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 (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02212574
• Collaborator: Matthew Larson Foundation (Other)
• Enrollment: 6
• Locations: 16
• Arm: 1
• Actual Duration (Months): 19.2
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

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; Drug: Vincristine	Early Phase 1

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
• Actual Enrollment: 6 participants
• Allocation: N/A
• 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: Apr 4, 2017
• Actual Primary Completion Date: Nov 9, 2018
• Actual Study Completion Date: Nov 9, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [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; the number of participants who with progression free survival.

Secondary Outcome Measures

1. Patterns of Failure [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

Criteria

• Ages Eligible for Study: 3 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Phoenix Childrens Hospital Hematology/Oncology	Phoenix	Arizona	United States	85016-7710
2	Children's Hospital Colorado Center for Cancer & Blood Disorders	Aurora	Colorado	United States	80045
3	M D Anderson Cancer Center-Orlando Pediatric Hematology/Oncology	Orlando	Florida	United States	32806
4	All Children's Hospital Pediatric Hematology/Oncology	Saint Petersburg	Florida	United States	33701
5	Children's Healthcare of Atlanta- Egleston Pediatric Neuro-Oncology	Atlanta	Georgia	United States	30322
6	Ann and Robert H Lurie Children's Hospital of Chicago Hematology/Oncology	Chicago	Illinois	United States	60611
7	Johns Hopkins University	Baltimore	Maryland	United States	21287
8	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
9	Washington University School of Medicine Pediatric Hematology/Oncology	Saint Louis	Missouri	United States	63110
10	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
11	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
12	Duke University Medical Center	Durham	North Carolina	United States	27705
13	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
14	Oregon Health and Science University Pediatric Hematology/Oncology	Portland	Oregon	United States	97239-3098
15	Seattle Children's Hospital Hematology/Oncology	Seattle	Washington	United States	98105
16	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

Study Documents (Full-Text)

• Study Protocol - Sep 12, 2016
• Statistical Analysis Plan - Sep 12, 2016
• Informed Consent Form - May 11, 2016

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02212574
• Other Study ID Numbers: J1403; NA_00091840
• First Posted: Aug 8, 2014
• Last Update Posted: Nov 5, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Wnt; Medulloblastoma; Chemotherapy
• Additional relevant MeSH terms: Medulloblastoma; Cyclophosphamide; Lomustine; Vincristine

Study Results

Participant Flow

Arm/Group Title	Chemotherapy
Arm/Group Description	Chemotherapy Cycle A Lomustine (CCNU) given by mouth on Day 1. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin given directly into a vein over 8 hours on Day 1. Cycle lasts 42 days. Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 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 & 6 hours. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.Cycle lasts 28 days Lomustine: Chemotherapy Cycle A Lomustine (CCNU) given by mouth on Day Vincristine: Chemotherapy Cycle A Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin: Chemotherapy Cycle A Cisplatin given directly into a vein over 8 hours on Day 1. Cyclophosphamide: Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 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 & 6 hours. Vincristine: Chemotherapy Cycle B Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Chemotherapy
Arm/Group Description	Chemo Cycle A Lomustine (CCNU) given by mouth on Day 1. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin given directly into a vein over 8 hours on Day 1. Cycle lasts 42 days. Chemo Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 and 2. MESNA, a drug to protect the bladder from effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide, repeated at 3 and 6 hours. Vincristine 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 & 8. Cycle lasts 28 days Lomustine: Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1. Vincristine: Chemo Cycle A Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin: Chemo Cycle A Cisplatin is given directly into a vein over 8 hours on Day 1. Cyclophosphamide: Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 2. Mesna: Chemo Cycle B MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide, repeated at 3 & 6 hours. Vincristine: Chemo Cycle B Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.
Overall Participants	6
Age (Count of Participants)
<=18 years	6 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	7
Sex: Female, Male (Count of Participants)
Female	5 83.3%
Male	1 16.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%
Not Hispanic or Latino	5 83.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 50%
White	3 50%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	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.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

This outcome was not assessed because some patients had a relapse and study was abruptly terminated.

Arm/Group Title	All Patients
Arm/Group Description	Chemotherapy Cycle A Lomustine (CCNU) given by mouth on Day 1. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin given directly into a vein over 8 hours on Day 1. Cycle lasts 42 days. Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 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 & 6 hours. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.Cycle lasts 28 days Lomustine: Chemotherapy Cycle A Lomustine (CCNU) given by mouth on Day Vincristine: Chemotherapy Cycle A Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin: Chemotherapy Cycle A Cisplatin given directly into a vein over 8 hours on Day 1. Cyclophosphamide: Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 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 & 6 hours. Vincristine: Chemotherapy Cycle B Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.
Measure Participants	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

This outcome was not assessed because some patients had a relapse and study was abruptly terminated.

Arm/Group Title	Chemotherapy
Arm/Group Description	Chemotherapy Cycle A Lomustine (CCNU) given by mouth on Day 1. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin given directly into a vein over 8 hours on Day 1. Cycle lasts 42 days. Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 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 & 6 hours. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.Cycle lasts 28 days Lomustine: Chemotherapy Cycle A Lomustine (CCNU) given by mouth on Day Vincristine: Chemotherapy Cycle A Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin: Chemotherapy Cycle A Cisplatin given directly into a vein over 8 hours on Day 1. Cyclophosphamide: Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 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 & 6 hours. Vincristine: Chemotherapy Cycle B Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	Adverse events were not collected for standard of care chemotherapy.
Arm/Group Title	All Participants
Arm/Group Description	Chemotherapy Cycle A Lomustine (CCNU) given by mouth on Day 1. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin given directly into a vein over 8 hours on Day 1. Cycle lasts 42 days. Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 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 & 6 hours. Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.Cycle lasts 28 days Lomustine: Chemotherapy Cycle A Lomustine (CCNU) given by mouth on Day Vincristine: Chemotherapy Cycle A Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, & 15. Cisplatin: Chemotherapy Cycle A Cisplatin given directly into a vein over 8 hours on Day 1. Cyclophosphamide: Chemotherapy Cycle B Cyclophosphamide given into a vein over 1 hour on Days 1 & 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 & 6 hours. Vincristine: Chemotherapy Cycle B Vincristine given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 & 8.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

Two of the participants relapsed not long into the study and the Data and Safety Management Committee (DSMC) recommended early closure of the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.