Copper Chelation as a Novel Treatment for Bladder Cancer in Dogs


Your dog has been diagnosed with a form of bladder cancer termed transitional cell carcinoma (TCC). Unfortunately, treatment of this disease is challenging, as surgical resection is not curative, and current medical treatment is associated with survival times of less than six–nine months in most dogs. Considering these limitations, there is a critical need for new treatment options. Increasing evidence in human and veterinary medicine suggests that depleting copper stores in the body may be of benefit for treating various cancers. Copper is needed for tumor growth and spread, and drugs that bind copper in the body (copper chelators) could have the ability to slow tumor progression. In addition, a specific genetic mutation (activating BRAF mutation) resulting in aggressive cancer behavior is present in most dogs with TCC, and this pathway is dependent upon copper. Considering this information, copper chelation could target multiple pathways in dogs with TCC. However, copper chelators have yet to be investigated in actual dogs with TCC. We hope to determine if copper chelators can improve outcomes for this devastating cancer.

Study Purpose

The purpose of this clinical trial is to investigate the efficacy and adverse effects of ammonium tetrathiomolybdate (TTM), a potent copper chelator, in dogs with TCC. Treatment with this drug as well as monitoring costs, are covered by the study.

Dr. Daniel Langlois of the Internal Medicine Service and Dr. Sonia Honkisz of the Oncology Service are conducting a clinical research study to investigate TTM treatment of TCC in dogs. Please note, enrollment in this study is voluntary and is not necessary for your dog to receive therapy for TCC at the MSU College of Veterinary Medicine and Veterinary Medical Center. Your dog will still receive standard of care therapy if you wish to pursue treatment without study enrollment.

Inclusion and Exclusion Criteria

Inclusion criteria

  • CBC, serum chemistry profile, urinalysis, and urine culture prior to enrollment
  • Abdominal ultrasound in which a bladder mass is identified (performed at MSU)
  • Positive Cadet® BRAF urine test
  • Cystoscopy and tissue biopsy confirms a diagnosis of TCC (performed at MSU)

Exclusion criteria

  • Evidence of TCC causing ureteral or urethral obstruction
  • Evidence of kidney disease, liver dysfunction, or metabolic disease
  • Treatment with anti-inflammatories within four weeks of enrollment
  • Vomiting > 5 times per week (could interfere with drug administration)
  • Consumption of < 50% daily resting energy requirements
  • Inability to comply with the monitoring requirements described below

Dr. Langlois, or your attending veterinarian, can assist with the explanation of any of these criteria to you or your primary care veterinarian.

Study Outline

Participation in the study will require three visits (including the baseline visit) to the MSU Veterinary Medical Center over an approximate two-month time period. Each visit will be separated by one month. Physical examination, bloodwork, and abdominal ultrasound will be performed at each evaluation. A repeat cystoscopy and tissue biopsy (under general anesthesia) will be performed at the final visit. Upon study completion, the care of your dog will be under the discretion of your primary care veterinarian (or your veterinarian at MSU) and will be independent of any study requirements.

Experimental treatment

Your dog will receive treatment with TTM (copper chelator). You will administer the drug orally three times daily for two months. Two of the doses are to be given with meals (morning and evening), and one dose will be given on an empty stomach. You will also be required to maintain a daily medication log to document compliance, record vomiting episodes, and assess for decreases in appetite.

How does this differ from standard care?

  • We do not know if TTM will be an effective treatment for TCC
  • During the trial, your dog will not receive treatment with any standard of care treatments for TCC, which have been associated with survival times of six–nine months
  • We typically do not require owners to maintain medication logs

Investigator responsibilities during the study

The study investigators will closely monitor all patients during this study. Your dog will be immediately withdrawn from the study if tumor volume increases by > 50%, or if the cancer results in evidence of urethral or ureteral obstruction. In addition, possible adverse effects of TTM treatment will be evaluated with bloodwork. We will inform owners of all diagnostic findings in a timely manner.

Dog owner (your) responsibilities

  • To administer TTM as prescribed by the attending veterinarian
  • To comply with the visit schedule outlined by study investigators
  • To report any abnormal behavior or signs of illness to study investigators
  • To contact study investigators if your dog is evaluated by any other veterinarians during the course of the study
  • To inform study investigators of any non-study related veterinary treatments recommended for your dog during the course of the study

Potential complications

  • Your dog will be receiving TTM. This drug has the potential to cause vomiting. Although unlikely, it could also decrease red blood cell counts. Your dog will be closely monitored throughout the study, and TTM doses will be reduced if needed. If severe adverse effects are observed, the drug will be discontinued.
  • Your dog could develop slight bruising at the site of venipuncture for blood collections. This is self-limiting and should resolve in several days without treatment.
  • TCC is an aggressive cancer. Independent of study participation, this will likely be a terminal illness for your dog. If your dog has rapidly progressive disease during the course of the study (as defined above), your dog will be removed from the study. Your dog can immediately receive alternative chemotherapy at this time, but these treatment costs would not be not covered by the study.
  • Similar to above, your dog will go two months without receiving standard of care treatments. If TTM is not effective, this could delay the utilization of standard of care drugs. However, you can withdraw your dog from the study at any time point without penalty if you are concerned with your dog’s progress.

Financial: compensation

  • The study will cover all study scheduled examination fees
  • The study will cover the costs of all study related laboratory evaluations after enrollment as well as the pre-enrollment Cadet® BRAF urine test
  • The study will cover the costs of TTM treatment
  • The study will cover the costs of the baseline and repeat cystoscopy procedure
  • The study will cover the costs of all ultrasonography exams
  • The study will pay for anti-nausea medications for dogs experiencing gastrointestinal upset related to TTM treatment

Financial: owner costs

  • Owners are responsible for pre-enrollment laboratory fees and the initial abdominal ultrasound
  • If adverse effects do occur that are directly the result of study participation, a $250 stipend is allowed for treatment that is performed at the MSU Veterinary Medical Center. Any costs in excess of this are the owner’s responsibility
  • Owners are responsible for veterinary costs in their entirety (both study-related and non-study related) if they are performed at clinics other than the MSU Veterinary Medical Center
  • Owners are responsible for the costs of any chemotherapy drugs after study completion

Study benefits

Participation in this study will help investigators determine if TTM therapy is effective for treating TCC. This information could help revolutionize therapy for this devastating disease. If TTM is effective, it is also possible your dog will experience prolonged survival.

As this is a research study, your dog’s medical information may be shared with additional parties, including publication in a scientific journal. It also is possible that your dog’s medical records could be reviewed by an oversight agency such as the Food and Drug Administration. All identifying information would be removed prior to publication. Enrollment in this study is completely voluntary. If you choose not to participate, standard of care diagnostics and treatment will not be compromised. All study samples and study related data will remain the property of MSU. All study-related questions and concerns may be addressed to Dr. Daniel Langlois at (517) 353-5420.

Please note: You may withdraw your dog from the study at any time point without penalty. This will not affect the quality or type of care that your dog receives. No financial compensation will be given after study withdrawal.

If you’re interested in participating in the study, please contact Dr. Daniel Langlois at (517) 353-5420.