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

Study Overview
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Brief Summary
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This is a randomized pilot study to investigate the ability of a phosphodiesterase-V inhibitor (vardenafil) to increase the concentration of systemically delivered chemotherapy, carboplatin, in patients with recurrent malignant gliomas or metastatic brain cancer. This study will also determine the toxicity and tolerability of a phosphodiesterase-V inhibitor (vardenafil) in combination with intravenous carboplatin for patients with recurrent malignant gliomas or metastatic brain cancer.

Detailed Description
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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.

Official Title
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CSMC IIT: Pilot Study of Phosphodiesterase-V Inhibition to Increase Intratumoral Concentration of Carboplatin in Patients With Recurrent High Grade Gliomas and Brain Metastases

Conditions
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Glioma, Brain Neoplasms, Brain Metastasis

Intervention / Treatment
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* Drug: Vardenafil
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vardenafil + Carboplatin<br>Vardenafil (Levitra®) 20 mg oral administered 1 hour prior to start of craniotomy + Carboplatin (Paraplatin®) 100 mg IV administered over 30 minutes at the start of craniotomy | Drug: Vardenafil<br> <br> * Other names: Phospodiesterase-V Inhibitor;Drug: Carboplatin<br> <br> * Other names: Paraplatin®;|
| Active Comparator: Carboplatin Alone<br>Carboplatin (Paraplatin®) 100 mg IV administered over 30 minutes at the start of craniotomy | Drug: Carboplatin<br> <br> * Other names: Paraplatin®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of intratumoral carboplatin in tumor tissue and serum samples |  | At the time of tumor resection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of vardenafil in combination with carboplatin using common terminology criteria for adverse events (CTCAE) version 3.0 |  | From baseline to 1 month post-resection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant Glioma, Brain Neoplasms, Malignant, Brain metastasis