Combination Chemotherapy in Treating Children With Astrocytomas and Primitive Neuroectodermal Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00002463
First received: November 1, 1999
Last updated: February 14, 2013
Last verified: February 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of methotrexate, mechlorethamine, vincristine, procarbazine, and prednisone in treating children with astrocytomas or primitive neuroectodermal tumors.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: MOPP Regimen
Drug: Leucovorin Calcium
Drug: Mechlorethamine Hydrochloride
Drug: Methotrexate
Drug: Prednisone
Drug: Procarbazine Hydrochloride
Drug: Vincristine Sulfate
Procedure: Conventional Surgery
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Methotrexate, Mechlorethamine, Vincristine, Prednisone, and Procarbazine (MMOPP) as Primary Therapy in Infants or Young Children With Primitive Neuroectodermal Tumors or High-Grade Astrocytoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Patient with Overall Response [ Time Frame: Every 31 days ] [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: February 1989
Study Completion Date: January 2008
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination Chemotherapy
Methotrexate, Mechlorethamine, Vincristine, Prednisone, and Procarbazine
Drug: MOPP Regimen
Methotrexate, Mechlorethamine, Vincristine, Prednisone, and Procarbazine (MMOPP)
Drug: Leucovorin Calcium Drug: Mechlorethamine Hydrochloride Drug: Methotrexate Drug: Prednisone Drug: Procarbazine Hydrochloride Drug: Vincristine Sulfate Procedure: Conventional Surgery

Detailed Description:

OBJECTIVES: I. Determine the efficacy of high-dose methotrexate (HMTX) in combination with mechlorethamine, vincristine, prednisone, and procarbazine (MOPP) in infants or young children with primitive neuroectodermal tumors (PNET) (including medulloblastoma, anaplastic ependymoma, ependymoblastoma, or pineoblastoma) or high-grade astrocytoma. II. Determine whether the addition of HMTX to MOPP (MMOPP) improves the continuous complete response rate of MOPP alone and eliminates the need for salvage with radiotherapy in these patients. III. Determine the ability of MMOPP to provide neuroaxis prophylaxis or to treat spinal metastasis without radiotherapy in infants or young children with PNET. IV. Determine the toxicity of this regimen in terms of neurologic and neuropsychologic sequelae, growth, and development in these patients. V. Correlate the efficacy of this regimen with the histopathologic diagnosis of these patients. VI. Determine the optimum method for radiographic evaluation of spinal cord disease in patients with PNET. VII. Determine the utility of sequential spinal cord radiography as a means of monitoring PNET in these patients.

OUTLINE: Patients undergo maximum tumor debulking. Patients who have undergone incomplete resection proceed to induction. Patients with a primary diagnosis of primitive neuroectodermal and pineal tumors or glioblastoma multiforme who have undergone total resection proceed to induction. Induction: Patients receive high dose methotrexate (HMTX) IV over 6 hours on day 1. Beginning 3 hours after completion of HMTX infusion, leucovorin calcium (CF) is administered IV over 30 minutes every 3 hours for 9 doses. Beginning 3 hours after completion of the last CF infusion, oral CF is administered every 6 hours for 8 doses. Patients receive a second HMTX infusion beginning 1 week after completion of the first HMTX infusion. Beginning 1 week after completion of the second HMTX infusion, patients receive mechlorethamine IV and vincristine IV on days 1 and 8, oral procarbazine and oral prednisone on days 1-10, and tapered doses of prednisone on days 11-13 (MOPP). Maintenance: Beginning 4 weeks after initiating the first course of MOPP, patients receive HMTX on day 1 and MOPP beginning on day 4. Treatment continues every 31 days in the absence of disease progression or unacceptable toxicity. After 1 year or 14 doses of HMTX, whichever occurs first, HMTX is discontinued and treatment with MOPP alone continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Treatment is discontinued after 2 years if the patient is in continuous complete remission.

PROJECTED ACCRUAL: A total of 5-25 patients will be accrued for this study within 24-30 months.

  Eligibility

Ages Eligible for Study:   up to 3 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically proven previously untreated (except surgically) primitive neuroectodermal tumors (including medulloblastoma, anaplastic ependymoma, ependymoblastoma, or pineoblastoma) or high-grade astrocytomas Low-grade astrocytomas or optic tract tumors that are incompletely resected and have a progressive course not amenable to further surgery may also be allowed Evaluable disease by MRI, CT scan, or CT myelography

PATIENT CHARACTERISTICS: Age: Under 4 years Performance status: Not specified Life expectancy: At least 12 weeks Hematopoietic: Absolute granulocyte count greater than 1,500/mm3 WBC greater than 4,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL SGPT less than 90 IU/dL Renal: Creatinine clearance greater than 80 mL/min

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: No prior mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) No prior high-dose methotrexate No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No concurrent radiotherapy Surgery: See Disease Characteristics Other: Recovered from acute toxic effects of any prior therapy Must be on a tyramine-free diet during procarbazine administration

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002463

Locations
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Joann Ater, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Ater J, Worth L, Bruner J, et al.: Young children treated with MOPP or methotrexate-MOP for medulloblastoma: identification of a subset of patients with good prognosis. [Abstract] Proceedings of the American Society of Clinical Oncology 14: A-1397, 1995.
Ater JL, van Eys J, Yung WK, et al.: Response to methotrexate, mechlorethamine, vincristine, procarbazine, and prednizone (MMOPP) for brain tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 10: A-370, 125, 1991.

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00002463     History of Changes
Other Study ID Numbers: P88-006, P30CA016672, MDA-P-88006, NCI-V89-0125, CDR0000075917
Study First Received: November 1, 1999
Last Updated: February 14, 2013
Health Authority: United States: Federal Government

Keywords provided by M.D. Anderson Cancer Center:
childhood infratentorial ependymoma
childhood low-grade cerebral astrocytoma
childhood low-grade cerebellar astrocytoma
childhood supratentorial ependymoma
childhood high-grade cerebral astrocytoma
untreated childhood supratentorial primitive neuroectodermal tumor
untreated childhood cerebellar astrocytoma
untreated childhood medulloblastoma
untreated childhood visual pathway and hypothalamic glioma
newly diagnosed childhood ependymoma

Additional relevant MeSH terms:
Neoplasms
Astrocytoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Glioma
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Levoleucovorin
Vincristine
Methotrexate
Prednisone
Mechlorethamine
Procarbazine
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on September 30, 2014