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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: Matthew Larson Foundation
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Medulloblastoma	Drug: Lomustine; Drug: Vincristine; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Mesna	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 13 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 7, 2016
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: May 2022

Arms and Interventions

Arm

Intervention/treatment

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 Name: 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 Name: Oncovin; Drug: Cisplatin; Chemotherapy Cycle A Cisplatin is given directly into a vein over 8 hours on Day 1.; Other Name: Cisplatinum; Drug: Cyclophosphamide; Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2.; Other Name: 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 Name: 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 Name: Oncovin

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival [ Time Frame: 3 years ]
   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.

Secondary Outcome Measures :

1. Patterns of Failure [ Time Frame: 3 years ]
   To evaluate the patterns of failure in those children that do not have progressive disease, progression free survival and overall survival.

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

Phoenix Childrens Hospital Hematology/Oncology

Phoenix, Arizona, United States, 85016-7710

United States, Colorado

Children's Hospital Colorado Center for Cancer & Blood Disorders

Aurora, Colorado, United States, 80045

United States, Florida

M D Anderson Cancer Center-Orlando Pediatric Hematology/Oncology

Orlando, Florida, United States, 32806

All Children's Hospital Pediatric Hematology/Oncology

Saint Petersburg, Florida, United States, 33701

United States, Georgia

Children's Healthcare of Atlanta- Egleston Pediatric Neuro-Oncology

Atlanta, Georgia, United States, 30322

United States, Illinois

Ann and Robert H Lurie Children's Hospital of Chicago Hematology/Oncology

Chicago, Illinois, United States, 60611

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Missouri

Washington University School of Medicine Pediatric Hematology/Oncology

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27705

United States, Ohio

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

United States, Oregon

Oregon Health and Science University Pediatric Hematology/Oncology

Portland, Oregon, United States, 97239-3098

United States, Washington

Seattle Children's Hospital Hematology/Oncology

Seattle, Washington, United States, 98105

United States, Wisconsin

Childrens Hospital of Wisconsin (Medical College of Wisconsin)

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Matthew Larson Foundation

Investigators

• Study Chair: Kenneth Cohen, MD; Johns Hopkins University

More Information

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02212574 History of Changes
• Other Study ID Numbers: J1403; NA_00091840 ( Other Identifier: JHMIRB )
• First Posted: August 8, 2014
• Last Update Posted: January 17, 2019
• Last Verified: January 2019

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

Wnt; Medulloblastoma; Chemotherapy

Additional relevant MeSH terms:

Medulloblastoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Cisplatin; Cyclophosphamide; Vincristine; Lomustine; Mesna; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents