NG-Nitro-L-Arginine in Treating Patients With Advanced Solid Tumors

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title: A Phase I Trial of NG-Nitro-L-Arginine (L-NNA), a Nitric Oxide Synthase Inhibitor, Given as a Single Intravenous Infusion Over 10 Minutes in Patients With Advanced Solid Tumors

Status Terminated

Clinical Trial Summary

RATIONALE: NG-nitro-L-arginine may stop the growth of tumor cells by disrupting blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and best dose of NG-nitro-L-arginine in treating patients with advanced solid tumors.

Clinical Trial Description

OBJECTIVES:

Primary

• To determine if there is a differential effect of NG-nitro-L-arginine (L-NNA) on tumor and normal tissue vasculature (blood flow/volume) in patients with advanced solid tumors in order to propose a safe recommended dose range for further evaluation.

Secondary

• To determine the correlation between plasma concentration of L-NNA and toxicity and vascular effects.

• To further determine the effects of nitric oxide synthase (NOS) inhibition on tumor tissue vasculature.

• To determine the pharmacokinetics of L-NNA.

• To determine the safety profile of L-NNA.

Tertiary

• To evaluate the potential pharmacodynamic effect of NOS inhibition on angiogenesis.

• To evaluate the effect of L-NNA on circulating NOS levels.

• To evaluate the correlation between expression levels of iNOS and eNOS and vasoconstrictive effects of L-NNA in tumor tissue (where available).

OUTLINE: This is a dose-escalation study.

Patients receive a single dose of NG-nitro-L-arginine (L-NNA) IV over 10 minutes on day 1. All patients undergo up to 6 dynamic contrast-enhanced computed tomography (DCE-CT).

Patients enrolled in the expanded cohort study undergo 4 additional scans of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as well as DCE-CT scans.

Blood samples are collected periodically for pharmacokinetic and biomarker studies. Samples are analyzed for L-NNA levels via a reverse-phase high performance liquid chromatography, NOS inhibition via cGMP analysis, and VEGF-A and osteopontin levels. Previously collected biopsy samples are analyzed for iNOS and eNOS expression.

After completion of study treatment and one week assessments, patients are followed up once a week for 28 days and then monthly thereafter (if required).

Peer Reviewed and Funded or Endorsed by Cancer Research UK. ;

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

• NCT number: NCT01324115
• Study type: Interventional
• Source: Cancer Research UK
• Status: Terminated
• Phase: Phase 1
• Start date: April 2011
• Completion date: September 2012