Neoplasms

Nervous System Diseases

All Conditions

Rare Diseases

Brain Neoplasms

Central Nervous System Neoplasms

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

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

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Etoposide

Cyclophosphamide

Vincristine

Cisplatin

Lomustine

Etoposide phosphate

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

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).

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

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).

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).

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

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).

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).

Craniospinal Radiation

Peter C. Phillips, MD

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.

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.

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

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)

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

Survival Endpoints:

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

Stanford University

Emory University

Children's Hospital of Philadelphia

Adverse events were recorded in the following categories: auditory toxicity, renal toxicity, and endocrinologic toxicity

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) which will be given in the following order (total of 54 weeks):1st-Regimen A, 2nd-Regimen A, 3rd-Regimen B, 4th-Regimen A, 5th-Regimen A, 6th-Regimen B, 7th-Regimen A, 8th-Regimen A, 9th-Regimen B Cisplatin: Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only). Cyclophosphamide: Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6

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) which will be given in the following order (total of 54 weeks):1st-Regimen A, 2nd-Regimen A, 3rd-Regimen B, 4th-Regimen A, 5th-Regimen A, 6th-Regimen B, 7th-Regimen A, 8th-Regimen A, 9th-Regimen B. Cisplatin: Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only). Cyclophosphamide: Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6

Age, Categorical

Sex: Female, Male

White

African american

Asian

Hispanic

Other

Race/Ethnicity, Customized

United States

Region of Enrollment

Peter Phillips

All subjects will undergo surgical resection and routine staging (MRI spine and LP for CSF cytology). Subjects aged 3-30 yrs with M0 disease are eligible. Treatment must begin within 28 days of surgery. Reduced dose craniospinal irradiation (CSI) (1800 centiGray (cGy) CSI + 3780 cGy tumor bed) will last for 6 weeks with concurrent, weekly vincristine. 4 weeks after radiation therapy is completed, all subjects will begin 9 cycles of maintenance chemotherapy: Regimen A (CCNU, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide). Cycles will be given as AABAABAAB

Regimen A:

Cisplatin: 70mg/m2/dose x 1 dose on day 0 Vincristine: 1.5 mg/m2/dose on days 0, 7, 14 CCNU: 75 mg/m2/dose x 1 dose on day 0

Regimen B:

Cyclophosphamide: 1g/m2/dose on days 0 and 1 Etoposide: 150 mg/m2/dose (IV) on days 0 and 1 Etoposide: 50 mg/m2/day PO on days 14-34 (21 days total)

The primary endpoint was not met due to lack of evaluable data from non-compliance with neurocognitive testing. Baseline neurocognitive testing was performed on 5 of 28 (18%) of study subjects. Of those 5 subjects with baseline testing, only 1 completed follow up neurocognitive testing at the protocol specified time points.

Evaluate Rate of Late Neurotoxic Effects

5 year Overall Survival (OS)

5 year Event Free Survival (EFS)

All subjects will undergo surgical resection and routine staging (Magnetic Resonance Imagine (MRI) spine and Lumbar Puncture (LP) for cerebrospinal fluid (CSF) cytology). Subjects aged 3-30 yrs with M0 disease are eligible. Treatment must begin within 28 days of surgery. Reduced dose craniospinal RT (1800 cGy CSI + 3780 cGy tumor bed) will last for 6 weeks with concurrent, weekly vincristine. 4 weeks after radiation therapy is completed, all subjects will begin 9 cycles of maintenance chemotherapy: Regimen A (Lomustine (CCNU), Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide). Cycles will be given as AABAABAAB

Regimen A:

Cisplatin: 70mg/m2/dose x 1 dose on day 0 Vincristine: 1.5 mg/m2/dose on days 0, 7, 14 CCNU: 75 mg/m2/dose x 1 dose on day 0

Regimen B:

Cyclophosphamide: 1g/m2/dose on days 0 and 1 Etoposide: 150 mg/m2/dose intravenous (IV) on days 0 and 1 Etoposide: 50 mg/m2/day oral (PO) on days 14-34 (21 days total)

All subjects who received radiation and started chemotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma	NCT00031590	Brain Tumors Central Nervous... Medulloblastoma	Cisplatin Cyclophosphamid... Etoposide Lomustine Vincristine Craniospinal Ra...	3 Years - 30 Years	Children's Hospital of Philadelphia
Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma	NCT00031590	Brain Tumors Central Nervous... Medulloblastoma	Cisplatin Cyclophosphamid... Etoposide Lomustine Vincristine Craniospinal Ra...	3 Years - 30 Years	Children's Hospital of Philadelphia

Spots Global Cancer Trial Database for average risk medulloblastoma