Intravesical anti-PD1 treatment for canine transitional cell carcinoma of the bladder

Bladder cancer (transitional cell carcinoma) is a relatively common form of cancer, especially in certain breeds of dog. In most cases, it is very difficult to treat with surgery given that tumor cells tend to float in the urine and seed several parts of the bladder. Also, this cancer does not respond well to chemotherapy, with only 20% of dogs having their tumor shrink following chemotherapy. In people and dogs, there is evidence that the immune system can kill bladder cancer cells. In humans, treatment with an antibody that blocks a protein called PD-1 induces tumor shrinkage in approximately 25% of humans with bladder cancer. Recently, a canine anti-PD-1 antibody has been developed that blocks the same protein in dogs. It is therefore possible that anti-PD-1 treatment in dogs will work to shrink canine bladder tumors. In humans, the anti-PD-1 treatment can be given intravenously or directly into the bladder. It is not entirely clear which method is more effective, and it is possible that direct administration to the bladder may be more likely to cause an anti-tumor response. The purpose of this study to is to evaluate the anti-tumor effects of a canine specific anti-PD-1 treatment in dogs with bladder cancer after direct administration into the bladder.

Inclusion Criteria

• Dogs diagnosed with transitional cell carcinoma of the bladder
• Dogs must be at least 1 year of age and body weight of 5 kg or higher.
• Adequate organ function as indicated by standard laboratory tests (complete blood count, serum biochemistry profile, urinalysis).
• ANC≥2000/μL and platelet count ≥ 100,000/μL
• Liver: Total bilirubin ≤ 1.5X the institutional upper limit of normal (ULN), ALT ≤ 3X ULN
• Renal: Serum creatinine ≤ 2X ULN
• ECOG performance score of 0-1
• Otherwise medically healthy with no underlying clinically significant cardiac, renal or hepatic disease.
• Informed written consent must be obtained

Exclusion Criteria

• Evidence of urethral or ureteral obstruction
• Evidence of metastatic disease to local lymph nodes, bone or lung
• Concurrent use of complementary or alternative medicines that in the opinion of the principal investigators would confound the interpretation of toxicities and/or antitumor activity of the study drug.
• Dogs with significant cardiovascular disease.
• Prior use of chemotherapy, radiation therapy, immunotherapy or any other treatment deemed by the PI to potentially interfere with study results.
• Any serious systemic disorder incompatible with the study (at the discretion of the principal investigators).

Client Benefits

The study will cover all costs associated with screening and treatment, and will cover costs associated with any potential side effects directly caused by the study procedures. However, the study will not cover costs associated with other medical conditions (i.e., ear infection, etc.).

Sample or Data Requirements

Your dog will also need to undergo tests (ultrasound of the abdomen and chest x-rays) to confirm that there is no obvious evidence of tumor spread beyond the bladder. Once officially enrolled, your dog will undergo general anesthesia and CT scan to measure the bladder tumor, followed by evaulation of the inside of the bladder using a fiberoptic scope (cystoscopy) to obtain 4 small biopsy samples. A urinary catheter will then be placed and the antibody will be instilled into the bladder where it will stay in place for 2 hours. The catheter will then be removed from the bladder. The CT scan/cystoscopy/biopsy/anti-PD-1 treatment will be repeated at 1 month and 2 months to monitor tumor size and immune changes in the tumor. Additionally, anti-PD-1 treatment will also take place 2 weeks after the first CT (Day 14) and 2 weeks after the second CT (Day 42), although this will be done with sedation rather than anesthesia as no CT scan or cystoscopy will happen on those visits. Lastly, we will take blood from your dog at each study visit (approximately 1.5 tablespoons) to monitor routine blood values and to collect cells that will help us determine how the immune response is changing. Your dog will not need to stay overnight in the hospital except after the first treatment so that we can take a final blood sample 24 hours after the first treatment.