Carboplatin in Treating Patients With Recurrent High-Grade Gliomas

PRIMARY OBJECTIVES:

I. Establish the maximum tolerated dose and define the toxicity profile of carboplatin delivered intracerebrally via convection enhanced delivery (CED) for patients with high grade glial neoplasms.

SECONDARY OBJECTIVES:

I. Examine the efficacy as defined by six-month progression free survival (PFS), median progression free survival, overall survival, and the radiographic response rate.

II. Evaluate the drug distribution.

OUTLINE: This is a phase I, dose-escalation study.

Patients undergo craniotomy and then receive carboplatin intracerebrally via convection-enhanced delivery (CED) over 72 hours.

Inclusion criteria

• Patients must have progressive disease for which craniotomy and tumor resection is recommended as treatment
• Patients must sign a consent form indicating that they are aware of the investigational nature of the study; the informed consent form will indicate that the patient has been made aware of all other appropriate therapies
• Patients with histologically confirmed grade III or IV astrocytoma, oligoastrocytoma, and oligodendroglioma who are at first or second recurrence
• Patients require an initial diagnosis of a malignant glioma as outlined in the inclusion criteria which must be confirmed at the treating facility
• Patients must have unequivocal evidence of tumor progression by magnetic resonance imaging (MRI) performed no longer than 28 days prior to study registration
• Patients must have pathologically confirmed recurrence at the time of catheter placement
• Patients must be on a stable or decreasing dexamethasone dosage for at least 1 week prior to baseline MRI
• Patients must have been treated previously with radiation therapy and treatment must have been completed at least 8 weeks prior to surgery for catheter implantation
• Last dose of cytotoxic chemotherapy must have been at least 4 weeks (6 weeks for nitrosoureas) prior to catheter placement; patients are eligible if they received bevacizumab or other anti-vascular endothelial growth factor (VEGF) therapies, although the most recent dose must be at least 6 weeks prior to catheter placement
• Patients previously treated with stereotactic radiosurgery, stereotactic radiotherapy, brachytherapy, Gliadel wafers or other intratumoral chemotherapy are eligible
• Patients must have recovered from all prior therapy
• Patients must have a life expectancy of >= 3 months and a Karnofsky performance status >= 60 Leukocytes >= 3,000/mcL Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Hemoglobin >= 9 g/dL Serum calcium =< 12.0 mg/dL Total serum bilirubin < institutional upper limit of normal (ULN) Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN Creatinine < 1.5 X institutional ULN
• Women of child bearing years must have a negative pregnancy test (serum or urine) within 1 week of study entry; men and women of reproductive potential must agree to use an effective contraceptive method including one of the following: surgical sterilization (tubal ligation for women or vasectomy for men); approved hormonal contraceptives (such as birth control pills, Depo-Provera or Lupron Depro); barrier methods (such as condom or diaphragm) used with a spermicide cream or an intrauterine device (IUD)
• Patient or designated individuals with durable medical power of attorney must give written informed consent prior to any study-specific procedures being implemented
• Both men and women and members of all races and ethnic groups are eligible for this trial

Exclusion criteria

• Patients with infratentorial, multifocal, or pathologically confirmed cerebrospinal fluid (CSF) disseminated tumor
• Patients that have been treated with > 3 prior chemotherapy regimens
• Pregnant or lactating women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception
• Patients who have a history of bleeding disorders including congenital or acquired coagulopathies
• Known acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition or other acquired or congenital disorder of the immune system
• Patients with unstable or serious concurrent illness including, but not limited to, ongoing or active infections requiring IV antibiotics or psychiatric illness/social situations that would limit compliance with study requirements are ineligible; (if patient has a stable chronic infection requiring oral antibiotics, the patient may be treated at the investigators discretion; however a clinical note must include the justification regarding the safety of treating the patient)
• Patients who have received any other investigational agent in a 28-day period prior to enrollment in this study
• Patients whose tumors are located less than 2 cm from the ventricles
• Patients taking greater than 12 mg daily of dexamethasone
• Prior invasive malignancy that is not low-grade glioma, glioblastoma or gliosarcoma (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless the patient has been disease free and off therapy for that disease for a minimum of 3 years