Clinical Studies in Oncology - UW Veterinary Care

1) STUDIES FOR SPECIFIC CANCER TYPES

B-Cell Lymphoma in Dogs: Evaluating the effect of regulatory T cell and killer T cell numbers in blood and tumor tissues of dogs with B cell lymphoma on progression-free survival

Lymphoma accounts for nearly 25% of all canine neoplasms, and 60-80% of these are of B-cell origin. With standard chemotherapy, median survival times for canine B-cell lymphoma (BCL) range from 12 to 18 months. However, critical decisions about patient care currently rely on prognostic indicators that are often unreliable or poorly predict the biological behavior of BCL. Significant improvements in patient care will require identification of new biomarkers that are predictive of clinical behavior. Recent studies in dogs and humans demonstrate a link between anti-tumor immune responses and the biological behavior of tumor.

Regulatory T lymphocytes (Tregs) are immune cells normally tasked with preventing harmful autoimmune responses. However, in some tumors increased frequency of Tregs can impair protective anti-tumor immune responses. The relationship between Treg infiltration and progression-free survival is not clearly defined in dogs with BCL. We hypothesize that Treg frequency and ratio to CD8+ T cells in BCL will be correlated with clinical behavior. We also postulate that Treg frequency and Treg:CD8+ ratios will act as prognostic indicators of survival and may help identify novel targets for anti-cancer therapy.

Eligibility: Criteria for inclusion in this study include newly diagnosed multicentric BCL (World Health Organization [WHO] stage I-IV) and willingness to start standard-of-care CHOP chemotherapy. Owners must be willing to return to UW Veterinary Care one week after initiation of chemotherapy, as well as at the time of relapse. Patients with WHO stage V BCL (leukemic patients), or evidence of concurrent disease other than BCL or who have undergone previous chemotherapy or steroid treatment will not be eligible. Dogs enrolled in the study will undergo a blood draw and lymph node aspiration at enrollment, following 1 week of chemotherapy, and at the time of clinical relapse. Once a dog is accepted as eligible, the study will pay for immunocytochemical analysis of lymph node aspirates to confirm the tumor’s immunophenotype.

Lymphoma: Evaluation of Adding Tanovea to Standard of Care Chemotherapy in Dogs with Newly Diagnosed Lymphoma

Lymphoma is one of the most common cancers in dogs. Current treatment options include various types of chemotherapy including Tanovea-CA1 (rabacfosadine for injection), the first FDA conditionally approved drug to treat canine lymphoma. It is an intravenous chemotherapy agent that has been used in more than 600 dogs with cancer. The goal of this study is to evaluate the effectiveness and safety of the addition of Tanovea to a chemotherapy protocol containing prednisone, vincristine, cyclophosphamide, and doxorubicin in dogs with previously untreated multicentric lymphoma.

Dogs with newly diagnosed lymphoma may be eligible for this study. The study provides Tanovea at no cost. Owners are responsible for all other costs including the intravenous administration of Tanovea.

Melanoma Without Metastasis: Evaluation of a Novel Immunotherapy in Combination with Radiation Therapy in Dogs

NOTE: This study is on hold while we install our new radiation therapy unit. The study will reopen at the end of September.

In a study funded by the Veterans Administration we will evaluate the effect of a novel immunotherapy agent administered into the tumor in combination with radiation therapy.

Dogs with melanoma that have a tumor accessible for intratumor injection may be eligible for this study. There will be 2 treatment groups: one group will receive one dose of radiation and one group will receive 3 doses of radiation, both groups will then receive daily injections for 3 days of the immunotherapy agent into the the tumor. Following treatment, dogs will return to UWVC for evaluation on days 10, 17, 24, 30, and 60.

Once a dog is deemed eligible for the study, all costs related to the study will be covered including the radiation therapy and immunotherapy.

Melanoma With Metastasis: Evaluation of a Targeted Radiation Treatment Combined with an Immunotherapy Treatment for Dogs with Metastatic Melanoma

NOTE: This study is on hold while we install our new radiation therapy unit. The study will reopen at the end of September.

In collaboration with the UW Carbone Cancer Center, we are developing a new approach to the treatment of melanoma that has spread beyond the primary tumor (metastatic cancer) utilizing immune responses to recognize and destroy cancer (immunotherapy) in combination with low-dose radiation therapy, which may improve the anti-tumor potency of the immunotherapy.

Dogs will first receive a radioactive imaging agent prior to the performance of 3 daily PET scans. The findings of the PET scans will determine the dose of the radioactive anti-tumor agent which will be delivered intravenously one week later. Two weeks after the radioactive anti-tumor agent is delivered, the dog will receive one conventional radiation therapy treatment, immediately followed by treatment with the intravenous radioactive anti-tumor agent. One week later, an immunotherapy agent will be administered directly into the dog’s tumor, once daily for 3 days. Because the imaging agent and the intravenous radiation agent are radioactive, dogs must remain in the hospital until it is determined that the appropriate level of radioactivity has been reached to allow the dog to return home: this will be approximately 4 – 6 days following administration of the imaging agent or the intravenous radiation treatment.

All costs associated with initial screening to determine eligibility and costs associated with treatment, scans, hospitalizations, and study follow-up are paid for by the study. In addition, a $500 credit will be applied to your UW Veterinary Care account which can be used following your dog’s completion of this protocol.

Dogs with Nasal Tumors: Evaluate the Effect of Radiotherapy on Oral Health in Dogs

Radiation therapy is the standard of care treatment for nasal cavity cancer in dogs. It is well known that in humans pre-existing dental disease worsens radiation-induced complications in the mouth. Because of these complications, pre-irradiation dental care is crucial for human patients. The relationship between radiotherapy and oral health has not yet been investigated in dogs. This study is being conducted to document oral health after radiotherapy, including periodontal change, severity of inflammation of the lining of the mouth (mucositis), and measures of quality of life in dogs with nasal tumors.

Dogs with sinonasal tumors who are undergoing a curative-intent radiation protocol at UW Veterinary Care may qualify for this study.

Dogs will undergo standard radiation treatment. Radiation exposure will be variable, and each dog’s radiation treatment will be planned using the tomotherapy computerized treatment planning system, so the radiation dose delivered to each tooth will be documented. Periodontal disease will be evaluated at three time points, day 1 of radiation treatment, 3 months after radiation treatment, and 6 months after radiation treatment. Mucositis will be evaluated on day 1 of radiation treatment, the last day of radiation treatment, at weeks 1, 2, 3, and 4 after radiation treatment, and then again at 3 months and 6 months after radiation treatment. At the 3-month and 6-month recheck visits, patients will be placed under general anesthesia for oral examination and radiographs.

Osteosarcoma in Dogs that are Not Candidates for Amputation: Evaluation of the Safety and Effectiveness of a Novel Bone-Targeting Agent in Combination with Chemotherapy

While surgery, radiation therapy, and conventional chemotherapy can be useful for the management of osteosarcoma in dogs, not all dogs may be candidates for treatments like surgery or radiation. A new drug, GEM-IB, combines a bone-targeting drug (ibandronate) with a potent cancer drug (gemcitibine) to increase the concentration of cancer drug exactly at the site of the tumor. This drug has shown good activity against osteosarcoma and laboratory studies suggest that combining this drug with the conventional chemotherapy drug docetaxel significantly improves effectiveness.

In this study, dogs will receive both drugs intravenously once every 21 days. Dogs will need to return to UWVC for evaluation on days 1, 3, 7, 14, and 21 after treatment. The visits on day 0, 7 and 21 will likely take all day, while the other visits will likely require approximately 1 hour. The dog will be eligible to continue receiving treatment at no cost as long as the drug is tolerated and the dog is experiencing clinical benefit (pain control and lack of tumor worsening). Analysis for tumor change will be performed through the use of imaging (X-rays, PET-CT), and limb use will be measured through gait analysis. Standard bloodwork will be performed at each visit. Additional tests to be performed include blood/urine collection over the course of the study to determine how the investigational drug is affecting changes in bone turnover. Imaging will be performed using standard sedation/anesthesia protocols.

Costs covered by the clinical trial for eligible enrolled dogs include: all costs associated with all treatments and treatment of any side effects associated with the treatment. Following the dog’s completion of the clinical trial, the owner will receive a credit of $1,000 (one thousand dollars) for continued treatment at UW Veterinary Care, if the owner chooses to do so.

Osteosarcoma with Lung Metastasis: Evaluation of a Novel Anticancer Drug in Combination with a Common Chemotherapy drug for the Treatment of Osteosarcoma Metastasis

NOTE: This study is currently on hold until further notice.

Bone cancer (osteosarcoma) is a common, highly aggressive cancer that frequently affects the long bones of large breed dogs. Current therapy consists of limb amputation plus chemotherapy. However, despite therapy, most patients die as a result of the cancer spreading to other parts of their body, most commonly to the lungs. The purpose of this clinical trial is to evaluate the safety and efficacy of a novel anticancer drug (PAC-1) combined with a commonly used chemotherapy drug (doxorubicin) for dogs with osteosarcoma that has spread to their lungs. PAC-1 is a new drug that can sensitize osteosarcoma tumor cells to the killing effect of doxorubicin.

For dogs to be eligible for this clinical trial they must have a confirmed diagnosis of osteosarcoma with spread to the lungs and have had a previous amputation, limb spare or stereotactic radiation of the affected limb. Dogs will receive a total of 4 doses of intravenous doxorubicin (at 2-week intervals) and PAC-1 given orally once daily for 7 days prior to each doxorubicin treatment.

Owners are responsible for eligibility requirements (blood work, chest x-ray, abdominal ultrasound). Following enrollment, the study will cover the costs of PAC-1 and doxorubicin, and all study-related evaluations and follow-up.

2) STUDIES FOR ANY CANCER TYPE

Dogs With Any Cancer (Except Lymphoma or Leukemia): Evaluation of the Antitumor Effect of Administration of the Dog’s Own Activated Immune (T) Cells

Recent evidence in rodent models suggest that a very brief incubation of a sample of immune cells present in the blood (T-cells) with a novel immune-stimulating agent results in significant activation of the T-cells and these activated T-cells can have substantial antitumor activity. The objective of this study is to evaluate the safety and efficacy of treatment with activated T-cells (TBX-3440). The treatment procedure involves collecting a blood sample from the dog, isolating T-cells in the laboratory, and exposing the T-cells to the activator. The activated T-cells (TBX-3440) are then administered intravenously to the same dog. Dogs will be monitored closely for tumor response and potential side-effects. The doses to be used in this study have been evaluated in normal dogs and dogs with cancer and no adverse effects have been observed.

The dog will receive TBX-3440 once every 2 weeks. For dogs experiencing a complete response (disappearance of all lesions), treatment will be discontinued after 12 weeks or 8 weeks beyond achievement of the complete response, whichever is longer. Dogs that have stable disease or a partial response will continue to receive TBX-3440 every 2 weeks for as long as there is no evidence of progressive disease. The dog will need to come weekly for the first 4 weeks, then every 2 weeks while receiving treatment on this study. Dogs with a complete response will only need to return monthly after achieving this response. Routine blood samples will be collected at each clinic visit and a urine sample will be collected every 2 weeks up to week 4, then monthly thereafter. X-rays and an abdominal ultrasound may be performed prior to treatment to assess extent of disease.

The owner is responsible for the costs to determine eligibility for this study (physical examination, initial blood work and urinalysis, and if indicated, X-rays and possibly an abdominal ultrasound). Costs covered by the clinical trial for eligible enrolled dogs include: all costs associated with all treatments and study evaluations. Any side effects associated with treatment will be covered up to $500 (five hundred dollars).

Following the dog’s completion of the clinical trial, the owner will receive a credit of $1,000 (one thousand dollars) for additional therapy. A portion of the $1,000 additional therapy fee can be used to offset the initial diagnosis and staging costs.

Dogs With Any Cancer with a Tumor Accessible to Biopsy: Evaluate the Biological Effective Dose and the Tolerability of Trametinib

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This study investigates a novel drug, trametinib, that specifically ‘targets’ a growth signaling pathway found in cancer cells from companion (pet) dogs. This study will determine the optimal dose that is both safe and effective in shutting down the cancer’s growth signals in dogs diagnosed with aggressive cancers. Additionally, the study will test whether a simple blood test can be used to quickly determine whether effective drug levels are present in the dog. Finally, preliminary evidence of meaningful anticancer activity (cancer shrinkage) will be documented in order to determine if this novel drug should be studied in larger populations of dogs with aggressive cancer.

Prior to treatment, a tumor biopsy, blood sample, and urine will be collected. X-rays and if indicated, a CT scan and/or abdominal ultrasound will be performed. Trametinib will be administered orally, once daily, for up to 3 consecutive 21-day cycles. The first and 7^th day that trametinib is administered (for the first cycle only), the dog will need to stay in the hospital for the day for collection of timed blood samples. The dog will need to return for collection of a blood sample on Day 2 and 8. Dogs will return for evaluation on day 21 and then every 21 days thereafter until the dog has evidence of cancer progression. Starting on day 42 and every other 21 days thereafter (until there is evidence of disease progression), X-rays and if indicated, a CT scan and/or abdominal ultrasound will be repeated to monitor the dog’s response to treatment.

Trametinib will be supplied at no cost. The study will pay for the recheck physical examination fees, collection of blood and tumor samples for investigation, and routine laboratory tests at scheduled study recheck visits. The owner will be responsible for all costs associated with initial screening to determine eligibility (physical examination, laboratory tests, X-rays and/or CT scan and/or abdominal ultrasound), and, if indicated, a follow-up CT scan.

Cats With Any Cancer: Safety Evaluation of Low-Dose Meloxicam in Combination with Palladia

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This study will investigate if meloxicam, an anti-inflammatory medication, can be used safely in combination with Palladia™, a targeted chemotherapy agent, in cats with naturally occurring cancer.

Any cat that presents to the UW Veterinary Care Oncology Service who is diagnosed with any tumor type, as long as the cancer does not involve the kidneys, may qualify for this study. Patients will receive standard doses of Palladia™, as well as low doses of meloxicam to help manage pain, reduce inflammation, and for its anti-cancer potential. At each visit, owners will be asked to answer a questionnaire, and the patient will be assessed by a veterinarian to determine the impact of this drug combination on the patient’s quality of life.

Owners are responsible for the costs of initial consultation and staging tests (pre-treatment CBC/chemistry/blood pressure/urinalysis/and any imaging tests if necessary), as well as additional imaging tests as needed for disease monitoring and rechecks associated with side effects. The study will cover the costs of recheck exams on designated days with labwork and blood pressure monitoring as indicated, as well as costs of the meloxicam and Palladia™ medications.

Cats With Any Cancer: Safety Evaluation of Palladia (Toceranib Phosphate) in Combination with Doxorubicin

Previous studies have shown that the drug Palladia (toceranib) can reverse resistance to doxorubicin (a commonly used anticancer drug). We have recently completed a study evaluating toceranib in combination with doxorubicin as treatment for cancer in dogs. The combination was well tolerated and the maximum tolerated dose of doxorubicin when combined with Palladia was determined. The goal of this study is to evaluate the safety and maximum tolerated dose of combination toceranib and doxorubicin in cats with naturally occurring cancer.

Cats that have a confirmed diagnosis of new or recurrent cancer may be eligible for this study. Cats will receive Palladia every other day (given orally by the owner). Doxorubicin will be administered intravenously every 3 weeks for a total of 4 treatments. Cats will be evaluated prior to each doxorubicin treatment and one week after each treatment for assessment of side effects and efficacy of this combined treatment.

The owner is responsible for the cost of initial staging (including pretreatment labwork and pretreatment blood pressure measurement) and recheck examination fees throughout the study period. The study will cover all other study-related costs.

Dogs With Any Cancer (except mast cell tumor or hemangiosarcoma): Evaluation of a Novel Oral Anticancer Agent

This clinical trial led by the National Cancer Institute is evaluating the safety and effectiveness of CB-5339, a novel anticancer agent, when given orally to dogs with cancer. Dogs with any cancer (except mast cell tumors or hemangiosarcoma) may be eligible for this study. CB-5339 is administered for orally, once daily for 4 consecutive days the first week and again for 4 days the second week.

Tumor biopsies will be performed prior to treatment and again on study days 1, 2, 8, and 22. Blood samples will be collected prior to treatment and again on study days 1, 2, 8, 15, and 22. Costs related to the study will be covered by the study. In addition, a $1,000 credit will be applied to your UW Veterinary Care account which can be used towards additional treatment of your dog’s cancer following your dog’s completion of this protocol.

Healthy Dogs of Certain Breeds: Vaccination Against Canine Cancer Study

UW Veterinary Care’s Oncology Service is recruiting dogs for the Vaccination Against Canine Cancer Study (VACCS trial), the largest clinical trial conducted to date for canine cancer. The goal of the VACCS trial is to evaluate a new vaccine strategy for the prevention, rather than treatment of dogs with cancer.

Healthy dogs of certain breeds, 6 to 11.5 years of age, will be randomized to receive either a series of vaccines similar to other routine vaccines that are given to dogs currently, or placebo vaccines. Dogs will live at home and be checked 2-3 times yearly for 5 years after enrollment. A financial incentive will be offered to defray the cost associated with diagnostics and treatment of any cancers that dogs develop, regardless of whether they are receiving vaccine or placebo.

In addition to potentially providing a new strategy for cancer prevention in dogs, if successful, this study could provide important justification for eventually looking at a similar approach in humans.

4) BIOPSY STUDIES

Dogs with Mast Cell Tumors

The General Surgery Service is looking for dogs with mast cell tumors. The goal of this study is to compare the histopathological grade of samples obtained from a punch biopsy to samples obtained from a whole tumor specimen. The surgeons surgically remove the tumor in a routine manner according to the normal standard of care. Punch biopsies are taken of the removed tumor. Three pathologists examine the punch biopsies, along with the complete tumor samples, to determine the grade of mast cell tumor. The results are then compared. The goal is to determine if mast cell tumors can be accurately graded from a smaller, less invasive, sample size.