ACNS0332, Efficacy of Carboplatin administered Concomitantly with Radiation and Isotretinoin as a Prop-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients.
The treatment plan will begin within 31 days after surgery (to remove the tumor) and will involve a combination of radiation therapy and chemotherapy. Participants will receive 1 of 4 different treatment plans. The first stage of therapy is called chemoradiotherapy. all subjects will receive a combination of radiation therapy and chemotherapy to kill the cancer cells that are left over after surgery. This stage of therapy will take 6 weeks. Some subjects will have an extra chemotherapy drug, carboplatin, added to this treatment phase.
in the second stage of therapy, called Maintenance, all subjects will receive a combination of chemotherapy drugs. Maintenance therapy will last 6 months. The goal of maintenance therapy is to kill any remaining cancer cells that are left over from chemoradiotherapy. Some subjects will have an extra chemotherapy drug, isotretinoin, added to their regimen of chemotherapy drugs during this stage.
only some subjects will go onto a third stage of therapy, called Continuation. Continuation therapy will consist of 6 more months of therapy with the drug isotretinoin.
The stages of therapy and chemotherapy drugs that subjects receive will depend upon which treatment arm he/she is assigned to. all subjects will receive the standard therapy for medulloblastoma, but some subjects will receive additional drugs during their course of therapy.
The four treatment arms are as follows:
arm a: will receive standard chemoradiotherapy (radiation therapy and the drug vincristine). Subjects will then receive standard Maintenance chemotherapy.
arm B: will receive chemoradiotherapy plus the experimental drug carboplatin. Subjects will then receive standard Maintenance chemotherapy.
arm C: will receive standard chemoradiotherapy. Subjects will then receive Maintenance therapy with the addition of the drug isotretinoin and Continuation therapy with isotretinoin.
arm D: will receive chemoradiotherapy plus the experimental drug carboplatin. Subjects will then receive Maintenance therapy with the addition of the drug isotretinoin and Continuation therapy with isotretinoin.
Age greater than or equal to 3 and less than 22 years at the time of diagnosis. Newly diagnosed, previously untreated: (1) M0 Medulloblastoma with >1.5 cm2 residual; (2) M+ Medulloblastoma; (3) M0 or M+ Supratentorial PNET (including pineoblastoma). Patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor. A pre-operative MRI scan of the brain with and without contrast. Post-operative head MRI scan with and without contrast is required (preferably within 72 hours post-surgery). Spinal MRI imaging with and without gadolinium is required within 10 days of surgery if done preoperatively or within 28 days of surgery if done post-operatively. Lumbar CSF cytology examination must be obtained pre-operatively or within 31 days following surgery. Normal performance status and life expectancy > 8 weeks. No previous chemotherapy or radiation therapy. Patients taking Accutane (Isotretinoin) for acne must discontinue drug use with this indication prior to enrollment. Corticosteroids should not be used during chemotherapy administration as an antiemetic because of their effect on the blood-brain barrier. Isotretinoin is contraindicated in patients with parabens allergy as the capsule is preserved with the agent and patients with soybean allergy since Isotretinoin is suspended in soybean oil. Concurrent use with tetracyclines should be avoided due to reports of cases of pseudotumor cerebri with concurrent use. Clinically significant drug interactions have been reported when using vincristine with strong CYP450 3A4 inhibitors and inducers. Selected strong inhibitors of cytochrome P450 3A4 include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John[Single Quote]s wort. The use of these drugs should be avoided with vincristine. The clinical outcome and significance of CYP450 interactions with cyclophosphamide are less clear. CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution. Aprepitant also
interacts with CYP3A4 and should be used with caution with etoposide or vincristine chemotherapy. CISplatin should be used with caution with nephrotoxic drug. Aminoglycoside should be avoided or used with caution during or shortly after cisplatin administration and concomitant use with amphotericin B should probably also be avoided. Patients receiving CISplatin and other potentially ototoxic drugs such as aminoglycoside or loop diuretics concomitantly should be closely monitored for signs of ototoxicity. In patients receiving cisplatin and phenytoin or fosphenytoin, serum concentrations of phenytoin may decrease. Carbamazepine concentration may also decrease with concomitant use. Plasma levels of anticonvulsant agents should be monitored and doses adjusted during therapy with CISplatin. No other experimental therapy is permitted while on study. Adequate renal, liver and bone marrow function. All patients and/or their parents or legal guardians must sign a written informed consent. All institutional, FDA, and NCI requirements for human studies must be met. Spanish and Vietnamese speaking subjects are eligible to participate in this study using the Spanish and Vietnamese short form consent.