Urinary Bladder Cancer Trial

Urinary bladder cancer, medically termed as invasive urothelial carcinoma (InvUC) or transitional cell carcinoma (TCC), is a serious form of cancer. It can lead to blockage of urine flow and secondary organ dysfunction caused by the spread of cancer. Although most dogs with TCC initially respond favorably to treatment, the cancer often becomes resistant to treatment over time and recurs, or grows back again. This is why we are studying ways to improve bladder cancer treatment. This cancer is an ongoing focus of research in the Werling Comparative Oncology Research Center.

Any new information we learn from dogs with TCC will help current and future dogs that develop this type of cancer. Additionally, canine TCC is very similar to muscle invasive bladder cancer in people. Our studies have been able to translate to human research efforts to help those affected by this type of cancer as well.

One study is open for dogs with TCC: All of our trials are approved by the Purdue Animal Care and Use Committee.

Immunotherapy Trial for Dogs with Urinary Bladder Cancer

Principal Investigator

Dr. Deborah Knapp, Distinguished Professor of Comparative Oncology; Director, Evan and Sue Ann Werling Comparative Oncology Research Center

Background

The goal of this study is to evaluate a new immunotherapy approach in dogs with urinary bladder cancer, specifically invasive urothelial carcinoma (InvUC), also called transitional cell carcinoma (TCC). We just completed a study at Purdue University to determine the safety, antitumor effects, and immunologic effects of a new immunotherapy drug (cPD-L1 mAb) for dogs with InvUC. The results of this trial were very favorable. With the information we learned from the initial trial, we are now building on that to combine the cPD-L1 mAb with standard of care drugs for InvUC with the expectation that the antitumor effects will be even greater.

Our immunotherapy drug, the cPD-L1 mAb, is classified as an "immune checkpoint inhibitor." Immune checkpoint inhibitors have had dramatic anticancer effects in human cancer patients. Jimmy Carter, for example, benefited from a drug in this class to eradicate his metastatic melanoma several years ago. In recent years, in people immune checkpoint inhibitors are being administered in combination with other therapies to get the best outcome for the patients. We anticipate that the combination therapy in dogs will prove to have excellent efficacy against InvUC.

The advantages to participating in the clinical trial are that (1) each dog will gain access to a new treatment regimen that is expected to fight their cancer, (2) at the same time we will learn important information to help other dogs and humans, and (3) the treatment is provided to the dog at a discounted cost compared to other treatment regimens.

Eligibility for Dogs to Participate in the Study

Good general health
Serum creatinine (a measure of kidney function) of 2.0 mg/dl or less
Biopsy-confirmed diagnosis of InvUC or the presence of a urinary bladder and/or urethral mass with a strong suspicion for InvUC, with the diagnosis to be confirmed during the study
No prior radiation therapy or chemotherapy
Previous use of nonsteroidal anti-inflammatory drugs (NSAIDs) will be allowed, but a wash out period will be required. In other words, the dog has to be off of the NSAID for 5-14 days (depending on which NSAID they received) before enrolling in the trial.
The dogs cannot be receiving Librela ®or Cytopoint ® injections
No current supplements including vitamins, herbs, CBD products, “immune health” products, or other supplements are allowed. Supplements are not allowed during the study because they can potentially reduce the efficacy of the therapy and increase risk of side effects. A 2-week washout is required between the last supplements given and enrollment into the study.

What is Involved for the Dog/Dog Owner

To start participating in the study, your dog will have a 2-day visit at the Purdue University Veterinary Hospital to enroll in the study. Initial tests to confirm your pet’s health status and extent of cancer are performed on day one. These tests include blood and urine tests, and imaging with x-rays and ultrasound. On day two, a urinary bladder scoping (cystoscopy) will be performed to collect a sample of the tumor tissue to confirm the diagnosis, and analyze immune cells. Cystoscopy is performed under general anesthesia.
After a definitive diagnosis is confirmed, your dog will then return to Purdue to start treatment. Your dog will be randomized to one of three treatment arms, with each arm including three drugs. The difference between the arms is the sequence in which the three drugs are given. The sequence is expected to be important, and the trial will help sort out which sequence is most effective. There will not be a placebo arm for this study.
The first arm of the study begins with standard of care drugs (vinblastine and deracoxib) for InvUC. Vinblastine is an intravenous (IV) chemotherapy that is administered every 2 weeks. Deracoxib is an NSAID that will be administered by mouth daily at home. The immunotherapy (cPD-L1 antibody) is added later in this treatment arm.
The second arm of the study combines the standard of care with immunotherapy, cPD-L1antibody together up front. For this arm, the dogs will receive immunotherapy every 2 weeks IV and then will receive vinblastine IV 3 hours after the administration of the immunotherapy. Dogs will also receive deracoxib at home daily.
The third arm of the study combines vinblastine with the immunotherapy and is administered every 2 weeks IV. Deracoxib will be added to the treatment protocol later in this arm.
For the first dose of the immunotherapy, the dog will be required to stay overnight after the initial treatment for observation and to donate small blood samples throughout the first 24 hours.
After the initial dose of the cPD-L1, the dogs will have blood samples obtained at each odd numbered dose, i.e after dose 3, 5, 7, etc.
All IV treatments are required to be performed at the Purdue University Veterinary Hospital.
A second scope will be requested 2 months after initiating treatment, in 10 dogs from each arm. This will allow us to track the immune cells in the tumor mass. This is expected to help us better understand how to make immunotherapy work better. This visit will take 2-3 days at the Purdue University Veterinary Hospital.
If your dog’s cancer begins to grow with treatment or if they develop bothersome side effects that do not lessen with dose adjustments, they will go “off study” and could receive other treatments. After going off study the owner resumes responsibility to pay full price for the recommended treatment.
We hope each dog lives a long time with a good quality of life. Ultimately, we realized that each dog will reach the end of their life eventually. The pet owner is asked to consent to necropsy (autopsy) when their dog passes, whether the death is due to the cancer or an unrelated condition. Examining cancer tissues is extremely beneficial in helping us to understand how the drugs work at the molecular level, how the immune system is affected, and how we can make our treatments work even better.

Financial Support

The pet owner is required to pay $300 per visit to defray the expenses related to the study treatment and diagnostic tests to monitor the cancer response that are performed at the Purdue University Veterinary Hospital.
The remainder of the expenses incurred at the Purdue University Veterinary Hospital including those related to the cancer treatment, monitoring the response to treatment, and managing any potential side effects if they occur will be covered by the study.
It is expected that all treatments and monitoring be performed at the Purdue University Veterinary Hospital. Any visit to the referring veterinarian, should those occur, must be paid for by the dog owner. Similarly, any veterinary care that is not related to the InvUC or the cancer treatment must be covered by the owner.

Trial Status

ACTIVELY RECRUITING

How can my dog participate?

Pet owners and veterinarians that are interested in the trial, who would like more information, or have questions are asked to contact our clinical trials technician, Lindsey Fourez at lfourez@purdue.edu or 765-494-1130.
We recommend scheduling an appointment for evaluation with our team at Purdue. This visit will allow us to determine if the trial is the best option for your dog and if eligibility requirements are met. If we determine that the trials is not the best option, we will happily assist with other treatment options.

Questions

Call the Purdue University Veterinary Hospital at 765-494-1107 to schedule an appointment.

Immunotherapy Trial with a Therapeutic Canine PD-L1 Monoclonal Antibody in Dogs

Principal Investigator

Dr. Deborah Knapp, Distinguished Professor of Comparative Oncology; Dolores L. McCall Professor of Comparative Oncology; Director, Evan and Sue Ann Werling Comparative Oncology Research Center

Background

The goal of this study is to determine the anticancer effects of a new immunotherapy drug in dogs with TCC. This immunotherapy is classified as an "immune checkpoint inhibitor." Immune checkpoint inhibitors have had dramatic anticancer effects in human cancer patients. Jimmy Carter, for example, benefited from a drug in this class to eradicate his metastatic melanoma several years ago. We anticipate that immune checkpoint inhibitors can help dogs with cancer as well.

The immune checkpoint inhibitor we are evaluating is a monoclonal antibody to a protein called PD-L1. It is given by an intravenous infusion at 2-week intervals. This canine PD-L1 antibody, which we will refer to as the “cPD-L1 mAb”, was developed at Purdue University.

The advantages of trial participation is that the pet will receive a new drug that is expected to help fight thier cancer at a discounted cost compared to other therapies.

Eligibility For Dogs to Participate in the Study

Good general health and a serum creatinine (a measure of kidney function) <2.0 mg/dl.
Biopsy-confirmed diagnosis of TCC or the presence of a bladder and/or urethral mass with strong suspicion for TCC with the diagnosis to be confirmed during the study.
No prior radiation therapy is allowed.
A “washout” period is required if the dog has received prior chemotherapy to allow time for the drug to leave the dog’s body.
Previous use of nonsteroidal anti-inflammatory drugs (NSAIDs) will be allowed in selected circumstances.
No current supplements including vitamins, herbs, CBD products, “immune health” products, or other supplements are allowed. Supplements are not allowed during the trial because these can reduce the efficacy of the therapy and increase risk of side effects. A 2-week washout period is required between the last supplements given and enrollment in the trial.

What is involved for the dog/dog owner?

To start participating in the trial, the dog will have a 2-day visit at the Purdue Veterinary Hospital to enroll in the trial and have initial tests to confirm the dog’s health status and extent of the cancer. The tests will include blood and urine tests, imaging with x-rays and ultrasound, and a bladder scoping (cystoscopy) to collect small samples of the cancer to confirm the diagnosis and assess immune cells in the cancer. Cystoscopy is performed under general anesthesia.
The dog will return the next week to start the cPD-L1 mAb treatment. The dog will stay a full day and overnight in the hospital for the first treatment. The first 6 dogs enrolled will also need to provide blood samples at 1, 2, 3, and 7 days after the first treatment.
The cPD-L1 mAb is given as an intravenous infusion, and treatments will continue at 2-week intervals. Each treatment will require the dog to be in the hospital all day.
At the time of the third treatment, the cystoscopy will be repeated. This visit will take 2-3 days at the Purdue Veterinary Hospital.
There is no limit to the number of cPD-L1 mAb doses the dog can receive. As long as the cancer is controlled and the pet feels well they can continue to receive the treatments.
If the dog’s cancer begins to grow again with the cPD-L1 mAb treatment or if the dog develops major side effects, they would go “off study” and could receive other types of therapy. After going off study, the owner resumes responsibility to pay full price for the recommended therapies.
We hope each dog will live a long time with a good quality of life. Ultimately, we realize each dog will reach the end of their life eventually. The dog owner is asked to give consent to a necropsy when their dog passes, whether the death is due to the cancer or an unrelated condition. Examining the cancer tissues is extremely beneficial in helping us understand how this drug worked at the molecular level, how it affected the immune system, and how we can make it work even better.

Financial Support

The dog owner is required to pay $300 per month to defray the expenses related to the study treatment and diagnostic tests to monitor the cancer response that are performed at Purdue.
The remainder of the expenses incurred at Purdue including those related to the treatment, monitoring the response to treatment, and managing any potential side effects if they occur will be covered by Purdue.
It is expected that the treatments and monitoring will be performed at Purdue. Any visits to the regular veterinarian, should those occur, must be paid for by the dog owner. Similarly, any veterinary care that is not related to the cancer or the cancer treatment must be covered by the dog owner.

Trial Status

COMPLETED

CDK9 Inhibitor Trial in Dogs

The goal of this study is to determine the antitumor effects of a new drug to treat TCC. Briefly, veterinarians in the WCORC work closely with scientists in the Purdue Institute for Cancer Research (PICR), an organization on campus focused on eradicating human cancer. One of the PICR scientists, Dr. Majid Kazemian, has used a unique type of computer modeling to learn new ways to attack cancer at the molecular level. His work has identified a new drug which is expected to cause remission in patients with TCC. The new drug is called enitociclib and it is a type of drug called a CDK9 inhibitor. Our goal is to determine how effective this drug is in dogs with TCC. This is the first study of its kind as this type of medication (CDK9 inhibitor) is a brand new approach to treating TCC.

The advantages for the pet participating in the trial is that they will receive a new drug that is expected to work well against TCC and at a lower cost than other treatments. Simultaneously, our team will learn important information about how to better treat TCC in dogs and in humans.

Principal Investigator

Dr. Deborah Knapp, Distinguished Professor of Comparative Oncology; Dolores L. McCall Professor of Comparative Oncology; Director, Evan and Sue Ann Werling Comparative Oncology Research Center

Background

The treatment for dogs with TCC has improved over several years, but better therapy approaches are still needed.
This trial will help us determine how well the new treatment strategy will work.
This new trial is for dogs with TCC in the bladder and/or the urethra, with or without cancer in other locations.
The new drug, enitociclib, is given by an intravenous treatment at weekly intervals. The dogs must come to Purdue for each treatment.
To determine how well the drug is working at the molecular level, a sample of the TCC tissue will be collected through a scope before and after a month of treatment.
Because invasive TCC in canines is so similar to muscle invasive bladder cancer in humans, this new knowledge will help dogs and people facing invasive TCC.

Eligibility for Dogs to Participate in the Study

Good general health of the dog, serum creatinine (a measure of kidney function) <2.0 mg/dl, and serum alanine amino transferase (a liver chemical) < 138 U/L.
Confirmed diagnosis of TCC or the presence of a bladder and/or urethral mass with strong suspicion for TCC with the diagnosis to be confirmed during the study.
No prior radiation therapy is allowed.
A “washout” period is required if the dog has received prior chemotherapy to allow time for the drug to eliminate from the dog’s body.
Previous use of nonsteroidal anti-inflammatory drugs (NSAIDs) will be allowed in selected circumstances.
No current supplements including vitamins, herbs, CBD products, “immune health” products, or other supplements are allowed. Supplements are not allowed during the trial because these can reduce the efficacy of the therapy or make the dog sick.

What is involved for the dog/dog owner?

At the beginning, the dog will have an extended, 2-day visit at the Purdue Veterinary Hospital to enroll in the trial. Diagnostic staging and blood tests will be done to determine the extent of the cancer. Then, a cystoscopy is performed to collect a sample, or biopsy, of the cancerous tissue.
Evaluation includes blood tests, ultrasound, x-rays, and cystoscopy. Cystoscopy is performed under general anesthesia.
The treatment involves an intravenous infusion given at weekly intervals. The first and fourth treatment will consist of an extended, 2-day visit at the hospital. For other treatment days will be considered outpatient, where the pet arrives that morning and will leave with the owner the same afternoon.
After the second visit, the dog will continue to receive the CDK9 inhibitor for as long as the cancer is controlled and if the dog feels well.
If the cancer begins to grow in the face of the CDK9 inhibitor treatment, then the pet can go "off study" and will be eligible for other therapies. The expenses for treatments given off study will have to be covered by the dog owner.
The new drug is expected to be well tolerated, but side effects such as low blood counts or stomach upset are possible. The drug dosage will be adjusted if these occur, or the dog can go off study and receive other therapies.
Although we hope each dog will live a long time with a good quality of life, we know each dog will reach the end of their life eventually. The dog owner is asked to allow a necropsy when their dog dies whether the death is due to cancer or some other condition. Examining the tumor tissues after the dog has died is beneficial in helping us understand how the new drug worked at the molecular/cell signaling level, and how to make it work even better.

Financial Support

All costs associated with the trial, including diagnostics, treatments, and follow-up care will be completely covered for services provided at the Purdue University Veterinary Hospital while your pet is actively enrolled and recieving CDK9 inhibitor treatment.
It is expected that the treatments and monitoring will be performed at Purdue. Any visits to the regular veterinarian, should those occur, must be paid for by the dog owner. Similarly, any veterinary care that is not related to the cancer or the cancer treatment must be covered by the dog owner.

Trial Status

COMPLETED