Combination Chemotherapy in Treating Children With Progressive Brain Tumors - Full Text View

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens and comparing how well they work in treating children with low-grade astrocytomas or other residual tumors of the brain.

Condition	Intervention	Phase
Brain Tumors Central Nervous System Tumors	Drug: carboplatin Drug: lomustine Drug: procarbazine hydrochloride Drug: thioguanine Drug: vincristine sulfate	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Chemotherapy for Progressive Low Grade Astrocytoma in Children Less Than Ten Years Old

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Thioguanine Procarbazine hydrochloride Procarbazine Vincristine sulfate Lomustine Carboplatin

Genetic and Rare Diseases Information Center resources: Glioma Optic Pathway Glioma Childhood Brain Stem Glioma Cerebellar Astrocytoma, Childhood Cerebral Astrocytoma, Childhood Neuroepithelioma

U.S. FDA Resources

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

Primary Outcome Measures:

Event Free Survival [ Time Frame: Time from study entry until disease progression, death without progression of disease, occurrence of a second malignant neoplasm or last follow-up, whichever comes first, assessed up to 5 years ] [ Designated as safety issue: No ]
Compare the event-free survival as a result of treatment with either CV or TPCV

Secondary Outcome Measures:

Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Defined as the time to death from any cause.


Enrollment:	428
Study Start Date:	April 1997
Study Completion Date:	April 2012
Primary Completion Date:	February 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Regimen A (CV Chemotherapy) Induction will consist of 10 weeks of therapy (carboplatin, vincristine sulfate),followed by 2 weeks without chemotherapy. Induction should only be interrupted in the event of grade 3 neurotoxicity, grade 2 renal toxicity, grade 4 hematologic toxicity, or tumor progression. Maintenance-Four Courses (2 cycles/course) commences on Day 84 (week 12) of Induction or when peripheral counts recover with ANC >1,000/$L and platelet count >100,000/$L. Each cycle will consist of 4 weekly doses of carboplatin, three weekly doses of vincristine sulfate (given concomitantly with the first 3 weeks of carboplatin), followed by two weeks of rest for a total of 6 weeks. Maintenance will continue for a total of 8 cycles.	Drug: carboplatin Given IV Other Names: Paraplatin NSC-241240 Drug: vincristine sulfate Given PO and IV Other Names: Oncovin NSC-675574
Experimental: Regimen B (TPCV Chemotherapy) Each cycle of chemotherapy consists of 4 days of oral chemotherapy (Thioguanine, procarbazine hydrochloride, Lomustine and Vincristine sulfate beginning Day 0, followed by vincristine sulfate IV on Days 14 and 28. The cycle is repeated every 6 weeks (42 days). A total of 8 cycles will be given.	Drug: lomustine Given IV Other Names: CCNU NSC-79037 Drug: procarbazine hydrochloride Given PO Other Names: Matulane NSC-77213 Drug: thioguanine Given PO Other Names: 6-TG NSC-752 Drug: vincristine sulfate Given PO and IV Other Names: Oncovin NSC-675574

Arms

Assigned Interventions

Experimental: Regimen A (CV Chemotherapy)

Induction will consist of 10 weeks of therapy (carboplatin, vincristine sulfate),followed by 2 weeks without chemotherapy. Induction should only be interrupted in the event of grade 3 neurotoxicity, grade 2 renal toxicity, grade 4 hematologic toxicity, or tumor progression. Maintenance-Four Courses (2 cycles/course) commences on Day 84 (week 12) of Induction or when peripheral counts recover with ANC >1,000/$L and platelet count >100,000/$L. Each cycle will consist of 4 weekly doses of carboplatin, three weekly doses of vincristine sulfate (given concomitantly with the first 3 weeks of carboplatin), followed by two weeks of rest for a total of 6 weeks. Maintenance will continue for a total of 8 cycles.

Drug: carboplatin

Given IV

Other Names:

Paraplatin
NSC-241240

Drug: vincristine sulfate

Given PO and IV

Other Names:

Oncovin
NSC-675574

Experimental: Regimen B (TPCV Chemotherapy)

Each cycle of chemotherapy consists of 4 days of oral chemotherapy (Thioguanine, procarbazine hydrochloride, Lomustine and Vincristine sulfate beginning Day 0, followed by vincristine sulfate IV on Days 14 and 28. The cycle is repeated every 6 weeks (42 days). A total of 8 cycles will be given.

Drug: lomustine

Given IV

Other Names:

CCNU
NSC-79037

Drug: procarbazine hydrochloride

Given PO

Other Names:

Matulane
NSC-77213

Drug: thioguanine

Given PO

Other Names:

6-TG
NSC-752

Drug: vincristine sulfate

Given PO and IV

Other Names:

Oncovin
NSC-675574

Detailed Description:

OBJECTIVES:

Compare the event free survival as a result of treatment with carboplatin and vincristine versus thioguanine, procarbazine, lomustine, and vincristine in children with progressive brain tumors.
Estimate tumor response rates to each regimen of chemotherapy in these patients.
Determine toxic effects and quality of life of children treated with each regimen of chemotherapy.
Investigate biological and clinical factors which may predict tumor response and early progression (tumor size, location, pathologic subtype, cytogenetics, and proliferative index by MIB-1 (Ki67)) in these patients.
Investigate factors contributing to neuropsychological and endocrine status of children with brain tumors treated without irradiation.

OUTLINE: This is a randomized study. Patients are stratified according to site of disease, status at entry, and pathology. Patients are randomized to one of two treatment arms. Patients with neurofibromatosis are nonrandomly assigned to arm II.

Arm I: Patients receive induction with carboplatin and vincristine for 10 weeks followed by 2 weeks of rest. Induction is followed by 8 courses of maintenance beginning on day 84 of induction or upon hematopoietic recovery. Each course consists of 4 weekly doses of carboplatin and 3 weekly doses of vincristine (given concurrently with the first 3 weeks of carboplatin), followed by 2 weeks of rest.
Arm II: Patients receive oral thioguanine, procarbazine, and lomustine on days 0-4, followed by vincristine IV on days 14 and 28. Treatment continues every 6 weeks for a maximum of 8 courses.

PROJECTED ACCRUAL: A total of 280-340 patients will be accrued over 4 years.

Eligibility


Ages Eligible for Study:	up to 9 Years (Child)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed low grade residual astrocytomas or other eligible residual tumors of the brain interpreted as low grade (WHO grades I and II) such as the following:
- Glial Tumors
  - Astrocytic tumors
    - Low grade astrocytoma (variants: fibrillary, protoplasmic, gemistocytic)
    - Pilocytic astrocytoma
    - Pleomorphic xanthoastrocytomas
    - Subependymal giant cell astrocytoma
    - Infantile desmoplastic astrocytoma
  - Low grade oligodendroglial tumors
    - Low grade oligodendroglioma
  - Low grade mixed gliomas
    - Oligo-astrocytoma
- Neuronal Tumors
  - Ganglioglioma (excluding tumors with anaplastic astrocytic components)
  - Infantile desmoplastic ganglioglioma
- Chiasmatic-hypothalamic tumor without histologic confirmation
All of the following diagnostic tests (radiological or clinical evidence of progression, surgery, or confirmatory MRI) must be carried out within 6 weeks of enrollment into this study
Progressive disease following surgical excision based on clear radiological or clinical evidence of progression, or an incomplete excision (less than 95% or greater than 1.5 cm2) with necessity to begin treatment because of a risk of neurologic impairment with progression
Chiasmatic lesions that have contiguous extensions of tumor into other regions of the visual pathways demonstrated on contrast MRI will be eligible for study without histopathological confirmation
Patients with neurofibromatosis who have radiographic diagnosis of chiasmatic-hypothalamic tumor are eligible for the study, without requiring a biopsy confirmation of tumor histology, but not unless tumor progression is documented radiographically
No intrinsic brain stem tumors of the pons or isolated optic nerve tumors without definitive involvement of the optic chiasm

PATIENT CHARACTERISTICS:

Age:

Under 10

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count greater than 1,000/mm^3 (arm II)
Platelet count greater than 100,000/mm^3 (arm II)

Hepatic:

Not specified

Renal:

Creatinine less than 1.5 times upper limit of normal for age OR
Creatinine clearance or radioisotope GFR greater than 70 mL/min or equivalent GFR as determined by the institutional normal range

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy for the tumor

Endocrine therapy:

Prior corticosteroid therapy allowed

Radiotherapy:

No prior radiotherapy for the tumor

Surgery:

See Disease characteristics

Other:

Prior diuretic therapy allowed

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: NCT00002944

Show 204 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Study Chair:	Joann Ater, MD	M.D. Anderson Cancer Center

More Information

Publications:

Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR, Lazarus KH, Packer RJ, Prados M, Sposto R, Vezina G, Wisoff JH, Pollack IF. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children's Oncology Group. J Clin Oncol. 2012 Jul 20;30(21):2641-7. doi: 10.1200/JCO.2011.36.6054. Epub 2012 Jun 4.


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00002944 History of Changes
Other Study ID Numbers:	A9952 CCG-A9952 POG-A9952 CCG-9952 CDR0000065394
Study First Received:	November 1, 1999
Last Updated:	September 6, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:


recurrent childhood brain stem glioma recurrent childhood visual pathway glioma recurrent childhood cerebellar astrocytoma	recurrent childhood cerebral astrocytoma childhood low-grade cerebellar astrocytoma childhood low-grade cerebral astrocytoma

Additional relevant MeSH terms:


Neoplasms Brain Neoplasms Astrocytoma Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial	Neoplasms, Nerve Tissue Carboplatin Vincristine Lomustine Thioguanine Procarbazine Antineoplastic Agents Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on September 23, 2016