Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET
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| ClinicalTrials.gov Identifier: NCT00392327 |
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Recruitment Status :
Active, not recruiting
First Posted : October 26, 2006
Results First Posted : August 7, 2020
Last Update Posted : January 9, 2023
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Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
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Brief Summary:
This randomized phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Drugs used in chemotherapy, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Anaplastic Medulloblastoma Medulloblastoma | Drug: Carboplatin Drug: Cisplatin Drug: Cyclophosphamide Biological: Filgrastim Drug: Isotretinoin Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Radiation: Radiation Therapy Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 379 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients |
| Actual Study Start Date : | March 26, 2007 |
| Actual Primary Completion Date : | June 30, 2019 |
| Estimated Study Completion Date : | July 30, 2028 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days). Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. |
Drug: Cisplatin
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Radiation: Radiation Therapy Undergo radiation therapy
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A. |
Drug: Carboplatin
Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Radiation: Radiation Therapy Undergo radiation therapy
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
Drug: Cisplatin
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Drug: Isotretinoin Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Radiation: Radiation Therapy Undergo radiation therapy
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy. CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C. |
Drug: Carboplatin
Given IV
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Drug: Isotretinoin Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Radiation: Radiation Therapy Undergo radiation therapy
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma [ Time Frame: Up to 5 years ]The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined.
- Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) [ Time Frame: Up to 5 years ]The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals.
Secondary Outcome Measures :
- Tumor Response to Radiation Therapy for Patients With Medulloblastoma [ Time Frame: 12 weeks after treatment initiation ]Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses.
- Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) [ Time Frame: 12 weeks after treatment initiation ]Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335.
- Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma [ Time Frame: Up to 5 years ]The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined.
- Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET) [ Time Frame: Up to 5 years ]The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact.
- The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients [ Time Frame: 6 - 12 months post diagnosis ]Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
- The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients [ Time Frame: 24 - 36 months post diagnosis ]Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
- The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients [ Time Frame: 48 - 72 months post diagnosis ]Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
- The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients [ Time Frame: 6 - 12 months post diagnosis ]Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
- The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients [ Time Frame: 24 - 36 months post diagnosis ]Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
- The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients [ Time Frame: 48 - 72 months post diagnosis ]Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported.
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients [ Time Frame: 6 - 12 months post diagnosis ]Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients [ Time Frame: 24 - 36 months post diagnosis ]Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335.
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients [ Time Frame: 48 - 72 months post diagnosis ]Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients [ Time Frame: 6 - 12 months post diagnosis ]Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients [ Time Frame: 24 - 36 months post diagnosis ]Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients [ Time Frame: 48 - 72 months post diagnosis ]Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 3 Years to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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Newly diagnosed, previously untreated: (1) M0 medulloblastoma with > 1.5 cm^2 residual; (2) M+ medulloblastoma; patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor
- As of amendment # 2, enrollment of patients with supratentorial PNET has been discontinued
- All patients with M4 disease are not eligible
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A pre-operative magnetic resonance imaging (MRI) scan of the brain with and without contrast is required; NOTE: computed tomography (CT) scans are NOT sufficient for study eligibility
- Post-operative head MRI scan with and without contrast (preferably within 72 hours post-surgery); for patients who undergo stereotactic biopsy only, either a pre or post-operative MRI is sufficient; for patients with M2 and M3 disease, a post-op MRI is strongly encouraged, but not mandatory
- Spinal MRI imaging with and without gadolinium is required within 10 days of surgery if done pre-operatively or within 28 days of surgery if done post-operatively; for posterior fossa tumors, pre-operative MRI scans are preferred
- Lumbar cerebrospinal fluid (CSF) cytology examination must be obtained pre-operatively or within 31 days following surgery; the optimal time for obtaining CSF is prior to surgery or 1-3 weeks following surgery; ventricular CSF (either pre- or post-op) may be used only if a post-operative spinal tap is contraindicated; if a spinal tap is contraindicated and there is no ventricular CSF available, then CSF cytology can be waived for patients with supratentorial tumors or if there is documentation of spinal subarachnoid metastases (M3); patients who are categorized as M1 must have either an intra-operative positive CSF (via lumbar puncture at the end of the procedure) or a positive lumbar CSF obtained > 7 days post-operatively
- Patients must have a Karnofsky performance level of >= 30 for patients > 16 years of age or a Lansky performance scale of >= 30 for patients =< 16 years of age and life expectancy > 8 weeks
- No previous chemotherapy or radiation therapy
- Corticosteroids should not be used during chemotherapy administration as an antiemetic
- Selected strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (cytochrome P450 3A4) include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort; the use of these drugs should be avoided with vincristine (vincristine sulfate)
- CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution when taking cyclophosphamide; aprepitant should also be used with caution with etoposide or vincristine chemotherapy
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Cisplatin should be used with caution with nephrotoxic drug; aminoglycoside should be avoided or used with caution during or shortly after cisplatin administration and concomitant use with amphotericin B should probably also be avoided; patients receiving cisplatin and other potentially ototoxic drugs such as aminoglycoside or loop diuretics concomitantly should be closely monitored for signs of ototoxicity
- Plasma levels of anticonvulsant agents should be monitored and doses adjusted during therapy with cisplatin
- No other experimental therapy is permitted while on study
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Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:
- 0.8 mg/dL (2 to < 6 years of age)
- 1.0 mg/dL (6 to < 10 years of age)
- 1.2 mg/dL (10 to < 13 years of age)
- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
- Total bilirubin < 1.5 x upper limit of normal (ULN) for age
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age; for patients on anti-seizure medications, SGOT (AST) or SGPT (ALT) must be < 5 x ULN
- Absolute neutrophil count (ANC) >= 1,000/uL
- Platelets >= 100,000/uL (untransfused)
- Hemoglobin >= 8 g/dl (may be transfused)
- Female patients who are post-menarchal must have a negative pregnancy test; lactating female patients must agree not to breast-feed while on this trial; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
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): NCT00392327
Locations
Show 196 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | James M Olson | Children's Oncology Group |
Study Documents (Full-Text)
Documents provided by Children's Oncology Group:
Documents provided by Children's Oncology Group:
Study Protocol and Statistical Analysis Plan [PDF] April 11, 2018
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00392327 |
| Other Study ID Numbers: |
ACNS0332 NCI-2009-00336 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 07-271 CDR0000511991 COG-ACNS0332 ACNS0332 ( Other Identifier: Children's Oncology Group ) ACNS0332 ( Other Identifier: CTEP ) R01CA114567 ( U.S. NIH Grant/Contract ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | October 26, 2006 Key Record Dates |
| Results First Posted: | August 7, 2020 |
| Last Update Posted: | January 9, 2023 |
| Last Verified: | January 2023 |
Additional relevant MeSH terms:
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Medulloblastoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neuroectodermal Tumors, Primitive Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Vitamin A Cyclophosphamide Cisplatin Carboplatin Vincristine |
Tretinoin Isotretinoin Lenograstim Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Vitamins Micronutrients Adjuvants, Immunologic |