Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
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| ClinicalTrials.gov Identifier: NCT01096368 |
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Recruitment Status :
Active, not recruiting
First Posted : March 31, 2010
Results First Posted : March 2, 2023
Last Update Posted : March 2, 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:
The primary aim of this randomized phase III trial was to study whether the addition of maintenance chemotherapy delivered after surgical resection and focal radiation would be better than surgery and focal radiation alone. The trial also studied if patients who received induction chemotherapy and then either achieved a complete response or went on to have a complete resection would also benefit from maintenance chemotherapy. Children ages 1-21 years with newly diagnosed intracranial ependymoma were included. There were 2 arms that were not randomized. One arm studied patients with Grade II tumors located in the supratentorial compartment that were completely resected. One arm studied patients with residual tumor and those patients all received maintenance chemotherapy after focal radiation. Chemotherapy drugs, such as vincristine sulfate, carboplatin, cyclophosphamide, etoposide, and cisplatin, 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. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving chemotherapy in combination with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Anaplastic Ependymoma Brain Ependymoma Cellular Ependymoma Clear Cell Ependymoma Ependymoma Papillary Ependymoma | Radiation: 3-Dimensional Conformal Radiation Therapy Drug: Carboplatin Drug: Cisplatin Other: Clinical Observation Drug: Cyclophosphamide Drug: Etoposide Biological: Filgrastim Other: Laboratory Biomarker Analysis Drug: Mesna Drug: Vincristine | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 479 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years |
| Actual Study Start Date : | March 29, 2010 |
| Actual Primary Completion Date : | December 31, 2021 |
| Estimated Study Completion Date : | December 31, 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (chemotherapy, observation)
Patients with classic histology(WHO Grade II) supratentorial ependymoma who have undergone microscopic gross total resection (GTR1) or achieved CR either after first or second resection or after post-operative induction chemotherapy are assigned to observation. For patients without GTR1, induction chemotherapy is comprised of vincristine intravenously (IV) over 1 minute on days 1 and 8 of cycles 1 and 2, carboplatin IV over 15-60 minutes on day 1 of cycles 1 and 2, and cyclophosphamide IV over 30-60 minutes on days 1-2 of cycle 1 only. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of cycle 2 only. Cycle 1 continues for 3 weeks and cycle 2 continues for 4 weeks in the absence of disease progression or unacceptable toxicity.
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Drug: Carboplatin
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Biological: Filgrastim Given SC or IV
Other Names:
Other: Laboratory Biomarker Analysis Optional correlative studies Drug: Mesna Given IV
Other Names:
Drug: Vincristine Given IV
Other Names:
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Experimental: Arm II (radiotherapy, chemotherapy)
Patients with supratentorial ependymoma (Grade II without GTR1 or Grade III) or any infratentorial ependymoma who have undergone gross or near total resection (GTR or NTR) or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks followed by maintenance chemotherapy. Maintenance chemotherapy comprised of vincristine IV on days 1, 8, and 15 of cycles 1-3 only, etoposide IV over 60-120 minutes on days 1-3, cisplatin IV over 1-8 hours on day 1, and cyclophosphamide IV over 30-60 minutes on days 2-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Patients undergo conformal radiotherapy
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Biological: Filgrastim Given SC or IV
Other Names:
Other: Laboratory Biomarker Analysis Optional correlative studies Drug: Mesna Given IV
Other Names:
Drug: Vincristine Given IV
Other Names:
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Active Comparator: Arm III (radiotherapy, observation)
Patients with supratentorial ependymoma (Grade II without GTR1 or ST Grade III) or any infratentorial ependymoma (Grade II or III) who have undergone gross or near total resection or achieved CR either after first or second resection or after post-operative induction chemotherapy are randomized to undergo conformal radiotherapy over 6-7 weeks and then undergo observation. Patients without GTR or NTR at enrollment require induction chemotherapy (see Arm I) and possibly second surgery before randomization.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Patients undergo conformal radiotherapy
Other Names:
Other: Clinical Observation Patients undergo observation
Other Name: observation Other: Laboratory Biomarker Analysis Optional correlative studies |
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Active Comparator: ARM IV (radiotherapy, chemotherapy)
Patients with subtotal resection after induction chemotherapy (see Arm I) and second surgery are nonrandomly assigned to Arm II treatment.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Patients undergo conformal radiotherapy
Other Names:
Drug: Cisplatin Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Biological: Filgrastim Given SC or IV
Other Names:
Other: Laboratory Biomarker Analysis Optional correlative studies Drug: Mesna Given IV
Other Names:
Drug: Vincristine Given IV
Other Names:
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Primary Outcome Measures :
- Event-free Survival (EFS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only [ Time Frame: Up to 10 years after enrollment. 5-year estimates of EFS are presented ]Kaplan-Meier estimates of EFS are calculated from randomization date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) is conveyed by the hazard ratio and 90.46% stagewise adjusted Wald confidence interval.
- Overall Survival (OS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only [ Time Frame: Up to 10 years after enrollment. 5-year estimates of OS are presented. ]Kaplan-Meier estimates of OS are calculated from randomization date to death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) is conveyed by the hazard ratio and 90.46% stagewise adjusted Wald confidence interval.
Other Outcome Measures:
- EFS in Children Who Have Completely Resected Ependymoma at Initial Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only [ Time Frame: Up to 10 years after enrollment. 5-year estimates of EFS are presented. ]Kaplan-Meier estimates of EFS are calculated from randomization date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval.
- EFS With Incomplete Resection After Initial Surgery, Then Achieved CR After Induction Chemotherapy or GTR/NTR After Second Surgery and Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only [ Time Frame: Up to 10 years after enrollment. 5-year estimates of EFS are presented. ]Kaplan-Meier estimates of EFS are calculated from randomization date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval.
- OS in Children Who Have Completely Resected Ependymoma at Initial Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only. [ Time Frame: Up to 10 years after enrollment. 5-year estimates of OS are presented. ]Kaplan-Meier estimates of OS are calculated from randomization date to death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval.
- OS in Children With Incomplete Resection After Initial Surgery Who Then Achieved CR After Induction Chemotherapy or GTR/NTR After Second Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only [ Time Frame: Up to 10 years after enrollment. 5-year estimates of OS are presented. ]Kaplan-Meier estimates of OS are calculated from randomization date to death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval.
- EFS of Children With Incompletely Resected Ependymoma Who Are Unable to Achieve a Complete Response (CR) by Post-operative Induction Chemotherapy or by Second Surgery and Who Are Non-randomly Assigned to Receive Maintenance Chemotherapy [ Time Frame: Up to 10 years after enrollment. 5-year estimates of EFS are presented. ]The Kaplan-Meier estimate of EFS is calculated from enrollment date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
- OS of Children With Incompletely Resected Ependymoma Who Are Unable to Achieve a Complete Response (CR) by Post-operative Induction Chemotherapy or by Second Surgery and Who Are Non-randomly Assigned to Receive Maintenance Chemotherapy [ Time Frame: Up to 10 years after enrollment. 5-year estimates of OS are presented. ]The Kaplan-Meier estimate of OS is calculated from enrollment date to death from any cause.
- EFS of Children With Supratentorial Classic Ependymoma Who Achieve Complete Resection at First or Second Surgery or Children Who Achieve Complete Response (CR) After Induction Chemo and Who Are Non-randomly Assigned to Observation [ Time Frame: Up to 10 years after enrollment. 5-year estimates of EFS are presented. ]The Kaplan-Meier estimate of EFS is calculated from enrollment date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause.
- OS of Children With Supratentorial Classic Ependymoma Who Achieve Complete Resection at First or Second Surgery or Children Who Achieve Complete Response (CR) After Induction Chemo and Who Are Non-randomly Assigned to Observation [ Time Frame: Up to 10 years after enrollment. 5-year estimates of OS are presented. ]The Kaplan-Meier estimate of OS is calculated from enrollment date to death from any cause.
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| Ages Eligible for Study: | 12 Months to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients must be newly diagnosed with histologically confirmed intracranial ependymoma; patients with classic ependymoma (WHO II) or anaplastic ependymoma (WHO III) are eligible, as are various subtypes described as clear cell, papillary, cellular or a combination of the above
- There is no minimum performance level; children with ependymoma may suffer neurologic sequelae as a result of their tumor or surgical measures taken to establish a diagnosis and resect the tumor; in the majority of cases, there is neurologic recovery; neurologic recovery is not likely to be impeded by protocol therapy
- REGULATORY: All patients and/or their parents or legal guardians must sign a written informed consent
- REGULATORY: All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
- Patients with evidence of metastatic disease will be excluded; any evidence of non-contiguous spread beyond the primary site as determined by pre or post-operative magnetic resonance (MR) imaging of brain, pre or post-operative MR imaging of the spine, and post-operative cerebrospinal fluid (CSF) cytology obtained from the lumbar CSF space (the requirement for lumbar CSF examination may be waived if deemed to be medically contraindicated); CSF cytology from a ventriculostomy or permanent ventriculoperitoneal (VP) shunt that reveals the presence of tumor cells is indicative of metastatic disease
- Patients with a diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed glioma are NOT eligible
- No prior treatment other than surgical intervention and corticosteroids; patients are allowed to have had more than one attempt at resection prior to enrollment
- Pregnant female patients are not eligible for this study
- Post-menarchal females may not participate unless a pregnancy test with a negative result has been obtained
- Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Lactating females may not participate unless they have agreed not to breastfeed a child while on this study
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): NCT01096368
Locations
Show 209 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Amy A Smith | 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] February 27, 2020
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT01096368 |
| Other Study ID Numbers: |
ACNS0831 NCI-2011-02029 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 10-01676 COG-ACNS0831 CDR0000668560 ACNS0831 ( Other Identifier: Children's Oncology Group ) ACNS0831 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | March 31, 2010 Key Record Dates |
| Results First Posted: | March 2, 2023 |
| Last Update Posted: | March 2, 2023 |
| Last Verified: | March 2023 |
Additional relevant MeSH terms:
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Ependymoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Cyclophosphamide Cisplatin Carboplatin Etoposide Vincristine Etoposide phosphate |
Podophyllotoxin Lenograstim Mesna Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors |