CSU Animal Cancer Center Clinical Trial

Patient Disease:
Malignant Histiocytosis (MH).

Study Name:
Combination liposomal clodronate and CCNU treatment for dogs with malignant histiocytosis.

Purpose of the Study:
Macrophages are immune cells that normally scavenge bacteria and clear a variety of substances (such as cell debris, bacteria, and foreign materials) from the body. Recent studies suggest that this cell type may actually play an important role in promoting tumor growth and spread (metastasis). Macrophages may also contribute to the ability of tumor cells to become resistant to chemotherapy. Therefore, we are investigating the effectiveness of a new compound that is designed to eliminate macrophages transiently from the body. Canine MH is thought to be a tumor arising from macrophages and we have found that canine MH cells are susceptible to liposomal clodronate in vitro (see below). The clodronate drug is administered after being encapsulated within liposomes, which are tiny, spherical particles that are widely used to deliver various drugs in the body. Bisphosphonates (the family of drugs to which clodronate belongs) have been used widely in the treatment of bone cancer metastases in people and dogs.

Studies in mice have indicated that treatment with liposomal clodronate can significantly inhibit tumor growth. A recently completed study in dogs with MH conducted by our group (Hafeman, et al; Cancer Immunol Immunoth, 2009) demonstrated that liposomal clodronate had anti-tumor activity when administered to dogs with MH. A second drug (CCNU) is commonly used in the treatment of dogs with MH and most of our MH patients receive CCNU treatment at some point in their treatment protocol. Recently, we treated two dogs with liposomal clodronate followed shortly by CCNU treatment. Both of these dogs experienced dramatic and sustained complete tumor regression, which we believe may be due to a positive interaction between the two drugs. Notably, both dogs had already been treated with CCNU and initially failed treatment. This suggests that treatment with liposomal clodronate may restore tumor responses to CCNU treatment. Therefore, the current clinical trial is designed to investigate whether this combination treatment is in fact more effective for dogs with MH than either drug alone.

Patient Entry Criteria:
Dogs with cytology or biopsy confirmed MH tumor of any site are eligible for this study. No prior treatment with CCNU is allowed, and washout periods from corticosteroids, other chemotherapy agents, and radiation therapy are required. Concurrent NSAID therapy is not permitted. Dogs with any serious underlying diseases, including renal disease, liver disease, autoimmune disease, and chronic infectious diseases, are however excluded from the study. Also, dogs with very large MH tumors may not be eligible for the study, at the discretion of the clinician.

Owner Responsibilities:
You are financially responsible for charges associated with staging tests to determine your pet's eligibility for enrollment in this study. You are expected to make and keep all appointments according to the study protocol. You must be committed to completing the entire protocol and follow-up examinations. Please do not hesitate to obtain additional information from your pet's oncology clinician if you do not understand something about the study or your pet's care and treatment.

Financial Incentives:
Once enrolled, the study will pay for the costs of study-related blood work, hospital fees and the costs of the liposomal clodronate and CCNU.

If you have further questions about any of our clinical trials, please complete an online consult request form below or call or Oncology Clinical Coordinator at (970) 297-4068.