Bladder cancer clinical trials for dogs.

CALIFORNIA
Study: Prospective Evaluation of Urodynamic Testing in Dogs Undergoing Urethral Stent Placement to
Relieve Malignant Urethral Obstruction
Location: University of California Veterinary Hospital Davis, CA
Contact: Dr. Culp at wculp@ucdavis.edu or (530) 752-1393.
www.vetmed.ucdavis.edu/vmth/small_animal/oncology/studies.cfm

Eligibility: Dogs with tumors causing obstruction of the urethra (bladder, urethra and prostate)

Purpose: The purpose of this project is to determine the urethral and bladder pressures of dogs with cancer-induced
urethral obstructions and in dogs with urethral stents.

Summary: Urodynamic studies will be performed at the time of stent placement. Following the urodynamic studies, a urethral
stent will be placed. At 3 weeks post-stent placement, canine continence scores will be obtained from clients regarding the
dog’s voiding habits and urodynamic studies will be performed again.

Benefits: The goal of placing the stent is to improve the dog’s quality of life. All anesthetic episodes (2) will be paid for by the
study. Additionally, all charges associated with the bladder and urethral pressure assessment will be paid for by the study.
There are 2 major study benefits:
(1) We will be able to inform clients of the pressures in their dog’s bladder and urethra and discuss the possible implications
of this; and,
(2) Financial compensation.

Owner Responsibilities: The owner will be responsible for scheduling appointments (initial and 3 weeks after stent
placement) and keeping those appointments as required by protocol. Additionally, the owner will need to fill out forms
related to their dog’s continence status.

Study: Bladder/Urethra Tumors: Assessment and Comparison of Lower Urinary Tract Neoplasia Size
and Location with Multiple Imaging Modalities
Location: University of California Veterinary Hospital Davis, CA
Contact: Dr. Culp at wculp@ucdavis.edu or (530) 752-1393.
www.vetmed.ucdavis.edu/vmth/small_animal/oncology/studies.cfm

Eligibility: Dogs with bladder or urethral tumors.

Purpose: The purpose of this study is to prospectively evaluate dogs with bladder and urethral tumors and assess the best
means for determining tumor size. The overarching goal is to improve our ability to treat these tumors with urethral stenting.

Procedures: Dogs that are undergoing urethral stenting will undergo trans-rectal ultrasound (in addition to abdominal
ultrasound) and MRI evaluation of the bladder/urethral tumor in order to determine tumor size and location.

Benefits: The MRI scan, the trans-rectal ultrasound and the anesthesia associated with these diagnostics will be paid for by
the study. The MRI scan and trans-rectal ultrasound will offer additional imaging modalities that your clinician can use to
make therapeutic recommendations.

Owner Responsibilities: The owner will be responsible for providing follow-up information to the treating clinicians.

INDIANA
Study: Vemurafenib Treatment in Dogs with Bladder Cancer (Transitional Cell Carcinoma).
Location: Purdue University Veterinary School of Medicine, West Lafayette, IN
Email: VeterinaryClinicalTrials@purdue.edu
Phone: (765) 496-9715
Fax: (765) 496-1108

Description: The purpose of this study is to determine the anti-tumor effects, the toxicity (or lack thereof), and the
appropriate dose of Vemurafenib in dogs with TCC. Vemurafenib is a drug that kills tumor cells that have a very precise
mutation. The goal is to improve the outlook for pet dogs and people with cancer.

Eligibility:

Biopsy proof of TCC
Confirmed BRAF V600E mutation in TCC cells in the urine (a urine test)
Measurable cancer lesions that can be followed to assess antitumor effects
Acceptable “performance status” (the dogs still feels OK)
Expected survival ≥ 6 weeks
Acceptable kidney function (serum creatinine ≤ 2mg/dl)

Financial incentive: The pet owner is required to pay $250.00 per month for the expenses incurred in the Purdue University
Veterinary Teaching Hospital (PUVTH) related to the treatment and monitoring. The funding agency will cover the remainder
of the cost related to the Vemurafenib treatment and monitoring in the PUVTH. Any work done outside of the PUVTH or any
expenses not related to the Vemurafenib treatment must be paid by the pet owner.

OHIO
Study: P LX 4720 for Canine Transitional Cell Carcinoma with BRAF mutation.
Location: Ohio State University Veterinary Medical Center, Columbus, OH
Contact: clinicaltrials@cvm.osu.edu

Description: The investigational drug (PLX4720) is a novel small molecule inhibitor of the BRAF, which is a gene involved in
sending signals in cell growth, this gene is altered in many types of cancer. PLX 4720 is closely related to vemurafenib
(Zelboraf, PLX4032), another BRAF inhibitor approved for the treatment of human melanoma carrying activating mutations
in BRAF. It was recently determined that approximately 80% of canine bladder cancer (transitional cell carcinomas-TCC)
carry activating mutations in BRAF identical to those found in human melanoma.

Unfortunately, vemurafenib has unfavorable oral bioavailability in dogs, necessitating the use of another analog with better
pharmacokinetic properties. Recently, healthy volunteer client owned dogs were enrolled into a clinical trial to evaluate the
pharmacokinetics of a single dose of PLX4720 given orally. This was well tolerated and provided critical data regarding
expected pharmacokinetic variability and likely dosing necessary to reach biologically relevant blood levels of drug for the
current clinical trial.

Objective of the trial: To evaluate the biologic activity associated with oral administration of PLX4720 to dogs bladder cancer
and with BRAF mutation, and to assess adverse events associated with chronic PLX4720 dosing.

Eligibility:

Be greater than 1 year of age
Weigh at least 5 kg
Have a diagnosis of transitional cell carcinoma of the bladder with measurable disease
Be medically healthy with no clinically significant physical findings
Prior chemotherapy or radiation must be completed 2 weeks prior to study entry
Be able to receive oral medication on a daily basis
Urine must be positive for the BRAF mutation

Study Procedures: All dogs will receive PLX4270 once per day, dogs will receive PLX4270 for 28 days at which time an
assessment of response to therapy will be performed. If biologic activity is evident, owners will be given the opportunity to
continue on therapy in a compassionate use setting. Recheck exams will be performed at Days 7, 14 and 28 (the final visit).
Analysis of dogs for tumor response will be performed by ultrasound examination of the bladder. Standard clinical
chemistries (CBC, chemistry panel, and urinalysis) will be performed during the study. Additionally, plasma will be collected
at each visit to assess trough blood levels of PLX4270. The initial dose of PLX4270 for dogs will be 30 mg/kg, with dose
escalations in 30 mg/kg increments until a maximum tolerated dose (MTD) is identified or until biologic activity in 50% or
more dogs is documented or until pharmacokinetic analysis determines that no benefit would be obtained by continuing to
increase the dose.

Financial incentive: If your dog participates in this clinical trial, he/she will have the following benefits: complete blood work,
urinalysis, and abdominal ultrasound at the initial visit and at conclusion of the study at no charge to you. In addition the
cost of the recheck exams for Day 0, 7, 14 and 28 will be covered. Owners are financially responsible for the initial exam
fee, BRAF urine testing, thoracic radiographs, and sedation for the abdominal ultrasounds..