Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma
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Purpose
RATIONALE: Drugs used in chemotherapy, 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 or by stopping them from dividing. 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 with radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.
PURPOSE: This randomized phase III trial is studying maintenance chemotherapy to see how well it works compared to observation following induction chemotherapy and radiation therapy in treating young patients with newly diagnosed ependymoma.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors |
Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Drug: vincristine sulfate Other: clinical observation Radiation: 3-dimensional conformal radiation therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Masking: 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 |
- Event-free survival (EFS) [ Designated as safety issue: No ]
- Overall survival (OS) [ Designated as safety issue: No ]
- EFS and 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 [ Designated as safety issue: No ]
- EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second resection or children who achieve a CR to short-course induction chemotherapy following first surgery [ Designated as safety issue: No ]
- Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, conformal radiotherapy, and maintenance chemotherapy comprising vincristine sulfate, cisplatin, etoposide, and cyclophosphamide as compared to those patients treated on COG- ... [ Designated as safety issue: No ]
- Gene expression signatures and genomic alterations in pediatric ependymoma [ Designated as safety issue: No ]
- Prognostic molecular signatures and genomic alterations in ependymomas [ Designated as safety issue: No ]
| Estimated Enrollment: | 400 |
| Study Start Date: | March 2010 |
| Estimated Primary Completion Date: | March 2020 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours on days 1-3; cisplatin IV over 1-8 hours on day 1; and cyclophosphamide IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
|
Drug: cisplatin
Given IV
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Drug: vincristine sulfate
Given IV
Radiation: 3-dimensional conformal radiation therapy
Patients undergo conformal radiotherapy
|
|
Active Comparator: Arm II
Patients undergo conformal radiotherapy over 6-7 weeks.
|
Other: clinical observation
Patients undergo observation
Radiation: 3-dimensional conformal radiation therapy
Patients undergo conformal radiotherapy
|
Detailed Description:
OBJECTIVES:
Primary
- To determine the event-free survival (EFS) and overall survival (OS) of children with completely resected ependymoma treated with maintenance chemotherapy comprising vincristine sulfate, cisplatin, etoposide, and cyclophosphamide (VCEC) versus observation following post-operative conformal radiotherapy (cRT).
Secondary
- To estimate the EFS and 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 who are non-randomly assigned to cRT followed by VCEC.
- To further evaluate the EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second resection or children who achieve a CR to short-course induction chemotherapy following first surgery.
- To determine the neurologic, neuropsychological, and endocrine long-term sequelae of surgery, cRT, and VCEC as compared to those patients treated on COG-ACNS0121.
- To determine biologic prognostic factors in childhood ependymoma by utilizing genomic profiles via comparative genomic hybridization and single-nucleotide polymorphism arrays, and microarray gene expression profiling analysis on initial tumor samples and correlating this with clinical outcome.
- To evaluate prognostic immune-function gene expression in ependymomas.
- To build upon the data derived from COG-ACNS0121 to develop genotypically based classification signatures and to correlate these to WHO grade, location, extent of resection, treatment, EFS, and OS.
- To evaluate telomere maintenance as a prognostic marker.
OUTLINE: This is a multicenter study. Patients are stratified according to extent of resection at initial surgery (total vs near total resection), tumor histology, and tumor location (infratentorial primary tumor vs supratentorial anaplastic tumor). Patients are randomized to 1 of 2 treatment arms. Patients with supratentorial classic tumor are assigned to arm II.
All patients receive induction chemotherapy comprising vincristine sulfate IV on days 1 and 8, carboplatin IV over 15-60 minutes on day 1, and cyclophosphamide IV over 30-60 minutes on days 1-2. Patients also receive etoposide IV over 60-120 minutes on days 1-3 of course 2 only. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease, partial response, or locally progressive disease and who are deemed potentially resectable undergo surgery within 15 days after completion of induction chemotherapy.
- Arm I: Patients undergo conformal radiotherapy over 6-7 weeks. Patients then receive vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours on days 1-3; cisplatin IV over 1-8 hours on day 1; and cyclophosphamide IV over 30-60 minutes on days 1-2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients undergo conformal radiotherapy over 6-7 weeks. Some patients undergo blood and tissue sample collection before treatment and after surgery for gene expression microarray, genomic hybridization array, and other correlative studies.
After completion of study therapy, patients are followed up every 4 months for 5 years.
Eligibility| Ages Eligible for Study: | 1 Year to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed intracranial ependymoma meeting the following criteria:
- Newly diagnosed disease
Classic ependymoma (WHO II) or anaplastic ependymoma (WHO III), including the following subtypes:
- Clear cell
- Papillary
- Cellular
- Combination of the above
- No diagnosis of spinal cord ependymoma, myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed glioma
Has undergone surgical resection of the primary tumor
- More than 1 attempted resection allowed
No metastatic disease by MRI or cerebrospinal fluid (CSF) cytology
- CSR cytology from a ventriculostomy or permanent VP shunt that reveals the presence of tumor cells is indicative of metastatic disease
No evidence of non-contiguous spread beyond the primary site as determined by pre- or post-operative MRI of brain, pre- or post-operative MRI of the spine, and post-operative CSF cytology obtained from the lumbar CSF space
- Lumbar CSF examination may be waived if deemed to be medically contraindicated
PATIENT CHARACTERISTICS:
ECOG performance status (PS) 0-2
- Karnofsky PS for patients > 16 years of age
- Lansky PS for patients ≤ 16 years of age
- ANC ≥ 1,000/μL
- Platelet count ≥ 100,000/μL (transfusion independent)
Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- 0.4 mg/dL (1 month to < 6 months of age)
- 0.5 mg/dL (6 months to < 1 year of age)
- 0.6 mg/dL (1 to 2 years of age)
- 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 times upper limit of normal (ULN) (≤ 3 times ULN for patients with Gilbert syndrome or hemolytic anemia)
- AST or ALT < 3 times ULN
Adequate cardiac function defined as 1 of the following:
- Shortening fraction ≥ 27% by ECHO
- Ejection fraction ≥ 50% by gated radionuclide study.
Not pregnant or nursing
- Patients who agree to stop nursing while on this study are allowed
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior treatment for ependymoma other than surgical intervention and corticosteroids
Contacts and Locations
Show 140 Study Locations| Principal Investigator: | Amy A. Smith, MD | University of Florida |
More Information
Additional Information:
No publications provided
| Responsible Party: | Gregory H. Reaman, Children's Oncology Group - Group Chair Office |
| ClinicalTrials.gov Identifier: | NCT01096368 History of Changes |
| Other Study ID Numbers: | CDR0000668560, COG-ACNS0831 |
| Study First Received: | March 30, 2010 |
| Last Updated: | November 13, 2012 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
childhood infratentorial ependymoma childhood supratentorial ependymoma newly diagnosed childhood ependymoma |
Additional relevant MeSH terms:
|
Ependymoma Nervous System Neoplasms Central Nervous System Neoplasms Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases Etoposide phosphate Cisplatin |
Cyclophosphamide Etoposide Vincristine Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists |
ClinicalTrials.gov processed this record on May 22, 2013