Bladder cancer clinical trials for dogs.

ANY CLINIC (but reporting results to UC Davis)
Study: Carboplatin/Piroxicam versus Mitoxantrone/Piroxicam
Location: University of California Veterinary Hospital Davis, CA
Phone: 530.752.0125
www.vetmed.ucdavis.edu/vmth/small_animal/oncology/studies.cfm

Eligibility: Canine pets with TCC (Transitional Cell Carcinoma) of the bladder.

Purpose: To compare two chemotherapy regimens: carboplatin plus piroxicam versus mitoxantrone plus piroxicam.

Summary: The clinical trial is comparing the use of different drugs in different combinations to provide a more effective way
of treating various diseases. This trial can be conducted at any clinic provided that the clinic is able to administer
chemotherapy and can report results to UC Davis. If you would like to participate in this study, have your veterinarian call
UC Davis at 530.752.1393. Your local veterinarian would call UC Davis to 'pull an envelope'. Each envelope is randomly
pulled comparing the different treatment. There is no placebo and it is 'open-label' meaning you will know exactly what drug
your pet is receiving.

Requirements and incentives: There is no financial incentive.

CALIFORNIA
Study: Quantitative Contrast Ultrasound Imaging of Canine Bladder Tumors
Location: University of California Veterinary Hospital Davis, CA
Phone: 530.752.0125
www.vetmed.ucdavis.edu/vmth/small_animal/oncology/studies.cfm

Eligibility: All dogs must be examined by a VMTH oncology or radiation oncology service veterinarian, and require the
following baseline evaluations at the owners expense before a dog can be considered for enrollment in the trial:

Confirmed diagnosis
Physical examination with weight recorded
CBC, Chemistry Panel and Urinalysis All within two weeks of enrollment (referring blood work is acceptable as long as
it was ran at a commercial lab)

Baseline Evaluation for Eligibility:

Histologically or cytologically confirmed diagnosis of transitional cell carcinoma with no previous treatment
Identifiable bladder mass
No evidence of severe cardiac disease
Informed owner consent

Purpose: The purpose of this study is to assess a novel ultrasound technique for its ability to predict whether a dog is
responding to chemotherapy early in the course of treatment.

Summary: Bladder tumors are a relatively common type of cancer in dogs. They often are large enough or occur in a bad
enough location that surgical removal is not possible. Thus, chemotherapy is the standard treatment with most dogs living
for 6-12 months after diagnosis. Currently, there is no concensus regarding which chemotherapy results in the longest
overall survival. Some dogs may have a better response to one type of chemotherapy while others respond better to a
different type. The purpose of this study is to assess a novel ultrasound technique for its ability to predict whether a dog is
responding to chemotherapy early in the course of treatment. This technique involves the intravenous injection of a contrast
agent that allows for visualization of blood vessels in the tumor. Many chemotherapeutic agents will kill blood vessels as well
as directly killing tumor cells as a way of 'starving' a tumor of oxygen and nutrients. We intend to use this ultrasound
technique to measure blood vessels before chemotherapy and then at set intervals after the onset of chemotherapy in an
attempt to determine if blood vessels in the tumor are dying. We anticipate that this will allow us to predict which dogs are
responding to chemotherapy and ultimately to allow us to determine if a dog should continue with a particular
chemotherapeutic or if they should be switched to another drug that might work better for that individual.

Requirements and incentives: This study is partially funded; the cost of the ultrasounds is paid for. The owner is responsible
for all other fees

GEORGIA
Study: Phase II Clinical Trial Investigating the Efficacy of Vinorelbine and Piroxicam in the Treatment of
Canine Urinary Transitional Cell Carcinoma (TCC)
Location: University of Georgia, Athens, GA
www.vet.uga.edu/research/clinical/Current%20Clinical%20Trials/webpage%20Canine%20oncology%20updated%20Dec.%
202011.pdf

Eligibility: The dogs must meet the following criteria:
1. Dogs with histologically or cytologically confirmed, measurable TCC of the urinary bladder are eligible.
2. Prior treatment is acceptable, but a measurable bladder mass must be present at time of study entry. Dogs must be off all
chemotherapy for a minimum of 2 weeks prior to the start of this trial. Naïve dogs are also considered eligible.
3. Dogs must be free of other severe underlying disease and have adequate bone marrow and organ function.
4. Owners must sign consent form.

Summary: The objectives of this study are to evaluate the efficacy and safety of vinorelbine chemotherapy in combination
with piroxicam in dogs with urinary TCC.

Requirements and Incentives: Owners are responsible for the costs of the initial evaluation and staging procedures. Once
included in the trial, a $1400 UGA hospital credit will be applied to the client’s bill to offset the cost of treatment. The cost of
treatment complications will be NOT be covered by the study.

INDIANA
Location: Purdue University Veterinary School of Medicine, West Lafayette, IN
Phone: For more information, please call (765) 494-1130 and speak with Dr. Knapp, Lindsey Fourez, or Patty Bonney.
www.vet.purdue.edu/pcop/clinical.html

Study: Clinical trial of new chemotherapy protocol
Summary: A new chemotherapy protocol is tested in dogs with transitional cell carcinoma of the urinary bladder. The study
will compare the chemotherapy by itself versus that chemotherapy combined with an NSAID. A diagnosis via tissue biopsy is
required. The chemotherapy will be provided at no cost to the owner, although the owner will be responsible for some costs.

Study: Clinical trial of “metronomic” therapy
Summary: This trial is testing a new therapy approach involving low dose, oral chemotherapy.

Study: Imaging bladder cancer
Summary: A new ultrasound imaging system is being evaluated to more accurately detect and measure bladder tumors.

Study: Folate-targeted therapy
Summary: Because certain cancers in dogs and humans take up the vitamin, folate, Purdue researchers are investigating a
folate/chemotherapy conjugate as a way of selectively delivering therapy to the tumor. Partial funding available.

MISSOURI
Study: Tavocept use to mitigate nephrotoxicity associated with cisplatin and piroxicam treatment of
canine bladder cancer
Location: University of Missouri, Columbia, MO
Phone: 573-882-7821
www.cvm.missouri.edu/oncology/current.html

Eligibility:

Measureable confirmed TCC of the urinary bladder
No previous chemotherapy, radiation therapy or excisional surgery for TCC
NSAID’s must be discontinued for at least 14 days prior to study enrollment
Adequate renal function-normal creatinine and BUN on VMTH panel and adequate urine specific gravity.
No serious or life –threatening concurrent disease reducing life expectancy to < 16 weeks
PCV > 25%, neutrophil count > 2500/ul, platelet count > 100,000
Initial: CBC, UA, serum creatinine and BUN, thoracic rads, abdominal ultrasound/rads, abdominal CT.

Overview: The purpose of this study is to evaluate the efficacy of Tavocept in preventing drug-induced toxicity (especially
nephrotoxicity) associated with cisplatin and piroxicam therapy for canine bladder cancer and to demonstrate that
administration of Tavocept prior to cisplatin chemotherapy in tumor-bearing dogs facilitates the safe use of a shortened
diureses protocol as is the case in people. The overall study goal is to develop a safer (non-nephrotoxic) and more
efficacious treatment regimen for dogs with TCC of the urinary bladder by the use of the novel cytoprotective and antitumor
potentiating agent, Tavocept.

Protocol Overview:

Tavocept infusion over 45 mins, 40 mins later patient will begin 20 minute normal saline diuresis, followed by cisplatin
infusion over 20 minutes, then another 20 minutes of normal saline diuresis.
Treatment will be scheduled every three weeks, with a total of four treatments planned.
Piroxicam will be administered beginning on Day 1 and continue throughout the study
CBC and creatinine to be checked 7 days post chemo administration. CBC and renal panel will be checked prior to
each subsequent therapy.
Tumor response will be assessed on day 42 (+/- 2 days) and day 84 (+/- 2 days) with full staging including abdominal
CT and US.

Incentives: Treatment provided at no cost to the owner. This includes initial staging and follow-up CT scans and abdominal
ultrasounds, blood work done at the VMTH, radiographs, chemotherapy, hospitalization and subsequent office visits at
recheck exams.

OHIO
Study: A Pilot Study of Vinblastine/Palladia Therapy for Canine Transitional Cell Carcinoma
Location: Ohio State University Veterinary Medical Center, Columbus, OH
Contact: clinicaltrials@cvm.osu.edu
http://vet.osu.edu/vmc/pilot-study-vinblastinepalladia-therapy-canine-transitional-cell-carcinoma

Eligibility: To qualify for enrollment in this study, dogs must have:

Measurable TCC of the urinary bladder;
Age > 1 year;
A life expectancy of at least 16 weeks;
No evidence of other illness such as kidney, liver or heart disease;
Not been treated previously with chemotherapy. Previous treatment with NSAIDs and surgery are accepted

Background: Canine transitional cell carcinoma (TCC) of the urinary bladder makes up for 2% of all cancers diagnosed in
dogs, and is a common cancer found in certain breeds of dogs – Scottish Terrier, West Highland White terrier, Beagles and
Shelties. The location of the cancer within the bladder makes surgery often not an option, and the chance of chemotherapy
working in this disease is low – only about 30% of dogs respond to treatment and most only experience stable disease for a
period of time. Therefore, new treatments are desperately needed for this disease. Another problem encountered in the
treatment of this disease is the fact that because the urinary bladder is an organ that can stretch and contract, measuring
bladder tumors accurately and assessing whether treatment is working can be difficult. Ultrasound is currently the method
most commonly used to measure TCC although it is very difficult to do so accurately using this technique and
measurements are often subjective rather than objective. In human cancer therapy, a CT scan is used to measure human
bladder tumors and is the standard practice for determining a response to therapy. Therefore, it is likely that CT scan
would be more accurate to measure bladder tumors in dogs. The purpose of this clinical trial is to first determine whether a
new combination of drugs to treat TCC is more effective than the currently available therapies, and to also determine
whether CT will be more accurate in measuring the TCC before and after treatment.

The two drugs to be combined in this clinical trial are vinblastine, a chemotherapy agent used to treat several different
cancers in dogs, and Palladia, an oral drug that works by blocking the signaling of several receptors, including VEGFR2 and
PDGFR. Both VEGFR2 and PDGFR are important in permitting the growth of new blood vessels, so Palladia works to slow
down or block the growth a blood supply into tumors and prevent them from continuing to grow. There is preliminary
evidence that both vinblastine and Palladia may each have some activity against TCC in dogs. A recent pilot study
demonstrated that 36% of dogs with TCC given vinblastine had their tumor shrink partially following treatment and another
50% had their tumors stop growing for a period of time. In previous work with Palladia, 3 of 4 dogs treated with drug had
their tumors stop growing for a period of time. Vinblastine and Palladia have recently been combined together in a clinical
trial to determine how best to use these drugs together in the setting of mast cell cancer. This study identified the dose of
vinblastine and Palladia that could be safely combined over multiple treatments. These doses will be used in the current
study.

Study design: A total of 10 dogs will be enrolled on this study. Dogs with a diagnosis of TCC of the urinary bladder will have
initial tests performed to determine whether he/she is eligible for the study including bloodwork and chest x-rays. If so, then
a baseline ultrasound scan, CT scan and cystoscopy will be performed. Once these have been completed, patients will
receive vinblastine once every 2 weeks for a total of 8 treatments, and Palladia orally every Monday, Wednesday and
Friday for a total of 16 weeks. All dogs will need to return to the Veterinary Medical Center 1 week following the first
treatment, then every 2 weeks for a total of 16 weeks for physical examination, bloodwork and to receive the vinblastine
treatments. The abdominal ultrasound will be repeated at weeks 4, 8, 12, and 16 of the study (this does not require
anesthesia) and the CT scan will be repeated at weeks 8 and 16 of the study (this does require general anesthesia).

Incentives: The study will cover the majority of the cost associated with the visits ( around $4500 per patient for the total
duration of the study). Palladia will be provided free of charge for 6 months after the study is completed. Owner is
responsible for the initial office visit and screening tests, which is estimated to cost $450 For each treatment visit the
owners are responsible for $57 (hospital and recheck fees).