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

Sponsor

Cedars-Sinai Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT02279992

Collaborator

(none)

Enrollment

Location

Arms

46.5

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Glioma Brain Neoplasms Brain Metastasis	Drug: Vardenafil Drug: Carboplatin	Early Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

7 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 27, 2012

Actual Primary Completion Date :

Oct 13, 2013

Actual Study Completion Date :

Feb 11, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vardenafil + Carboplatin 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 Other Names: Levitra® Phospodiesterase-V Inhibitor Drug: Carboplatin Other Names: Paraplatin®
Active Comparator: Carboplatin Alone Carboplatin (Paraplatin®) 100 mg IV administered over 30 minutes at the start of craniotomy	Drug: Carboplatin Other Names: Paraplatin®

Arm

Intervention/Treatment

Experimental: Vardenafil + Carboplatin

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

Other Names:

Levitra®

Phospodiesterase-V Inhibitor

Drug: Carboplatin

Other Names:

Paraplatin®

Active Comparator: Carboplatin Alone

Carboplatin (Paraplatin®) 100 mg IV administered over 30 minutes at the start of craniotomy

Drug: Carboplatin

Other Names:

Paraplatin®

Outcome Measures

Primary Outcome Measures

Concentration of intratumoral carboplatin in tumor tissue and serum samples [At the time of tumor resection]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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