Inclusion Criteria:

• Patients with histologically proven supratentorial glioblastoma multiforme, gliosarcoma or anaplastic glioma will be eligible for the Phase I component of this protocol. Anaplastic gliomas include anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, or malignant glioma NOS. Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a malignant glioma is made. Only patients with histologically proven supratentorial glioblastoma multiforme or gliosarcoma will be eligible for the Phase II component.
• Patients must have shown unequivocal evidence for tumor recurrence or progression by MRI scan and should have failed radiation therapy. The scan done prior to study entry documenting progression will be reviewed by the treating physician to document changes in tumor dimension to confirm recurrence. Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis.
• Patients may have had up to 2 prior relapses provided the functional status and other eligibility criteria for enrollment are met.
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital.
• The baseline on-study MRI should be performed within 14 days (+ 3 working days) prior to registration and on a steroid dosage that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and the initiation of therapy (or at that time), a new baseline MRI is required. The same type of scan, i.e., MRI, must be used throughout the period of protocol treatment for tumor measurement.
• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as they have recovered from the effects of surgery. Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual measurable disease post-operatively, a MRI should be done no later than 96 hours in the immediate post-operative period or 4-6 weeks post-operatively.
• Patients must be 18 years old or older.
• Patients must have a Karnofsky performance status equal or greater than 60.
• Patients must have recovered from the toxic effects of prior therapy to < grade 2 non hematological or grade 2 or lesser hematological toxicity per CTC ver 3 (except deep vein thrombosis): 4 weeks from prior cytotoxic therapy and/or at least two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, cis-retinoic acid, etc. (radiosensitizer does not count). Patients who receive anticancer agents for non-therapeutic purposes unrelated to this study
• (9. continued) (such as presurgically for obtaining pharmacology data for the agent) will be eligible to enter the study provided they have recovered from the toxic effects of the agent if any. Because the trial is based on the hypothesis that the combination of agents used will be synergistic in their effects, and that HDAC inhibition will potentially overcome resistance to retinoids, prior treatment with cRA is allowed. Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
• Patients must have adequate bone marrow function (ANC = or > 1,500/mm^3 and platelet count of = or > 100,000/mm^3), adequate liver function (SGPT = or < 3 times normal and alkaline phosphatase = or < 2 times normal, bilirubin = or <1.5 mg/dl), adequate renal function (BUN and creatinine = or <1.5 times institutional normal) and normal serum amylase and lipase prior to starting therapy. Elevated cholesterol and triglycerides are not a contraindication to study enrollment, but should be managed as clinically appropriate.
• Patients must be willing and able to comply with the FDA mandated iPLEDGE program for treatment with isotretinoin (cRA). Patients must sign specific informed consents for treatment with cRA, as mandated by iPLEDGE guidelines. Women of childbearing potential must not be pregnant, must not be breast-feeding and must practice adequate contraception during and one month after participation in the study. Male patients on treatment with vorinostat must agree to use an adequate method of contraception for the duration of the study, and for 30 days after the last dose of study medication.
• Prior treatment with carboplatin is not allowed.

Exclusion Criteria:

• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix or bladder), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
• Patients must not have: a) active infection; b) disease that will obscure toxicity or dangerously alter drug metabolism, especially liver disease; c) serious intercurrent medical illness; d) prior recurrence with other HDAC inhibitors. However, patients who have received anticancer agents for non-therapeutic purposes (for eg., as part of a pharmacology study without therapeutic intent) will remain eligible; e) grade 2 or higher peripheral neuropathy.
• Pregnant and breast feeding women.
• Patients receiving valproic acid (VPA), an anticonvulsant drug with HDAC inhibitor properties, will be excluded, unless they are switched to an alternative agent prior to treatment initiation. No wash out period is required.
• Patients on previous treatment with carboplatin.
• Patients with a known allergy to any component of vorinostat, or a known allergy to carboplatin and/or isotretinoin.
• Patient must be able to tolerate the procedures required in this study including periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study. Inability to comply with protocol or study procedures (for example, an inability to swallow tablets) will be an exclusion criteria.