitivity reaction to dacarbazine (DTIC), TMZ or any of its
components.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response rate (ORR)

Outcome Description:

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.

Outcome Time Frame:

8 weeks

Safety Issue:

No

Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

CLDE225C2301

NCT ID:

NCT01708174

Start Date:

May 2013

Completion Date:

November 2016

Related Keywords:

  • Medulloblastoma
  • medulloblastoma,
  • relapsed,
  • pediatric,
  • children,
  • adults,
  • Hh pathway inhibitor,
  • temozolomide,
  • LDE225
  • Medulloblastoma

Name

Location

University of Alabama at BirminghamBirmingham, Alabama  35294-3300
MD Anderson Cancer Center/University of Texas SC-3Houston, Texas  77030-4009
University of California at Los Angeles UCLA LeConte LocationLos Angeles, California  90095
Loma Linda University Dept of OncologyLoma Linda, California  92354
Rady Children's Hospital Dept of OncologySan Diego, California  92123
University of California San Francisco Dept of Pediatic OncologySan Francisco, California  94101
Yale University School of Medicine Dept of OncologyNew Haven, Connecticut  06520
H. Lee Moffitt Cancer Center & Research Institute Dept OncologyTampa, Florida  33612
Children's Healthcare of Atlanta Dept of OncologyAtlanta, Georgia  30342
Ann & Robert H. Lurie Children's Hospital of Chicago Dept of OncologyChicago, Illinois  60611
University of Iowa Hospitals & Clinics Dept of OncologyIowa City, Iowa  52242
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Dept OncBaltimore, Maryland  21231
Dana Farber Cancer Institute SC-7Boston, Massachusetts  02115
Children's Mercy Hospital Dept of OncologyKansas City, Missouri  64108
Columbia University Medical Center- New York Presbyterian Dept of OncologyNew York, New York  10032
Cincinnati Children's Hospital Medical Center Dept of Oncology1Cincinnati, Ohio  45229-3039
University Hospitals of Cleveland Dept of OncologyCleveland, Ohio  44106-5065
The Childrens Hospital of Philadelphia Dept of OncologyPhiladelphia, Pennsylvania  19104
Children's Hospital of Pittsburgh Dept of OncologyPittsburgh, Pennsylvania  15213-2583
Vanderbilt University Medical Center Dept of OncologyNashville, Tennessee  37232
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Dept OncologySeattle, Washington  98109-1023