Efficacy Evaluation of Implanted Agarose-Agarose Macrobeads Containing Mouse Renal Adenocarcinoma Cells in Dogs with Spontaneous Hemangiosarcoma (HSA).

Purpose

To determine the potential biologic activity of RENCA cancer-cell-containing macrobeads implanted in dogs with hemangiosarcoma (HSA) as compared to historical control animals.

Background

This clinical trial evaluates the safety and effectiveness of agarose-agarose macrobeads containing mouse renal carcinoma (RENCA) cells placed in the abdominal cavity in dogs with spontaneous splenic hemangiosarcoma (HSA). Despite aggressive chemotherapy, most patients with splenic HSA do not survive beyond 5-6 months. Therefore, new therapies are needed to treat this disease. One novel approach to treat cancer is immunotherapy, where the body’s own immune system is stimulated to kill the cancer cells. This can be done using a variety of agents including tumor vaccines, cytokines, and other approaches. Another new immunotherapy is the RENCA macrobeads. The Mouse Renal Adenocarcinoma Cells (RENCA) produces a variety of agents that may stimulate the immune system as well as agents that directly inhibit tumor growth. The study soponsor has developed a method to encapsulate these cells in agarose, an inert gel that allows the cells to survive and secrete factors that inhibit tumor growth, both in laboratory dishes and in animals. These secreted factors are small and can diffuse out of the agarose macrobead, while the mouse cells remain contained. Thus, the active factors are delivered directly to the patient.

The RENCA agarose-agarose macrobeads that are to be used for this clinical trial are composed of two concentric spherical agarose layers. The mouse RENCA cells are contained within the inner layer of agarose, and an outer layer of agarose covers the inner layer. The diameter of each macrobead is 6-8 mm (approximately ¼ of an inch). As previously discussed, the RENCA cells, although they proliferate in the inner layer of agarose, do not invade the outer layer of agarose or escape from an intact macrobead. In addition, cells from the host (dog) cannot enter into the macrobead. In case a macrobead placed into the patient’s abdomen will fracture, the Renca cells will be destroyed by the patients’ immune system. The macrobeads have been shown to produce the inhibitory compounds for at least 3 years in the tissue culture dish and 6 months in vivo in mouse animal studies.

In this clinical trial, the RENCA macrobeads will be placed in the abdominal cavity of dogs with HSA. Results from previous studies suggest the macrobeads will remain free (floating) in the abdominal cavity and will not become attached in the abdomen. A previous pilot study in dogs and cats with a variety of different cancers demonstrated that the macrobeads were safe when implanted in the abdominal cavity and clinical benefit was observed in some cases. Most importantly, these patients did not exhibit any obvious evidence of toxicity from the macrobeads. A similar study in humans was also not associated with any obvious evidence of toxicity. The purpose of this study is to evaluate the effectiveness of the RENCA macrobeads in prolonging survival in dogs with HSA.

To qualify for enrollment in this study, dogs must:

  • Have confirmed histologically proven abdominal (spleen, liver, etc) HSA that has been removed
  • Be a candidate for surgical implantation of the macrobeads
  • Have no evidence of tumor spread (metastasis).

Exclusion Criteria

  • Life expectancy of less than 3 months
  • Low platelet count
  • Any history of hypersensitivity reactions or determined allergy to mouse antigens
  • The presence or signs of major clotting abnormalities
  • Significantly compromised liver function
  • Radiation/chemotherapy within 3 weeks of baseline evaluation
  • Evidence of metastasis on screening for study entry

Study Design/Treatment

  • Day-7-0 Baseline blood collection, Chest Radiographs, abdominal Ultrasound
  • Day 0 Implantation, stays overnight
  • Day 1-2 blood collection goes home with owner daily log.
  • Day 12 blood collection, abdominal ultrasound
  • Day 30 Blood collection, abdominal ultrasound
  • Day 60 Blood collection, abdominal ultrasound, Chest Radiographs Cycle continues every month and Owner daily logs must be brought back at each visit.

Client Compensation

All costs related to the study once the patient is enrolled (implantation, bloodwork, radiographs, etc.), with the exception of the Hospital Chart fee, are covered by the study. If there are any adverse events after implantation, the study will cover the cost of treatment.

Contact Information

For more information on this trial, please contact:

Dr. Cheryl London
clinicaltrials [at] cvm [dot] osu [dot] edu