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.

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.

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

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.

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.

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