Pilot Study of Vardenafil and Carboplatin in Patients With Gliomas and Brain Metastases

Twenty patients (10 pts with recurrent malignant glioma and 10 pts with metastatic brain
tumor) will be randomly assigned to receive either a phosphodiesterase-V inhibitor
(vardenafil) followed by carboplatin or carboplatin alone. All patients will have tumor
resection performed from 2 to 6 hours after administration of carboplatin. Using high
performance liquid chromatographic (HPLC) or ELISA methodology, carboplatin levels will be
determined from both serum and resected tumor tissue. Patients will be followed for four
weeks after craniotomy for toxicity associated with the administration of carboplatin and a
phosphodiesterase-V inhibitor plus carboplatin.

These data will provide quantitative measures of intratumoral carboplatin levels with and
without alteration of blood/tumor barrier (BTB) permeability with vardenafil.

Inclusion Criteria:

- Patients with recurrent malignant glioma or metastatic brain cancer requiring
craniotomy for gross total resection, subtotal resection or biopsy

- Previously histopathologically proven glioma or radiographic appearance of metastatic
lesion with a primary neoplasm that is known to metastasize to the brain

- Patients must have a Karnofsky performance status ≥ 60% (i.e. the patient must be
able to care for himself/herself with occasional help from others)

- Patients must have normal hematologic, renal and liver function (i.e. Hemoglobin >10
gm/dl, Absolute neutrophil count ≥ 1500/mm3, Platelets ≥ 100,000/mm3, creatinine ≤
1.5 mg/dl or Cr Clearance ≥ 60 mL/min, total bilirubin ≤ 1.5 mg/dl, transaminases ≤ 4
times above the upper limits of the institutional normal.

- Patients must be able to provide written informed consent

Exclusion Criteria:

- Patients with serious concurrent infection or medical illness, which would jeopardize
the ability of the patient to receive the treatment outlined in this protocol with
reasonable safety

- Patients who are pregnant or breast-feeding

- Patients receiving concurrent therapy for their tumor (i.e. chemotherapeutics or
investigational agents)

- Allergy to 5HT-(3) receptor antagonist including tropisetron, ondansetron

- Patients on enzyme-inducing anticonvulsants (Dilantin, Tegretol, Phenobarbital)

- Patients with unstable angina or serious cardiovascular disease

- Known HIV positivity or AIDS-related illness

- History of allergic reaction to platinum compounds or mannitol

- Medical conditions requiring the use of oral nitrates

- Patients on alpha-1 adrenergic blockers