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Trial record 2 of 7 for:    "Medulloblastoma" | "Mesna"

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

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ClinicalTrials.gov Identifier: NCT00031590
Recruitment Status : Terminated (The study was terminated prematurely due to slow accrual.)
First Posted : January 27, 2003
Results First Posted : April 25, 2019
Last Update Posted : April 25, 2019
Sponsor:
Collaborators:
Stanford University
Emory University
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

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.

Condition or disease Intervention/treatment Phase
Brain Tumors Central Nervous System Tumors Medulloblastoma Drug: Cisplatin Drug: Cyclophosphamide Drug: Etoposide Drug: Lomustine Drug: Vincristine Radiation: Craniospinal Radiation Phase 2

Detailed Description:

OBJECTIVES:

  • By giving reduced dose craniospinal radiation followed by nine cycles of maintenance chemotherapy comprised of alternating cycles of lomustine, cisplatin, and vincristine alternating with cyclophosphamide and etoposide, we will reduce the late effects of higher dose radiation in children while maintaining the therapeutic efficacy (86% 3-year relapse-free survival) of current standard therapy
  • To evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of cognitive, endocrinologic, and auditory function, in these patients.

OUTLINE: This is a multi center study of reduced dose craniospinal radiotherapy and chemotherapy in patients ages 3 - 30 years with newly diagnosed average risk medulloblastoma.

  • Induction chemoradiotherapy: Beginning within 28 days after complete surgical resection, patients undergo radiotherapy to the craniospinal axis (1800 centigray (cGy)) followed by conformal radiotherapy to the tumor bed (5400 cGy). Patients receive vincristine weekly for 6 weeks.
  • Maintenance chemotherapy: Beginning 4 weeks after the completion of craniospinal radiation therapy, patients receive two 6-week courses of regimen A as outlined below alternating with one 6-week course of regimen B for a total of 9 courses (AABAABAAB).

    • Regimen A: Patients receive oral lomustine and cisplatin on day 0 and vincristine on days 0, 7, and 14.
    • Regimen B: Patients receive cyclophosphamide on days 0 and 1 and etoposide intravenous (IV) on days 0 and 1, followed by oral etoposide on days 14-34.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter with surveillance neuroimaging using Magnetic Resonance Imaging Scan (MRI scan) and clinical examination.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study Of Reduced Dose Craniospinal Radiotherapy (1800 cGy) And Chemotherapy In Children With Newly-Diagnosed Standard-Risk Posterior Fossa Primitive Neuro-ectodermal Tumor (PNET/Medulloblastoma)
Study Start Date : April 2001
Actual Primary Completion Date : May 2011
Actual Study Completion Date : May 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Study Treatment
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
Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only).
Other Names:
  • CDDP
  • Platinum

Drug: Cyclophosphamide
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).
Other Name: Cytoxan

Drug: Etoposide
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).
Other Name: VP-16

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

Drug: Vincristine
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).
Other Name: Oncovin

Radiation: Craniospinal 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).
Other Name: Radiation




Primary Outcome Measures :
  1. Evaluate Rate of Late Neurotoxic Effects [ Time Frame: 3 years ]
    Evaluate the late neurotoxic effects of low dose craniospinal radiation, including neurocognitive decline as measured by serial neurocognitive testing.


Secondary Outcome Measures :
  1. Long Term Survival [ Time Frame: 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. ]

    Survival Endpoints:

    Event free survival and overall survival were assessed at 5 years from time of study enrollment




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Ages Eligible for Study:   3 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed medulloblastoma
  2. Standard-risk disease
  3. 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
  4. Must begin radiotherapy on study within 28 days after surgery

Exclusion Criteria:

  1. Prior radiotherapy and anti-tumor chemotherapy other than corticosteroids are not allowed.
  2. Pregnant females will not be eligible
  3. Patients must begin radiotherapy on protocol within 28 days of completion of surgery. Exceptions need to be approved by the Principal Investigator.
  4. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00031590


Locations
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United States, California
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Sponsors and Collaborators
Children's Hospital of Philadelphia
Stanford University
Emory University
Investigators
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Principal Investigator: Peter C. Phillips, MD Children's Hospital of Philadelphia

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Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00031590     History of Changes
Other Study ID Numbers: 00-002301
CHP-693 ( Other Identifier: Children's Hospital of Philadelphia )
First Posted: January 27, 2003    Key Record Dates
Results First Posted: April 25, 2019
Last Update Posted: April 25, 2019
Last Verified: April 2019

Keywords provided by Children's Hospital of Philadelphia:
average risk medulloblastoma
craniospinal radiotherapy
newly diagnosed

Additional relevant MeSH terms:
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Medulloblastoma
Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Site
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
Cisplatin
Cyclophosphamide
Etoposide
Etoposide phosphate
Vincristine
Lomustine
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