Phase II Randomized Study of Induction with CTX/VCR/VP-16/CDDP vs IFF/VCR/VP-16/CBDCA Followed by Maintenance with CBDCA/VCR/CTX/VP-16, with Delayed Radiotherapy as Appropriate, in Infants with Previously Untreated Malignant Brain Tumors
Combination Chemotherapy Followed by Radiation Therapy in Young Children with Previously Untreated Brain Tumors
Basic Trial Information
|Phase II||Treatment||Closed||under 36 months at diagnosis||NCI||CCG-9921|
I. Estimate the response rate, freedom from progression, and toxicity experienced by children less than 36 months of age with newly diagnosed malignant CNS tumors treated with high-dose cyclophosphamide/vincristine/etoposide/cisplatin vs. ifosfamide/vincristine/etoposide/carboplatin given in conjunction with granulocyte colony stimulating factor. II. Estimate the disease-control interval using these two regimens without cranial irradiation in children who have no apparent residual tumor after initial surgery or who have had a complete response to induction chemotherapy (excluding those with metastatic disease at diagnosis). III. Estimate the disease-control interval using these two regimens with cranial irradiation to treat patients who have residual tumor following induction chemotherapy or metastatic disease at diagnosis. IV. Evaluate the feasibility of using a reduced dose of craniospinal irradiation (2,340 cGy) in children with nonmetastatic, nonprogressive medulloblastoma/PNET who require irradiation. V. Estimate the response rate, disease-control interval, recurrence-free survival, and overall survival of children treated with radiotherapy following disease progression on chemotherapy. VI. Determine whether clinical or biologic studies can predict response to or failure of chemotherapy, with a specific evaluation of the prognostic significance of tumor cell DNA content (ploidy). VII. Evaluate the tumor cytogenetic abnormalities in this group of children and correlate these abnormalities with histology and DNA content. VIII. Document the late effects (specifically cognitive function and endocrine function) of chemotherapy and radiotherapy in this patient population.
Histologically confirmed (except some brainstem tumors) malignant brain tumors of the following types: PNET, including but not limited to: Medulloblastoma Pineoblastoma Cerebral neuroblastoma Ependymoblastoma High-grade astrocytoma, including: Glioblastoma multiforme Anaplastic astrocytoma Small cell glioblastoma Giant cell glioblastoma Gliosarcoma Ependymoma Choroid plexus carcinomas Malignant CNS germ cell tumors Primary sarcomas Brainstem glioma (selected) Brainstem tumors may be either: Diffuse tumors (defined below) regardless of histology OR Localized histologically documented anaplastic gliomas Diffuse tumors are defined as: Poorly demarcated tumors on CT with intrinsic involvement (greater than 50% intra-axial) of the entire pons, the pons and the medulla, the pons and the midbrain, or the entire brainstem OR Tumors that on MRI intrinsically involve the pons, the pons and the medulla, the pons and the midbrain, or the entire brainstem Tumors involving the midbrain may also contiguously involve the thalamus or the upper cervical cord Histologic confirmation not required only if more than 50% of the tumor is intrinsic in brain stem The following tumors require biopsy-documented anaplastic histology: Tumors localized to midbrain alone on CT or MRI Tumors localized to cervicomedullary junction on CT or MRI Tumors with greater than 50% exophytic extension dorsally or laterally out of brainstem The following tumors are specifically excluded: Pleomorphic xanthoastrocytoma "Desmoplastic ganglioglioma" Oligodendroglioma of any grade Ganglioglioma of any grade Low-grade astrocytoma Daumas-Duport Grade I and most Grade II tumors Cerebellar astrocytomas (except frank glioblastomas) Myxopapillary ependymomas of the spinal cord Neuraxial metastasis of histologically benign papillomas Low-grade brainstem astrocytoma Primary CNS lymphoma Leukemic solid brain tumors (i.e., chloromas, granulocytic sarcomas) No more than 28 days between diagnostic surgery (or radiologic diagnosis of brainstem tumor) and initiation of protocol therapy
No prior therapy
Age: Under 36 months at diagnosis Performance status: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified
A total of 276 patients (up to 25 patients in each histologic category) will be accrued. If no responses are seen in the first 14 patients treated in a given category, accrual in that category will cease.
Randomized study. Patients are randomized for Induction on Arms I and II, then proceed to Maintenance. Patients with residual disease following Induction, with metastatic disease at diagnosis, or those without prior radiotherapy who recur or progress receive further therapy on Regimen A. Induction. Arm I: 4-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation. Vincristine, VCR, NSC-67574; Etoposide, VP-16, NSC-141540; Cisplatin, CDDP, NSC-119875; Cyclophosphamide, CTX, NSC-26271; with Mesna, NSC-113891; and Granulocyte Colony-Stimulating Factor (Amgen), G-CSF, NSC-614629. Arm II: 4-Drug Combination Chemotherapy with Urothelial Protection and Hematologic Toxicity Attenuation. VP-16; Carboplatin, CBDCA, NSC-241240; VCR; Ifosfamide, IFF, NSC-109724; with Mesna; and G-CSF. Maintenance: 3-Drug Combination Chemotherapy alternating with 2-Drug Combination Chemotherapy with Urothelial Protection. VCR; VP-16; CBDCA; alternating with VP-16; CTX; with Mesna. Regimen A: Radiotherapy. Local tumor irradiation with, as appropriate, craniospinal irradiation, using Co60 or 4-15 MV photons.
Leary SE, Zhou T, Holmes E, et al.: Histology predicts a favorable outcome in young children with desmoplastic medulloblastoma: a report from the children's oncology group. Cancer 117 (14): 3262-7, 2011.[PUBMED Abstract]
Geyer JR, Sposto R, Jennings M, et al.: Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol 23 (30): 7621-31, 2005.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
Children's Cancer Group
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.