Radiation Therapy and Combination Chemotherapy in Treating Young Patients With Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Ependymoma - Full Text View

Study Description

Brief Summary:

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy in different ways and giving it together with more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which radiation therapy and combination chemotherapy regimen is more effective in treating medulloblastoma, supratentorial primitive neuroectodermal tumor (PNET), or ependymoma.

PURPOSE: This clinical trial is studying six different radiation therapy and combination chemotherapy regimens to compare how well they work in treating young patients with medulloblastoma, PNET, or ependymoma.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors	Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide phosphate Drug: high-dose chemotherapy Drug: lomustine Drug: methotrexate Drug: thiotepa Drug: vincristine sulfate Radiation: radiation therapy	Not Applicable

Detailed Description:

OBJECTIVES:

Compare prognosis, using adapted risk stratification and quality control of diagnostic assessments and therapy, in pediatric patients with intracranial medulloblastoma, supratentorial primitive neuroectodermal tumor (PNET), or ependymoma treated with intensified chemotherapy and radiotherapy.
Determine the effect of omission of radiotherapy, in terms of long-term sequelae, in young children with medulloblastoma and by hyperfractionation and reduction of radiotherapy in older children with medulloblastoma.
Compare hyperfractionated radiotherapy with reduced-dose radiotherapy in older children with stage M0 medulloblastoma.

OUTLINE: This is a multi-protocol study. Patients are enrolled on 1 of 6 treatment protocols according to diagnosis and age at diagnosis.

Protocol HIT-2000-AB4 (≥ 4 years old at diagnosis with nonmetastatic medulloblastoma)(phase III randomized controlled multicenter study): Patients are randomized to undergo hyperfractionated radiotherapy or conventional reduced-dose radiotherapy, followed by vincristine, lomustine, and cisplatin.
Protocol HIT-2000-BIS4 (< 4 years old at diagnosis with nonmetastatic medulloblastoma): Patients receive 5 courses of cyclophosphamide, vincristine, methotrexate, carboplatin, etoposide phosphate, and intrathecal methotrexate. Patients with residual tumors after 3 courses undergo conventionally fractionated reduced-dose radiotherapy.
Protocol MET-HIT-2000-AB4 (≥ 4 years old at diagnosis with metastatic medulloblastoma or supratentorial PNET): Patients receive combination chemotherapy as in HIT-2000-BIS4 for 2 courses. Patients then undergo hyperfractionated radiotherapy and receive combination chemotherapy as in HIT-2000-AB4. Patients with good response to combination chemotherapy (as in HIT-2000-BIS4) also receive high-dose chemotherapy.
Protocol MET-HIT-2000-BIS4 (< 4 years old at diagnosis with metastatic medulloblastoma or supratentorial PNET): Patients receive 2-4 courses of carboplatin IV and etoposide phosphate IV continuously over 96 hours. Patients with partial or complete response also receive high-dose carboplatin, etoposide phosphate, cyclophosphamide, and thiotepa. Patients with residual tumor undergo conventional fractionated, reduced-dose radiotherapy.
Protocol E-HIT-2000-AB4 (≥ 4 years old at diagnosis with intracranial ependymoma): Patients undergo local hyperfractionated radiotherapy. If histological grading shows WHO grade III tumor, patients also receive 5 courses of vincristine, cyclophosphamide, carboplatin, and etoposide phosphate.
Protocol E-HIT-2000-BIS4 (< 4 years old at diagnosis with intracranial ependymoma): Patients receive 5 courses of cyclophosphamide, vincristine, methotrexate IV, carboplatin, and etoposide phosphate and then undergo conventional fractionated local radiotherapy.

PROJECTED ACCRUAL: A total of 567 patients will be accrued for this study.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	567 participants
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Multicenter Therapy Optimizing Study for Treatment of Children and Adolescents With Intracranial Medulloblastoma / PNET and Ependymoma
Study Start Date :	January 2001
Actual Primary Completion Date :	December 2013

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Medulloblastoma Ependymoma Neuroepithelioma Medulloblastoma, Childhood Supratentorial Primitive Neuroectodermal Tumor Childhood Supratentorial Embryonal Tumor, Not Otherwise Specified Glioma

U.S. FDA Resources

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:	up to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of 1 of the following:
- Medulloblastoma
- Supratentorial primitive neuroectodermal tumor (PNET)
- Ependymoma
Intracranial tumor
- No brain stem tumors
No recurrent or relapsed tumors

PATIENT CHARACTERISTICS:

Not specified

PRIOR CONCURRENT THERAPY:

Not specified

Contacts and Locations

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): NCT00303810

Locations

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Germany
University Medical Center Hamburg - Eppendorf
Hamburg, Germany, D-20246

Sponsors and Collaborators

Universitätsklinikum Hamburg-Eppendorf

Investigators

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Study Chair:	Stefan Rutkowski, MD	University Med. Center Hamburg, Dpt. of Pediatric Hematology and Oncology
OverallOfficial:	Frank Deinlein, MD	Universitaets - Kinderklinik Wuerzburg

More Information

Publications of Results:

von Bueren AO, von Hoff K, Pietsch T, Gerber NU, Warmuth-Metz M, Deinlein F, Zwiener I, Faldum A, Fleischhack G, Benesch M, Krauss J, Kuehl J, Kortmann RD, Rutkowski S. Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology. Neuro Oncol. 2011 Jun;13(6):669-79. doi: 10.1093/neuonc/nor025.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

von Bueren AO, Kortmann RD, von Hoff K, Friedrich C, Mynarek M, Müller K, Goschzik T, Zur Mühlen A, Gerber N, Warmuth-Metz M, Soerensen N, Deinlein F, Benesch M, Zwiener I, Kwiecien R, Faldum A, Bode U, Fleischhack G, Hovestadt V, Kool M, Jones D, Northcott P, Kuehl J, Pfister S, Pietsch T, Rutkowski S. Treatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters. J Clin Oncol. 2016 Dec;34(34):4151-4160. Epub 2016 Oct 31.

Pompe RS, von Bueren AO, Mynarek M, von Hoff K, Friedrich C, Kwiecien R, Treulieb W, Lindow C, Deinlein F, Fleischhack G, Kuehl J, Rutkowski S. Intraventricular methotrexate as part of primary therapy for children with infant and/or metastatic medulloblastoma: Feasibility, acute toxicity and evidence for efficacy. Eur J Cancer. 2015 Nov;51(17):2634-42. doi: 10.1016/j.ejca.2015.08.009. Epub 2015 Sep 4.

von Bueren AO, Friedrich C, von Hoff K, Kwiecien R, Müller K, Pietsch T, Warmuth-Metz M, Hau P, Benesch M, Kuehl J, Kortmann RD, Rutkowski S. Metastatic medulloblastoma in adults: outcome of patients treated according to the HIT2000 protocol. Eur J Cancer. 2015 Nov;51(16):2434-43. doi: 10.1016/j.ejca.2015.06.124. Epub 2015 Aug 5.

Gerber NU, von Hoff K, Resch A, Ottensmeier H, Kwiecien R, Faldum A, Matuschek C, Hornung D, Bremer M, Benesch M, Pietsch T, Warmuth-Metz M, Kuehl J, Rutkowski S, Kortmann RD. Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy. Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):863-71. doi: 10.1016/j.ijrobp.2014.04.017.

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ClinicalTrials.gov Identifier:	NCT00303810
Other Study ID Numbers:	CDR0000455572 GPOH-HIT-2000 EU-205105
First Posted:	March 17, 2006 Key Record Dates
Last Update Posted:	January 28, 2014
Last Verified:	July 2009

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:


childhood infratentorial ependymoma childhood supratentorial ependymoma untreated childhood medulloblastoma newly diagnosed childhood ependymoma untreated childhood supratentorial primitive neuroectodermal tumor

Additional relevant MeSH terms:

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Ependymoma Nervous System Neoplasms Central Nervous System Neoplasms Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Glioma Neoplasms, Neuroepithelial Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases	Cyclophosphamide Thiotepa Lomustine Carboplatin Methotrexate Etoposide Vincristine Etoposide phosphate Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action