Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma - Full Text View

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. 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.

Condition	Intervention	Phase
Childhood Infratentorial Ependymoma Childhood Supratentorial Ependymoma Newly Diagnosed Childhood Ependymoma	Drug: liposomal vincristine sulfate Other: clinical observation Radiation: 3-dimensional conformal radiation therapy Drug: carboplatin Drug: cyclophosphamide Drug: etoposide Drug: cisplatin Other: laboratory biomarker analysis	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment 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

Resource links provided by NLM:

Drug Information available for: Cyclophosphamide Vincristine sulfate Sulfate ion Etoposide Carboplatin Etoposide phosphate

Genetic and Rare Diseases Information Center resources: Ependymoma Glioma Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:

Event-free survival (EFS) defined as time to the first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Using Kaplan-Meier curves to estimate the observed EFS for the two randomization arms (post-radiation Maintenance arm and post-radiation Observation only arm). Log rank tests will be used to compare the observed EFS between the two randomization arms. Stratified log rank test will also be performed to examine the treatment difference with consideration and adjustment for the randomization groups.
Overall survival (OS) [ Time Frame: From the time of randomization to death, assessed up to 5 years ] [ Designated as safety issue: No ]
Using Kaplan-Meier curves to estimate the observed OS for the two randomization arms (post-radiation Maintenance arm and post-radiation Observation only arm). Log rank tests will be used to compare the observed OS between the two randomization arms. Stratified log rank test will also be performed to examine the treatment difference with consideration and adjustment for the randomization groups.

Secondary Outcome Measures:

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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Kaplan-Meier curves will be used to estimate the EFS and OS for patients who were non-randomly assigned to receive maintenance chemotherapy after incomplete resection
EFS and OS of children with supratentorial classic ependymoma who achieve a complete resection at first or second surgery or children who achieve a CR after induction chemotherapy assigned to observation [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Estimated using Kaplan-Meier curves for patients with supratentorial classic disease that achieve complete resection or CR to induction chemotherapy and are assigned to observation only.
Neurologic, neuropsychological, and endocrine long-term sequelae of surgery, conformal radiotherapy, and maintenance chemotherapy [ Time Frame: At 9, 30, and 60 months post diagnosis ] [ Designated as safety issue: Yes ]
Gene expression signatures and genomic alterations in pediatric ependymoma [ Time Frame: At the time of first or second surgery ] [ 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 (radiotherapy, chemotherapy) Patients undergo 3-dimensional conformal radiation therapy over 6-7 weeks. Patients then receive liposomal vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours on days 1-3; carboplatin on day 1, cisplatin IV over 1-8 hours on day 1; cyclophosphamide IV over 30-60 minutes on days 1-2 and filgrastim. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: liposomal vincristine sulfate Given IV Other Names: liposomal vincristine Marqibo vincristine liposomal vincristine sulfate liposome injection Radiation: 3-dimensional conformal radiation therapy Patients undergo conformal radiotherapy Other Names: 3D conformal radiation therapy 3D-CRT Drug: carboplatin Given IV Other Names: Carboplat CBDCA JM-8 Paraplat Paraplatin Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213 Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Other: laboratory biomarker analysis Optional correlative studies
Active Comparator: Arm II (radiotherapy) Patients undergo 3-dimensional conformal radiation therapy over 6-7 weeks.	Other: clinical observation Patients undergo observation Other Name: observation Radiation: 3-dimensional conformal radiation therapy Patients undergo conformal radiotherapy Other Names: 3D conformal radiation therapy 3D-CRT Other: laboratory biomarker analysis Optional correlative studies

Arms

Assigned Interventions

Experimental: Arm I (radiotherapy, chemotherapy)

Patients undergo 3-dimensional conformal radiation therapy over 6-7 weeks. Patients then receive liposomal vincristine sulfate IV on days 1, 8, and 15 (courses 1-3 only); etoposide IV over 1-2 hours on days 1-3; carboplatin on day 1, cisplatin IV over 1-8 hours on day 1; cyclophosphamide IV over 30-60 minutes on days 1-2 and filgrastim. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Drug: liposomal vincristine sulfate

Given IV

Other Names:

liposomal vincristine
Marqibo
vincristine liposomal
vincristine sulfate liposome injection

Radiation: 3-dimensional conformal radiation therapy

Patients undergo conformal radiotherapy

Other Names:

3D conformal radiation therapy
3D-CRT

Drug: carboplatin

Given IV

Other Names:

Carboplat
CBDCA
JM-8
Paraplat
Paraplatin

Drug: cyclophosphamide

Given IV

Other Names:

CPM
CTX
Cytoxan
Endoxan
Endoxana

Drug: etoposide

Given IV

Other Names:

EPEG
VP-16
VP-16-213

Drug: cisplatin

Given IV

Other Names:

CACP
CDDP
CPDD
DDP

Other: laboratory biomarker analysis

Optional correlative studies

Active Comparator: Arm II (radiotherapy)

Patients undergo 3-dimensional conformal radiation therapy over 6-7 weeks.

Other: clinical observation

Patients undergo observation

Other Name: observation

Radiation: 3-dimensional conformal radiation therapy

Patients undergo conformal radiotherapy

Other Names:

3D conformal radiation therapy
3D-CRT

Other: laboratory biomarker analysis

Optional correlative studies

Show Detailed Description

Eligibility


Ages Eligible for Study:	1 Year to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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
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
No prior treatment for ependymoma other than surgical intervention and corticosteroids

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01096368

Contacts


Contact: Amy A. Smith, MD	321-841-8560	amy.smith@orlandohealth.com

Show 155 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Amy A. Smith, MD	Children's Oncology Group

More Information

No publications provided


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT01096368 History of Changes
Other Study ID Numbers:	ACNS0831, NCI-2011-02029, COG-ACNS0831, CDR0000668560, U10CA098543
Study First Received:	March 30, 2010
Last Updated:	February 23, 2015
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Ependymoma Glioma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors	Vincristine Antimitotic Agents Antineoplastic Agents Antineoplastic Agents, Phytogenic Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses Tubulin Modulators

ClinicalTrials.gov processed this record on March 03, 2015