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Inhibition of JAK2/STAT3 signaling by toceranib phosphate (Palladia)
The primary objective of this clinical trial is to determine whether Palladia is capable of inhibiting JAK activity in tumors in dogs.
Toceranib (Palladia) is an orally administered anti-cancer drug that works by blocking the signaling of several cell receptors involved in both tumor growth and new blood vessel formation. Since its approval in 2009, Palladia has been used to treat a variety of solid tumors in dogs. Activity has now been demonstrated in several forms of carcinomas, including nasal, squamous cell, thyroid and anal gland anal sac tumors. The basis for this activity is not entirely known, but a recent study indicates that Palladia may be inhibiting a protein called JAK2 in tumors, particularly carcinomas, and may be responsible for some of the anti-tumor activity observed in these tumors. We investigated whether Palladia could inhibit phosphorylation of JAK2 in canine tumor cell lines and found that it does inhibit this protein in the laboratory setting. These data support the notion that Palladia may exert some of its biologic activity in solid tumors via combined inhibition of JAK family members.
To qualify for enrollment in this study, dogs must have:
- Histologic or cytologic or histologic diagnosis of squamous cell carcinoma (biopsy or needle aspirate).
- Measureable disease must be present.
- Generally feeling well (i.e. eating, drinking, ambulating on their own, etc.)
- Not received any prior chemotherapy or radiation therapy.
- Adequate organ function as indicated by standard laboratory tests (complete blood count, serum biochemistry profile, urinalysis).
To accomplish this, we will evaluate JAK phosphorylation before and after Palladia treatment. Eligible dogs with squamous cell carcinoma will undergo a tumor biopsy prior to Palladia therapy. Palladia will then be administered every other day at home for 7 days (4 doses), at which time a second biopsy will be performed on Day 7. Should a tumor response be noted (stable disease or tumor shrinkage) during the 7 day period, Palladia (provided at no charge for 6 months) can be continued until a response is no longer noted.
The costs associated with obtaining the two biopsies and the Palladia treatment will be covered by the clinical trial, all other costs will be at the responsibility of the owner. In addition should a tumor response be noted Palladia will be provided for 6 months post study completion at no charge until a response is no longer noted or the 6 months are completed. A onetime $500 credit will be given at the completion of the study to be used at The Ohio State University Veterinary Medical Center for further treatments. All other costs are at the responsibility of the owner.
Dr. Cheryl London