Clinical trial NCT02212574: Study Assessing the Feasibility of a Surgery and Chemotherapy-Only in Children With Wnt Positive Medulloblastoma
Official title: Pilot Study Assessing the Feasibility of a Surgery and Chemotherapy-Only Approach in the Upfront Therapy of Children With Wnt Positive Standard Risk Medulloblastoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Medulloblastoma
Keywords: Wnt
Medulloblastoma
Chemotherapy
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: The Matthew Larson Foundation for Pediatric Brain Tumors
First posted: 2014-08-08
Enrollment: 6
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Participants enrolling on this study will receive standard of care chemotherapy for Wnt positive medulloblastoma without the radiation therapy or the weekly chemotherapy that is given during radiation therapy.

Detailed description: There will be 9 cycles of chemotherapy. There are two different kinds of cycles given. They are referred to as A and B.

Cycle A lasts for 6 weeks and Cycle B lasts for 4 weeks. B cycles are given after the completion of two A cycles.

Below are the details of the drugs and schedules for A and B cycles.

Cycle A (This cycle lasts 42 days)

* Lomustine (CCNU) is given by mouth on Day 1.
* Vincristine is given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, and 15.
* Cisplatin is given directly into a vein over 8 hours on Day 1

Cycle B (This cycle lasts 28 days)

* Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2.
* MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide and repeated at 3 and 6 hours.
* Vincristine is given directly into a vein directly into the vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 and 8.

You may also get a supportive care drug called a myeloid growth factor (filgrastim or pegfilgrastim). This drug will help your blood counts recover after the chemotherapy is given.

Eligibility criteria: Inclusion Criteria:

* Participants must have classical histology posterior fossa medulloblastoma as determined by institutional neuro-pathological evaluation.
* Sufficient pathologic material must be available for central analysis and review
* Tumors will be deemed Wnt positive if, at the time of central analysis, there is:
* Monosomy 6 as determined by array CGH
* Gene transcript detection by NanoString supporting Wnt+ medulloblastoma
* Absence of large-cell, anaplastic histology
* Nuclear b-catenin IHC will be determined, but not required for the diagnosis
* Absence of residual or disseminated disease as defined by the following criteria: Minimal residual disease as determined by post-operative imaging preferably performed within 48 hours of resection (and at most 28 days post-surgery), i.e. gross total resection or residual disease of \<1.5cm2 on post-operative imaging.

No evidence of metastatic disease in the brain, spine or cerebral spinal fluid (CSF). Assessments must include MRI imaging of the brain and spine with and without contrast and a lumbar puncture for CSF cytology

* Diagnostic imaging (pre and post contrast) must be forwarded to Dana-Farber Cancer Institute (DFCI) for central review to confirm eligibility
* Patients must not have had any radiation therapy or chemotherapy for medulloblastoma prior to study enrollment
* Patients must have a Lansky performance status of \>/=30 for children \</=10 years of age or a Karnofsky performance status of \> 30 for children \> 10 years of age.
* Participants must have normal organ and marrow function as defined below:
* Hemoglobin greater than 10 g/dL (can be transfused). Hemoglobin \<10 g/dL due to operative blood loss is permitted.
* Absolute neutrophil count \> 1.0x109/L
* Platelets \> 100,000/uL (non-transfused)
* Total bilirubin \<1.5 x upper limit normal
* SGOT (AST) or SGPT (ALT) \<2.5 x upper limit normal (ULN) for age
* Creatinine clearance or radioisotope GFR \>70 ml/min/1.73m2 or normal serum creatinine for patient's age and gender
* All females of child-bearing age must have a negative pregnancy test before being enrolled on study. All patients of child-bearing age must practice an effective method of birth control whilst undergoing chemotherapy on study.
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, lomustine, vincristine or cyclophosphamide.

Primary outcomes:
measure: Progression Free Survival
timeFrame: 3 years
Secondary outcomes:
measure: Patterns of Failure
timeFrame: 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital Hematology/Oncology
state: Arizona
city: Aurora
country: United States
facility: Children's Hospital Colorado Center for Cancer & Blood Disorders
state: Colorado
city: Orlando
country: United States
facility: M D Anderson Cancer Center-Orlando Pediatric Hematology/Oncology
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital Pediatric Hematology/Oncology
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta- Egleston Pediatric Neuro-Oncology
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H Lurie Children's Hospital of Chicago Hematology/Oncology
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine Pediatric Hematology/Oncology
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University Pediatric Hematology/Oncology
state: Oregon
city: Seattle
country: United States
facility: Seattle Children's Hospital Hematology/Oncology
state: Washington
city: Milwaukee
country: United States
facility: Childrens Hospital of Wisconsin (Medical College of Wisconsin)
state: Wisconsin
Study officials:
affiliation: Johns Hopkins University
name: Kenneth Cohen, MD
role: STUDY_CHAIR
References: