Phase I Evaluation of Gold Nanorods in Dogs with Solid Tumors

Purpose

The goal of this study is to determine the anti-tumor activity of gold nanorods against solid tumors in dogs

Background

The use of hyperthermia (heat) to treat cancer is well-established including radiofrequency ablation, laser-induced photodynamic therapy, and ultrasound ablation.  Gold nanorods (NRs), represent a class of metallic nanoparticles that may be synthesized in bulk, have broadly tunable plasmon resonance, and exhibit absorption coefficients much higher than conventional drugs typically used for photodynamic therapy.  Coating these nanorods with polyethyleneglycol polymers alongside visible- and NIR-absorbing molecules results in Surface-Enhanced, Resonant Raman Scattering (SERRS) resulting in enhanced activity.  These SERS-coded NRs are highly stable, are detectable down to extremely low concentrations, and limited activity in the laboratory dish. In vivo, SERS-coded nanorods are trapped in tumor blood vessels following intravenous injection permitting the heating of the nanorods to high temperatures within the tumor using an externally applied NIR diode laser. This approach has recently been successfully used to treat tumors in mouse models of cancer without evidence of systemic side effects.  This clinical trial is the first use gold nanorods in dogs with solid tumors.  The objectives of the protocol are:

  1. To assess the clinical effects of gold nanorods administered intravenously once to dogs with solid tumors.
  2. To assess the ability of gold nanorods to induce objective tumor responses (tumor shrinkage) in dogs with solid tumors following treatment with a NIR diode laser.
  3. To evaluate the microscopic (histopathologic) effects of gold nanorod/NIR diode laser treatment of solid tumors in dogs. 

Inclusion criteria

To qualify for enrollment in this study, dogs must have:

  • Histologically confirmed solid tumor (preferably soft tissue sarcoma, however other sarcomas or carcinomas can be enrolled)
  • Age > 1 year
  • A tumor amenable to repeat biopsy and must be located on the external part of the body
  • A life expectancy of at least 6 weeks
  • Not received chemotherapy (including prednisone) or radiation within 3 weeks of study entry and must have recovered from any side effects
  • At least 3 weeks apart from any major surgical procedure
  • No evidence of metastatic disease
  • At least 2 weeks apart from other investigational drug

Study Design

Nine dogs with solid tumors amenable to repeat biopsy that have failed conventional therapy or for which there is no therapeutic alternative or for which conventional therapy is not desired by the owner will be entered into the study.  Following appropriate staging tests (CBC, chemistry panel, and thoracic radiographs) to determine patient eligibility, a baseline biopsy will then be obtained, a portion of which will be placed in formalin for histopathologic analysis, and a second portion of which will be flash frozen for biochemical evaluation.   Dogs will be administered gold nanorods at a dose of 25 mg/kg.  This dose is based on clinical evaluation of gold nanorods in normal beagle dogs in which doses up to 32 mg/kg were given with no evidence of any adverse events.   Approximately 72 hours post nanorod injection, dogs will undergo NIR diode laser treatment until the tumor has been heated to approximately 40C for 1-2 minutes; the entire process is expected to take approximately 5 minutes.  Sedation will be administered to allow laser application without patient movement.  Dogs will be evaluated 7 days following treatment and on day 14 after treatment, the dog will undergo surgical excision of any remaining tumor.  If this is not possible, a second tumor biopsy will be performed to assess the extent of tumor death.  

Client Compensation

  • The study will cover all costs associated with visits, biopsy, bloodwork and procedures
  • After the study is completed, the client will receive $1000 to be used toward surgery for removal of the remaining tumor, or other treatments if the tumor is not amenable to surgical resection.

Client Cost

  • Owner is responsible for the initial office visit plus $25/visit and any additional costs that arise from prescribed medications, and the treatment of potential complications during the study

Contact Information

 Nicole Stingle or Tamra Mathie at clinicaltrials [at] cvm [dot] osu [dot] edu