Clinical Studies in Oncology

1) STUDIES FOR SPECIFIC CANCER TYPES

Bladder Cancer in Dogs: Genetic and Environmental Risk Factors

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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 bladder cancer in dogs.

We are looking to obtain cheek swab samples from dogs of any breed diagnosed with bladder cancer. In addition, we have an environmental exposure questionnaire for dog owners to fill out.

Eligibility: Any dog diagnosed with transitional cell carcinoma of the bladder or urethra. Dogs can be enrolled at any time after diagnosis and may be on any treatment protocol. The inside of the dog’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. Please contact Katherine Luethcke, DVM/PhD student at 608-263-5520 or luethcke@wisc.edu with any questions or to obtain a DNA sampling kit.

Dogs with Lung Masses

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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

Scroll down to Dogs with Any Cancer: Defining Anticancer Activity of Systemic Oncolytic Virus (VSV). This study is looking to enroll primarily dogs with T-cell lymphoma.

Dogs with Melanoma or Mast Cell Tumors

This trial is designed to evaluate the safety and preliminary anti-cancer activity of a novel monoclonal antibody in dogs with measurable melanoma or mast cell tumor. An estimated 20 client-owned dogs will be enrolled. The antibody is administered intravenously by the study staff every 14 days for up to 10 treatments. No placebo is used in this trial. Clinic visits will be required when the dog begins the study and then every 2 weeks for a period of 140 days.

Trial Funding: The trial is fully funded for the full duration (140 days), including the antibody and trial-related procedures.

Criteria for Entry: Dogs with mast cell tumors must have at least one measurable skin tumor (+/- metastatic lymph node(s)) greater or equal to 2 cm and no intraabdominal metastasis (abdominal ultrasound will be performed at screening). Dogs with melanoma must have at least one measurable tumor in the oral cavity, digit, or skin (+/- metastatic lymph node) greater or equal to 2 cm and no pulmonary metastasis (lung x-rays will be performed at screening). Prior therapy for mast cell tumors or melanoma is acceptable with washout times to be discussed with the clinician.

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.

Canine Osteosarcoma

We currently have 2 studies for dogs with osteosarcoma:

• Evaluation of the Effect of Rapamycin Following Amputation and Carboplatin Chemotherapy on Disease-Free Survival in Dogs with Appendicular Osteosarcoma

This clinical trial led by the National Cancer Institute (NCI) and sponsored by the Morris Animal Foundation seeks to evaluate in dogs with osteosarcoma the safety and effectiveness of Standard of Care therapy, with or without adjuvant rapamycin administration. Standard of Care is defined as definitive surgery, being amputation of the affected limb, followed by 4 doses of intravenous carboplatin chemotherapy given on a q21 day schedule. Carboplatin has been safely and effectively used to treat appendicular osteosarcoma in dogs for > 20 years, but the potential for unforeseen potentially life-threatening side effects from surgery, chemotherapy, and/or progressive cancer does exist. ALL dogs enrolled onto study will receive Standard of Care therapy; however, through a randomization process, some dogs entered into study will also receive additional therapy with oral rapamycin.

Rapamycin is a drug currently approved for immunosuppression during preparatory and maintenance regimens for organ and bone marrow transplant in human patients. Early work with rapamycin suggests that this agent might also have anti-cancer properties by inhibiting (reducing the effects of) an important pathway in cancer progression known as mTOR. Preclinical studies of rapamycin in mice, as well as recent data using analogous drugs in human patients (rapalogs), suggest that mTOR blockade might be effective in the treatment of several cancers. In a recently completed study of rapamycin in dogs with cancer, a dose and schedule for rapamycin administration have been defined which appears to be safe and tolerable by most dogs.

Within this study, dogs will undergo surgical amputation of the affected limb. Dogs will return to UW Veterinary Care every 3 weeks for 15 weeks for evaluation. On weeks 3, 6, 9 and 12, dogs will receive a dose of carboplatin. After 15 weeks of Standard of Care, based upon initial study randomization, dogs will either receive oral rapamycin on a 4 day on/3 day off schedule for 4 months or will not be treated with any additional medications and simply be monitored every 8 weeks.

Costs associated with this study (including carboplatin and rapamycin administration and study-related evaluations will be covered by the study. In addition, $1,000 will be provided towards the cost of surgical amputation.

• Stereotactic Radiation Therapy for Pain Relief and Immune Modification in Dogs with Limb Osteosarcoma

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Radiation therapy’s primary use for canine osteosarcoma has been with a palliative intent to alleviate pain. Stereotactic radiation therapy (SRT) is a highly accurate radiation delivery technique that potentially allows us to give a higher radiation dose per treatment in fewer treatment sessions. This study will deliver 3 radiation treatments over 3 days and assess pain relief with orthopedic exam, force platform analysis and client questionnaires. The primary aim of this study is to determine the effectiveness of stereotactic radiation therapy to alleviate pain. We hypothesize that most dogs will experience significant pain relief.

Large doses of radiation per treatment have also been proposed to stimulate an immune response against the cancer. To evaluate this, we aim to measure changes in proteins released from the tumor or its environment by collecting blood samples before, during and after the radiation therapy.

Two weeks following completion of the third radiation treatment, dogs will start intravenous carboplatin chemotherapy. Carboplatin will be administered once every 3 weeks for a total of 4 treatments.

Dogs with a biopsy confirmed diagnosis of osteosarcoma of the limb may be eligible for this study. Dogs with a tumor-related fracture, spread of cancer to lymph nodes or lungs or previous radiation or chemotherapy are not eligible. A CT scan will be required for radiation planning and to determine study eligibility. Dogs will be evaluated at 1, 2, 4, 5, 7, 8, 10, 11, 12, and 14 weeks after radiation therapy. Clients will receive financial compensation, which will cover the cost of radiation therapy and follow-up force plate evaluations. Clients are responsible for the cost of diagnosis and tests to determine if their dog is eligible for this study, recheck examination fees, 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.

Dogs with Any Cancer (except hemangiosarcoma and mast cell tumor): Defining Anticancer Activity of Systemic Oncolytic Virus (VSV)

Dogs with any cancer (except hemangiosarcoma and mast cell tumor) might be eligible for a clinical trial to define the optimal dose and schedule for an oncolytic virus treatment (VSV-IFNβ-NIS).

This clinical trial led by the National Cancer Institute and Omnis, Inc. 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 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 blood, urine, feces, and tumor biopsies 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) and on Day 56.

Once a dog is enrolled, the study will cover all costs associated with study-related treatment and follow-up. In addition, there is a $1,000 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.

Risk Factors for Cytoxan (cyclophosphamide) Toxicity in Dogs

We are looking to obtain cheek swab samples from dogs treated with cyclophosphamide, who have developed sterile hemorrhagic cystitis. We are interested in whether certain drug detoxification gene defects put dogs at risk for cyclophosphamide toxicity. Eligibility: Any dog treated with cyclophosphamide that develops subsequent sterile hemorrhagic cystitis. Dogs must have had a negative urine culture to rule out bacterial cystitis. The inside of the dog’s cheek will be swiped with a cotton swab. The swabs will be collected in the Oncology ward and processed by Dr. Lauren Trepanier’s laboratory (Joanne Ekena MS, 608-263-5520 ekena@wisc.edu)

3) STUDIES EVALUATING THE IMMUNE SYSTEM OF DOGS WITH OSTEOSARCOMA & THE IMPACT OF THERAPY ON IMMUNE RESPONSE

Dogs: Evaluating the impact of surgery and radiation therapy on circulating immunocytokine levels in dogs with appendicular osteosarcoma.

Osteosarcoma is an aggressive bone cancer of middle aged to older dogs. Approximately 90% of dogs will develop metastatic lesions. Currently, the ability to control local disease with surgery is excellent, unfortunately our attempts to control metastatic disease have mostly failed, with a cure rate of less than 10%. Few advances have been made to improve upon these numbers over the past 20-30 years. The use of treatments to stimulate the immune system have been found to improve survival times in dogs with osteosarcoma, highlighting the importance of the immune system in osteosarcoma.  However, little information exists regarding the immune system of dogs with osteosarcoma compared to dogs without cancer. Additionally, no information exists regarding the impact of treatments on the immune system of dogs with osteosarcoma.  This study aims to provide information in these two areas. Our pilot study will compare the immunocytokine profile in dogs receiving either local radiation therapy or surgery (limb amputation) for treatment of appendicular osteosarcoma. For this study, a small amount of blood will be taken from dogs undergoing radiation therapy or amputation at UW Veterinary Care for treatment of their osteosarcoma.

Inclusion criteria: Dogs undergoing radiation therapy or amputation at UW Veterinary Care for treatment of their osteosarcoma. Dogs with histologically confirmed appendicular osteosarcoma of any clinical stage will be eligible for enrollment. Dogs receiving non-steroidal anti-inflammatory drugs (NSAID) will be eligible for study enrollment.

Exclusion criteria: Dogs having received prior surgery, radiation therapy, or cytotoxic chemotherapy.

Please contact Dr. Dr. Elizabeth Wood if you have any questions about the study or for study enrollment: 608-263-7600.

4) STUDIES EVALUATING CHEMOTHERAPY SIDE EFFECTS

None at this time.

5) 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.