NCT01324115

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

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
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	NG-nitro-L-arginine
OTHER	laboratory biomarker analysis
OTHER	pharmacological study
PROCEDURE	computed tomography
PROCEDURE	dynamic contrast-enhanced magnetic resonance imaging

Timeline

• Start date: 2011-04-01
• Primary completion: 2012-09-01
• Completion: 2012-09-01
• First posted: 2011-03-28
• Last updated: 2015-03-05

Locations

1 site across 1 country: United Kingdom