Clinical Studies in Oncology - UW Veterinary Care

1) STUDIES FOR SPECIFIC CANCER TYPES

Dogs with Lung Masses

Dogs with a lung mass from cancer or fungal infection may qualify for this study. The study. Breathing creates distortion in a traditional CT scan thus making it more difficult to identify lung tumors. This study compares a traditional diagnostic CT scan to slow CT scan and fluoroscopy to determine the best planning method for radiation therapy. Owners of dogs entered into this study will receive a $150 credit to cover additional anesthesia costs. Please contact the UW Veterinary Care Radiation Oncology Service for more information: radonc@vetmed.wisc.edu or 608-263-7600.

Multicentric Lymphoma in Dogs: Half-Body Radiotherapy In Combination With Chemotherapy For Canine Multicentric Lymphoma: A Recruitment Feasibility Study

Chemotherapy is the treatment of choice for multicentric lymphoma in dogs. Despite high remission rates, relapse is common and cures are rare. Since radiation is a highly effective treatment for some forms of lymphoma in people, we are interested to investigate the potential of radiation used in combination with chemotherapy to extend the remissions of dogs with lymphoma.

Half body radiation (HBRT) has been used for many years to treat the entire canine body (in two halves) with radiation. In order to answer the long-standing question about the benefit of radiotherapy in combination with chemotherapy, a clinical trial is needed. To evaluate the feasibility of performing a larger clinical trial at UW Veterinary Care, this is a recruitment and feasibility study.

Ten dogs with multicentric lymphoma will be recruited to receive HBRT in conjunction with standard chemotherapy. Dogs with previously untreated, stage III to V, non-small cell lymphoma receiving the standard (16-treatment) UW-Madison CHOP chemotherapy protocol will qualify for treatment with radiation. Radiation will be delivered at UW Veterinary Care using the in-house tomotherapy unit mid-way through the chemotherapy protocol. Patients will receive radiation to the front half of the body once a day for two days (4 Gy per day for a total of 8 Gy) after chemotherapy treatment no. 8. The back half of the body will be irradiated in the same manner 4 weeks later. Dogs will be under anesthesia for each radiation treatment. Chemotherapy must be initiated at UW Veterinary Care or at a cooperating oncology specialty practice. Subsequent chemotherapy treatments and follow up visits can be performed at any veterinary facility. Pet-owners will receive special financial considerations to cover the cost of HBRT and essential blood work on the day of radiation treatments. Complete remission is not required, but dogs with progressive disease before irradiation will not qualify.

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.

T-Cell Lymphoma in Dogs: Defining Anticancer Activity of Systemic Oncolytic Virus (VSV)

Dogs with T-cell lymphoma might be eligible for a clinical trial to define the optimal dose and schedule for an oncolytic virus treatment (VSV-IFNβ-NIS). Note: This study is temporarily on hold until late August, 2018.

This clinical trial led by the National Cancer Institute assesses the safety and effectiveness of a cancer-killing virus (VSV-IFNβ-NIS) when given to dogs with cancer. This virus is currently being evaluated in human patients with liver cancer in an FDA-approved trial. However, additional information in other types of cancer is needed to support new clinical trials.

This clinical trial involves administration of a fixed dose of VSV-IFNβ-NIS in dogs with cancer. Studies in mice, normal dogs, and in a small study of pet dogs with cancer have shown the virus to be safe at certain doses (including the dose to be used in this study). Side effects that have been observed in normal dogs include fever, vomiting and poor appetite, which resolve within 24-48 hours. Less commonly, mouth blisters and bacterial urinary tract infections have been observed; both of which resolved with time and specific antibiotic treatment, respectively.

VSV-IFNβ-NIS is a live virus and in order to prevent spread to other animals via fleas, ticks or biting flies, dogs in this study must be treated with external and internal parasite control medications, and be up-to-date on standard vaccinations.

Within this study, dogs will receive one or two doses of VSV-IFNβ-NIS depending on which arm of the study the dog is placed. Close observation and confinement during the period of viremia (active virus in the bloodstream) will require overnight boarding at UW Veterinary Care for 4 days. Collection of a tumor biopsy will be required before treatment. Collection of blood and urine will be required prior to and after treatment.

After discharge from the hospital, the patient is required to return to UW Veterinary Care for follow-up visits weekly (Day 8, 15, 22 and 29).

Once a dog is enrolled, the study will cover all costs associated with study-related treatment and follow-up. In addition, there is a $2,500 credit at UW Veterinary Care as an incentive for participating. In the event any complications arise during the study period, their management will be covered by the study funds up to $2,000/per dog/per event. This would include any unanticipated hospitalizations after the first 4 days of in-patient treatment.

Nasal Tumors (Sarcoma or Carcinoma): Stereotactic Radiation Therapy for Dogs with Nasal Tumors

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Nasal tumors are locally aggressive tumors of the nasal passages. Radiation therapy is the treatment of choice for dogs affected by this cancer. At UW Veterinary Care, we have a TomoTherapy radiation delivery system which targets radiation to the tumor while sparing the surrounding normal tissues from side effects. Stereotactic radiotherapy (SRT) is the use of this very precise technology to deliver high doses of radiation in fewer treatments compared to conventional protocols. A conventional radiation protocol for nasal tumors involves 10 radiation treatments, given as one treatment per day for 10 days. To take advantage of the extreme accuracy of stereotactic radiation therapy, we are investigating the efficacy of a shorter protocol in which only 3 treatments are delivered over one week (on Monday, Wednesday and Friday). Compared to the conventional protocol, a higher dose of radiation is used for each treatment to achieve a similarly effective total dose. Potential benefits of stereotactic radiation therapy include fewer visits to the hospital for radiation treatments, fewer anesthetic events, and a lower risk of short-term side effects. We will assess the safety of this new approach by monitoring for any radiation-induced changes in the eye. Our hypothesis is that by delivering stereotactic radiation therapy, we will safely decrease the number of treatments needed to effectively treat nasal tumors in dogs. Dogs with a biopsy-confirmed diagnosis of cancer affecting the nasal cavity (carcinoma or sarcoma), stages I-III may be eligible to participate in this study. Dogs with cribriform plate involvement and/or metastasis, or previous treatment for this cancer are not eligible. Dogs will be evaluated at 2 & 4 weeks and 3 & 6 months post-radiotherapy to assess tumor response and side effects, including ocular changes. Clients will receive financial compensation to cover the cost of their dog’s follow-up evaluations, including scheduled hospital visits for a full examination including eye exams and a post-treatment CT scan.

Osteosarcoma: Evaluation of a Recombinant, Attenuated Listeria Monocytogenes Expressing a Chimeric Human Her2/neu Protein (ADXS31-164^c ) in Dogs With Osteosarcoma in the Adjuvant Setting

Bone cancer or osteosarcoma (OSA) 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. The immune system plays an important role in identifying and targeting cancer cells in the body. In this study, we aim to use a new approach to stimulate the body’s own immune system to attack remaining tumor cells in dogs that have undergone limb amputation and chemotherapy for the treatment of OSA. We will use a vaccine made from the bacteria Listeria monocytogenes, which has been genetically modified to express a tumor protein (HER-2/neu) that is found in many cancer cells, including canine bone cancer cells and cancer stem cells. When injected into the bloodstream, the modified Listeria stimulates the immune system to attack cells expressing the HER-2/neu tumor protein. This approach aims to delay and/or prevent the spread of cancer (metastases) following removal of the primary bone cancer tumor (limb amputation) and chemotherapy.

To qualify for this study, we ask that you permit surgical amputation of your dog’s affected limb. Your dog will return to UW Veterinary Care every 3 weeks for 15 weeks for evaluation. On weeks 3, 6, 9 and 12 your dog will receive a dose of carboplatin (standard of care for OSA). Blood work will be done on your dog prior to carboplatin administration. After 15 weeks, your dog will be administered 3 doses of ADXS31-164^c. Doses will be administered every 3 weeks for a total of 3 treatments.

Clients of dogs entered into this study will receive financial compensation, which will cover the cost of the initial physical examination and ultrasound, all physical examinations and radiographs, and the costs associated with ADXS31-164^c treatment and follow-up evaluations. Clients are responsible for the cost of diagnosis, amputation, and for the carboplatin chemotherapy.

Lymphoma in Boxer Dogs

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We are interested in whether certain gene defects, in addition to exposure to certain environmental chemicals, contribute to the risk of lymphoma in boxer dogs.

We are looking to obtain cheek swab samples from boxers diagnosed with lymphoma. In addition, we have an environmental exposure questionnaire for the owners to complete. We are also recruiting healthy boxers of any age and any dog over 10 years of age for a control dog comparison.

Eligibility: Any boxer diagnosed with lymphoma qualifies for the study. Dogs can be enrolled at any time after diagnosis and may be on any treatment protocol. The inside of the patient’s cheek will be swabbed with a special brush for DNA collection (kit with brushes, instructions, owner questionnaire and free mailing provided). The swabs and environmental questionnaire will be processed by Dr. Lauren Trepanier‘s laboratory. For more information or for a DNA sampling kit, please contact Joanne Ekena

2) STUDIES FOR ANY CANCER TYPE

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.

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. For more information, contact Dr Robb Hardie at robert.hardie@wisc.edu.

5) STUDIES FOR AGE RELATED DEBILITATION

Dogs with Age-Related Debilitation

Age Related Debilitation Study Flyer

The Primary Care Service, in cooperation with the Oncology Service, is recruiting dogs for an age-related debilitation study.

Most dogs, regardless of breed, experience some form of age-related debilitation as they get older. Symptoms of age-related debilitation include confusion, anxiety or restlessness, decreased desire to play, and changes in sleep cycle. We are investigating a novel drug (RPh201) that has been found in preliminary studies to restore some of the cognitive and biological effects of aging. RPh201 is a botanical extract isolated from the mastic tree, which grows primarily in dry and rocky areas in Mediterranean Europe.

The objective of this study is to evaluate the safety and preliminary efficacy of RPh201 for Injection in dogs with age-related debilitation when administered once weekly for 16 weeks. This is a placebo-controlled study in which dogs are randomized to receive either RPh201 or placebo. Given the design of the study, a dog is twice more likely to receive RPh201 than to be given a placebo. At the study end visit (week 17), the treatment code will be broken and if a dog has been receiving placebo, the dog will be eligible to receive 16 weeks of treatment with RPh201 at no cost.

Dogs at least eight years old and deemed cognitively or otherwise age-debilitated may be eligible for this study. Upons completion of the study, clients receive a UW Veterinary Care credit. For more information, please contact the UW Veterinary Care Oncology Service at 608-263-7600 or Dr. Kara Magee at kmagee3@wisc.edu.