Summary

Eligibility
for people ages 3-21 (full criteria)
Location
at Oakland, California and other locations
Dates
study started

Description

Summary

This randomized phase III trial is studying how well standard-dose radiation therapy works compared to reduced-dose radiation therapy in children 3-7 years of age AND how well standard volume boost radiation therapy works compared to smaller volume boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy is more effective than reduced-dose radiation therapy when given together with chemotherapy after surgery in treating young patients with medulloblastoma.

Official Title

A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial

Details

PRIMARY OBJECTIVES:

  1. Compare event-free survival (EFS) of pediatric patients (3 to 7 years of age) with newly diagnosed standard-risk medulloblastoma treated with standard-dose versus (vs.) reduced-dose craniospinal radiotherapy (SDCSI vs. LDCSI).

II. Compare EFS of patients (3-21 years of age) treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with this chemotherapy regimen.

SECONDARY OBJECTIVES:

  1. Compare overall survival (OS) of pediatric patients (3-7 years of age) with newly diagnosed standard-risk medulloblastoma treated with SDCSI vs. LDCSI.

II. Compare OS of patients (3-21 years of age) with newly diagnosed standard-risk medulloblastoma treated with PFRT vs. IFRT.

III. To evaluate patterns of failure in patients treated with an irradiation boost volume smaller than conventional posterior fossa volumes.

IV. To reduce the cognitive, auditory, and endocrinologic effects of treatment of average-risk medulloblastoma by reducing the dose of craniospinal irradiation therapy.

  1. To determine if the audiologic and endocrinologic toxicity will be reduced with the use of limited tumor boost volume irradiation compared to patients treated with conventional target volumes of radiation.

VI. Develop an optimal gene expression medulloblastoma outcome predictor, validated prospectively in a multi-institution randomized clinical trial.

VII. To improve compliance with long-term quality of life (QoL) and functional status data submission by educating institutional nurses to administer and submit for analysis a battery of four instruments (Behavior Assessment System for Children- 2nd Edition (BASC-2), Adaptive Behavior Assessment System - 2nd Edition (ABAS-II), Behavior Rating Inventory of Executive Function (BRIEF) and PedsQLTM 4.0).

OUTLINE: Patients 3-7 years of age are randomized to 1 of 4 arms (Arm I-IV). Patients 8-21 years of age are randomized to 1 of 2 arms (Arm V or VI).

Within 31 days after definitive surgery, all patients begin therapy. Patients undergo radiation therapy with doses according to their Arm randomization on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). All patients receive vincristine intravenously (IV) over 1 minute (or infusion via minibag as per institutional policy) on days 8, 15, 22, 29, 36, and 43 (weeks 1-6).

ARM I: Patients 3-7 years of age undergo lowered dose craniospinal irradiation (LDCSI) with involved-field radiation therapy (IFRT) boost.

ARM II: Patients 3-7 years of age undergo LDCSI with whole posterior fossa radiation therapy (PFRT) boost.

ARM III: Patients 3-7 years of age undergo standard dose craniospinal irradiation (SDCSI) with IFRT boost.

ARM IV: Patients 3-7 years of age undergo SDCSI with PFRT boost.

ARM V: Patients 8-21 years of age undergo SDCSI with IFRT boost.

ARM VI: Patients 8-21 years of age undergo SDCSI with PFRT boost.

MAINTENANCE CHEMOTHERAPY: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration.

REGIMEN A (courses 1, 2, 4, 5, 7, and 8): Patients receive lomustine orally and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49.

REGIMEN B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55.

Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Keywords

Untreated Childhood Medulloblastoma Medulloblastoma Cyclophosphamide Lomustine Cisplatin Vincristine Craniospinal Irradiation Involved-Field Radiation Therapy Laboratory Biomarker Analysis Quality-of-Life Assessment Radiation Therapy Vincristine Sulfate

Eligibility

For people ages 3-21

Inclusion Criteria:

  • Histologically confirmed medulloblastoma located in the posterior fossa
  • Standard-risk disease
  • Minimal volume, non-disseminated disease, defined by the following:
  • Residual tumor ≤ 1.5 cm2 confirmed by MRI with contrast imaging within 21 days after surgery

  • No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:
  • Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
  • Negative cytological examination of CSF after surgery, but before study enrollment
  • Brain stem involvement allowed
  • Performance status - Karnofsky 50-100% (> 16 years of age)
  • Performance status - Lansky 30-100% (≤ 16 years of age)
  • Absolute neutrophil count > 1,500/uL
  • Platelet count > 100,000/uL (transfusion independent)
  • Hemoglobin > 10 g/dL (transfusions allowed)
  • Bilirubin < 1.5 times upper limit of normal (ULN) for age
  • AST or ALT < 1.5 times ULN for age
  • Creatinine clearance OR radioisotope glomerular filtration rate >= 70 mL/min/1.73m2 or a serum creatinine based on age/gender as follows:

Age Maximum Serum Creatine (mg/dL)

  • 1month to < 6 months male: 0.4 female: 0.4
  • 6 months to <1 year male: 0.5 female: 0.5
  • 1 year to < 2 years male: 0.6 female: 0.6
  • 2 to < 6 years male: 0.8 female: 0.8
  • 6 to < 10 years male: 1 female: 1
  • 10 to < 13 years male: 1.2 female: 1.2
  • 13 to < 16 years male: 1.5 female: 1.4
  • >= 16 years male: 1.7 female: 1.4
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior chemotherapy
  • Prior corticosteroids allowed
  • No prior radiotherapy

Locations

  • Children's Hospital and Research Center at Oakland
    Oakland California 94609-1809 United States
  • Kaiser Permanente-Oakland
    Oakland California 94611 United States
  • Children's Hospital Central California
    Madera California 93636-8762 United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Children's Oncology Group
ID
NCT00085735
Phase
Phase 3
Study Type
Interventional
Last Updated