Study Assessing the Feasibility of a Surgery and Chemotherapy-Only in Children With Wnt Positive Medulloblastoma

Medulloblastoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02212574
• Other study ID #: J1403
• Secondary ID: NA_00091840
• Status: Terminated
• Phase: Early Phase 1
• Start date: April 4, 2017
• Est. completion date: November 9, 2018

Study information

• Verified date: October 2021
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: November 9, 2018
• Est. primary completion date: November 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Medulloblastoma

Intervention

Drug:
• Lomustine
Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1.
• Vincristine
Chemotherapy Cycle A 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
Chemotherapy Cycle A Cisplatin is given directly into a vein over 8 hours on Day 1.
• Cyclophosphamide
Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2.
• Mesna
Chemotherapy Cycle B 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
Chemotherapy Cycle B 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.

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta- Egleston Pediatric Neuro-Oncology	Atlanta	Georgia
United States	Children's Hospital Colorado Center for Cancer & Blood Disorders	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Ann and Robert H Lurie Children's Hospital of Chicago Hematology/Oncology	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Childrens Hospital of Wisconsin (Medical College of Wisconsin)	Milwaukee	Wisconsin
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	M D Anderson Cancer Center-Orlando Pediatric Hematology/Oncology	Orlando	Florida
United States	Phoenix Childrens Hospital Hematology/Oncology	Phoenix	Arizona
United States	Oregon Health and Science University Pediatric Hematology/Oncology	Portland	Oregon
United States	Washington University School of Medicine Pediatric Hematology/Oncology	Saint Louis	Missouri
United States	All Children's Hospital Pediatric Hematology/Oncology	Saint Petersburg	Florida
United States	Seattle Children's Hospital Hematology/Oncology	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Matthew Larson Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	To determine the feasibility of treating newly diagnosed children with non-metastatic, standard risk, Wnt positive medulloblastoma with a chemotherapy-only approach. Primary outcome measure of this study will be progression-free survival; the number of participants who with progression free survival.	3 years
Secondary	Patterns of Failure	To evaluate the patterns of failure in those children that do not have progressive disease, progression free survival and overall survival.	3 years