NG-Nitro-L-Arginine in Treating Patients With Advanced Solid Tumors
- Conditions
- Unspecified Adult Solid Tumor, Protocol Specific
- Registration Number
- NCT01324115
- Lead Sponsor
- Cancer Research UK
- Brief 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Dose-limiting toxicities (DLT) and/or subsequent maximum dose Dose at which there is no additional differential effect of L-NNA on the tumor vasculature as measured by dynamic contrast-enhanced computed tomography (DCE-CT) Pharmacokinetic (predominantly AUC-dependent specific vascular effects) dependent effects (duration and magnitude of effect on blood flow/volume) in the tumor tissue compared to renal tissue using data from volumetric assessments via DCE-CT
- Secondary Outcome Measures
Name Time Method Effect on tumor blood perfusion using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with additional blood oxygen level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI) sequences Causality of each adverse event to L-NNA and severity grade according to NCI CTCAE Version 4.02 Tertiary Outcome(s) - Measurement of L-NNA concentrations in plasma samples Measurement of serum biomarker concentrations, osteopontin, and vascular endothelial growth factor (VEGF-A) Measurement of NOS concentrations in circulating blood (cyclic guanine monophosphate analysis) Measurement of iNOS and eNOS expression levels in pre-treatment tumor biopsy samples (where available)
Trial Locations
- Locations (1)
Mount Vernon Cancer Centre at Mount Vernon Hospital
🇬🇧Northwood, England, United Kingdom