Clinical Trial: Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
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 Phas
Brief 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.
Detailed Summary:
PRIMARY OBJECTIVES:
I. 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:
I. 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.
V. 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 w
Sponsor: Children's Oncology Group
Current Primary Outcome: Event-free survival (EFS) [ Time Frame: Time from study entry to disease progression, disease recurrence, death from any cause, or occurrence of a second malignant neoplasm, or to the date of last follow-up for patients without events Timeframe: Assessed at 3 years ]
Original Primary Outcome:
Current Secondary Outcome:
- Time to death from any cause / overall survival (OS) [ Time Frame: Time from study entry to death from any cause or to the date of last follow-up for surviving patients Timeframe: Assessed at 3 years ]Used to compute overall survival (OS). Three-year OS rates will be reported. Comparisons of OS for each of the two radiation therapy questions (IFRT vs. PFRT and LDCSI vs. SDCSI) will be based on one-sided log rank tests. The analysis of CSI dose will be stratified on the PF volume and the analysis of PF volume will be stratified by age group (3-7 years vs. 8-21 years) and CSI group. Intent to treat analysis will be used. All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included in the two survival comparisons.
- Local posterior fossa (LPF) failure rate [ Time Frame: Up to 3 years ]LPF failure is defined as tumor recurrence or progression within the tumor bed; i.e., within clinical target volume CTVboost for patients randomized to tumor-bed-only (involved field) boost (or within a theoretical CTVboost for patients randomized to standard PF radiation therapy). Recurrent tumors that straddle the boundary of CTVboost will be classified as LPF if more than 50% of the tumor volume is within CTVboost All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included. Three-year LPF failure rates will be reported separately for IFRT vs. PFRT patients.
- Non-local posterior fossa (NLPF) failure rate [ Time Frame: Up to 3 years ]
NLPF failure is defined as tumor outside CTVboost, but within CTVPF. Recurrent tumors that straddle the boundary of CTVboost will be classified as non-local posterior fossa (NLPF) if more than 50% of the tumor volume is outside of CTVboost. Recurrent tumors that straddle the boundary of CTVPF will be classified as LPF if more than 50% of the tumor volume is within CTVPF.
All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included. Three-year NLPF failure rates will be reported separately for IFRT vs. PFRT patients.
- Non-posterior fossa (NPF) failure rate [ Time Frame: Up to 3 years ]
NPF is defined as tumor recurrence within the neuroaxis but outside of CTVPF. Recurrent tumors that straddle the boundary of CTVPF will be classified as NPF if more than 50% of the tumor volume is outside of CTVPF.
All randomized eligible and evaluable patients (patients without disease dissemination or excess residual disease by central review and patients without anaplastic histology) will be included. Three-year NPF failure rates will be reported separately for IFRT vs. PFRT patients.
- Post-treatment endocrine function (growth hormone (GH) and thyroid stimulating hormone (TSH)) as measured by laboratory assessment) . [ Time Frame: Up to 3 years ]Growth hormone stimulation tests were performed and noted as normal or abnormal at baseline and after completion of therapy/follow-up. Proportions of patients with abnormal results after completion of therapy will be calculated and reported separately for LDCSI vs. SDCSI patients. Mean post-treatment TSH levels will be reported by CSI group. Eligible and evaluable patients 3-7 years of age will be used.
- Post-treatment grade 3+ hearing loss as measured by CTCAE v4 [ Time Frame: Up to 1 year after the end of treatment ]Proportions of patients with grade 3+ hearing loss after the completion of therapy will be calculated and reported separately for LDCSI vs. SDCSI patients. Eligible and evaluable patients 3-7 years of age will be used.
- Post-treatment neurocognitive function as measured by the estimated full-scale IQ (FSIQ) and also the metacognition index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) [ Time Frame: Up to 6 years post-diagnosis ]Average scores for FSIQ and MI will be reported at each of the 3 neurocognitive assessment time points by LDCSI vs. SDCSI groups. All eligible and evaluable patients 3-7 years of age will be used.
- Incidence of grade 3+ hearing loss at 1-year post treatment as assessed by CTCAE Version 4 [ Time Frame: 1 year after end of treatment ]Incidence rates will be reported separately for eligible and evaluable IFRT and PFRT patients.
- Incidence of endocrine dysfunction as measured by growth hormone stimulation test at the completion of therapy. [ Time Frame: After completion of therapy, an average of 2 years ]Incidence rates of abnormal growth hormone stimulation tests at the after completion of therapy assessment will be reported separately for eligible and evaluable IFRT
Original Secondary Outcome:
Information By: Children's Oncology Group
Dates:
Date Received: June 14, 2004
Date Started: April 2004
Date Completion:
Last Updated: February 9, 2017
Last Verified: February 2017
