Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma

NCT00031590 | Terminated Phase 2 Results DMC

• 2 other identifiers: 00-002301CHP-693
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells, but also damages normal cells in the developing brains of children. Combining low-dose radiation therapy in combination with chemotherapy should be effective in treating medulloblastoma while avoiding the long-term side effects of giving higher dose radiation to children with newly diagnosed average risk medulloblastoma.

Conditions

Brain Tumors; Central Nervous System Tumors; Medulloblastoma

Keywords

average risk medulloblastoma; craniospinal radiotherapy; newly diagnosed

Outcome Measures

Primary Outcomes (1)

• Evaluate Rate of Late Neurotoxic Effects

  Evaluate the late neurotoxic effects of low dose craniospinal radiation, including neurocognitive decline as measured by serial neurocognitive testing.

  3 years

Secondary Outcomes (1)

• Long Term Survival

  Up to 5 years from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.

Study Arms (1)

Study Treatment

EXPERIMENTAL

All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide \[IV and oral\]) which will be given in the following order: AABAABAAB (total of 54 weeks).

Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Lomustine; Drug: Vincristine; Radiation: Craniospinal Radiation

Interventions

Cisplatin DRUG

Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only).

Also known as: CDDP, Platinum

Study Treatment

Cyclophosphamide DRUG

Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Administration of cyclophosphamide will always be preceded by prehydration and Mesna (Regimen B only).

Also known as: Cytoxan

Study Treatment

Etoposide DRUG

Given at a dose of 150mg/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Given orally at a dose of 50mg/m2 as a single daily dose for 21 days beginning on day 14 of a cycle (Regimen B only).

Also known as: VP-16

Study Treatment

Lomustine DRUG

Given at a dose of 75mg/m2 taken orally on days 0 of each 6-week cycle with vincristine and cisplatin (Regimen A only).

Also known as: CCNU

Study Treatment

Vincristine DRUG

Given at a dose of 1.5mg/m2 given by IV infusion once a week for the first six weeks of treatment during radiation therapy. During maintenance therapy, it will be given as an IV push on days 0, 7 and 14 of each 6-week cycle (Regimen A only).

Also known as: Oncovin

Study Treatment

Craniospinal Radiation RADIATION

Craniospinal radiation will begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with chemotherapy (vincristine).

Also known as: Radiation

Study Treatment

Eligibility Criteria

• Age: 3 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologically confirmed medulloblastoma
• Standard-risk disease
• No residual tumor greater than 1.5 cm\^2 after resection by postoperative MRI
• No tumor in the spinal or cerebral subarachnoid space by MRI
• No tumor in the subarachnoid space by Cerebrospinal fluid (CSF)
• No failure to perform staging studies (spine MRI and CSF cytology) preoperatively or postoperatively
• Must begin radiotherapy on study within 28 days after surgery

You may not qualify if:

• Prior radiotherapy and anti-tumor chemotherapy other than corticosteroids are not allowed.
• Pregnant females will not be eligible
• Patients must begin radiotherapy on protocol within 28 days of completion of surgery. Exceptions need to be approved by the Principal Investigator.
• Patients with the following will not be eligible:
• \> 1.5cm3 residual tumor following resection as indicated by post-operative MRI.
• tumor in spinal or cerebral subarachnoid space either by MRI of brain and spine
• tumor in subarachnoid space by CSF cytology
• failure to perform staging studies (spine MRI, CSF cytology) either pre- or post- operatively

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Stanford University: collaborator
• Emory University: collaborator

Study Sites (3)

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Related Publications (1)

• Minturn JE, Mochizuki AY, Partap S, Belasco JB, Lange BJ, Li Y, Phillips PC, Gibbs IC, Fisher PG, Fisher MJ, Janss AJ. A Pilot Study of Low-Dose Craniospinal Irradiation in Patients With Newly Diagnosed Average-Risk Medulloblastoma. Front Oncol. 2021 Sep 2;11:744739. doi: 10.3389/fonc.2021.744739. eCollection 2021.

  PMID: 34540703 DERIVED

MeSH Terms

Conditions

Brain Neoplasms; Central Nervous System Neoplasms; Medulloblastoma

Interventions

Cisplatin; Platinum; Cyclophosphamide; Etoposide; Lomustine; Vincristine; Radiation

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Physical Phenomena

Results Point of Contact

• Title: Peter Phillips
• Organization: Childrens Hospital of Philadelphia

phillipsp@email.chop.edu

215-590-1000

Study Officials

• Peter C. Phillips, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2002
• First Posted: January 27, 2003
• Study Start: April 1, 2001
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: April 25, 2019
• Results First Posted: April 25, 2019

Record last verified: 2019-04

Locations

US (3)