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

Pilot Study Assessing the Feasibility of a Surgery and Chemotherapy-Only Approach in the Upfront Therapy of Children With Wnt Positive Standard Risk Medulloblastoma

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.

Study Overview

• Status: Terminated
• Conditions: Medulloblastoma
• Intervention / Treatment: Drug: Lomustine; Drug: Vincristine; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Mesna; Drug: Vincristine

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Childrens Hospital Hematology/Oncology
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado Center for Cancer & Blood Disorders
  • Florida
    • Orlando, Florida, United States, 32806
      • M D Anderson Cancer Center-Orlando Pediatric Hematology/Oncology
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital Pediatric Hematology/Oncology
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta- Egleston Pediatric Neuro-Oncology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H Lurie Children's Hospital of Chicago Hematology/Oncology
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine Pediatric Hematology/Oncology
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health and Science University Pediatric Hematology/Oncology
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital Hematology/Oncology
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Childrens Hospital of Wisconsin (Medical College of Wisconsin)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Chemotherapy; Chemotherapy Cycle A 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. This cycle lasts 42 days. Chemotherapy Cycle B 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.This cycle lasts 28 days

Drug: Lomustine; Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1.; Other Names: CCNU; Drug: 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.; Other Names: Oncovin; Drug: Cisplatin; Chemotherapy Cycle A Cisplatin is given directly into a vein over 8 hours on Day 1.; Other Names: Cisplatinum; Drug: Cyclophosphamide; Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2.; Other Names: Cytoxan; Drug: 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.; Other Names: Mesnex; Drug: 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.; Other Names: Oncovin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Matthew Larson Foundation
• Investigators: Study Chair: Kenneth Cohen, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2017
• Primary Completion (Actual): November 9, 2018
• Study Completion (Actual): November 9, 2018

Study Registration Dates

• First Submitted: July 7, 2014
• First Submitted That Met QC Criteria: August 6, 2014
• First Posted (Estimate): August 8, 2014

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: October 8, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Chemotherapy; Medulloblastoma; Wnt
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Medulloblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Cyclophosphamide; Cisplatin; Vincristine; Lomustine
• Other Study ID Numbers: J1403; NA_00091840 (Other Identifier: JHMIRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No