UW-Madison School of Veterinary Medicine Clinical Trials

We are currently enrolling patients in clinical trials in the Emergency Services/Critical Care, Oncology, Ophthalmology, Internal Medicine, and Orthopedic Surgery Services.

Emergency Services/Critical Care

DOGS: Incidence of bacterial infections in Febrile and Afebrile neutropenic patients undergoing chemotherapy

Inclusion criteria: For this prospective observational study, we are enrolling current canine chemotherapy patients with<1500 neutrophils/uL.

The purpose is to evaluate the culture isolates from neutropenic febrile and non-febrile canine chemotherapy patients.

The study will cover the cost of the blood cultures (2 sets), urine culture, complete urinalysis, and ultrasound-guided cystocentesis charge.

Following owner consent for enrollment in the study, we will collect blood culture and sensitivity samples (aerobic and anaerobic) from two separate sites and a urine sample for complete urinalysis and urine culture& sensitivity. We will be using ultrasound-guidance to obtain urine via cystocentesis; when there is a contraindication to cystocentesis (thrombocytopenia or previously diagnosed urinary bladder neoplasia), we will collect a midstream voided urine sample.

Exclusion criteria: Previous enrollment in this study OR Packed cell volume (PCV)<20%.

Please contact Dr. Jessica Diaz or Dr. Jonathan Bach if you have any questions about the study or study enrollment 608-263-7600.

Oncology Clinical Trials

For additional information regarding any of these oncology studies, please contact Dr. Mairin Miller or members of the Oncology Service at (608) 263-7600.

DOGS WITH NEWLY DIAGNOSED OR RECURRENT LYMPHOMA

This clinical trial sponsored by the National Cancer Institute (NCI) assesses the safety and effectiveness of three newly developed chemotherapy agents (Indenoisoquinolines) when given to dogs with lymphoma. Studies in mice and non-tumor-bearing dogs have shown indenoisoquinolines to be safe.

The study involves intravenous administration of an indenoisoquinoline daily for 5 consecutive days. Blood samples, bone marrow biopsies, and tumor biopsies will be collected prior to treatment and following the first and fifth treatment. The first week of this study will necessitate some (minimum of 2 nights) if not all, overnight boarding at the VMTH. Dogs will then return weekly for re-evaluation and subsequent blood collection (Day 8, 15, 22 and 29). Continuance on study beyond day 29 will be based on response to indenoisoquinoline therapy. Costs associated with this study will be provided by the study. In the event any complications arise during the study period, their management will be covered by study funds up to $2000/per dog/per event. This would include any unanticipated hospitalizations. In addition, a gift of $1,000 (one thousand dollars) will be credited to the owner's VMTH account.

DOGS WITH CUTANEOUS T CELL LYMPHOMA

The most common type of lymphoma in dogs is multicentric, meaning it involves several lymph nodes. A less common type of lymphoma, called cutaneous T cell lymphoma (CTCL), presents as tumors in the skin. While dogs with multicentric lymphoma initially respond to currently available chemotherapy protocols, response rates are considerably lower and generally briefer in duration in patients with CTCL. We previously demonstrated the effectiveness of the novel chemotherapy agent GS-9219 in dogs with multicentric lymphoma in which 100% of newly diagnosed dogs and 60% of previously treated (with chemotherapy drugs other than GS-9219) dogs experienced antitumor responses. One of the observed toxicities in GS-9219-treated dogs was a skin reaction characterized by redness, hair loss, and itching, implying significant delivery of GS-9219 to the skin. Given the lack of effective therapy for canine CTCL and the demonstrated anti-lymphoma activity and apparent skin accumulation of GS-9219, we are evaluating the effectiveness of GS-9219 in canine CTCL. GS-9219 will be administered as a 30-minute intravenous infusion once every 21 days. The owner will be responsible for the costs of the initial examination and tests to insure eligibility to participate (approximately $400). Costs associated with this study will be provided by the study. In addition, a gift of $500 (five hundred dollars) will be credited to the owner's VMTH account.

DOGS WITH ANY MALIGNANT TUMOR

Doxorubicin is an effective chemotherapy drug commonly used for the treatment of various cancers in dogs including lymphoma, hemangiosarcoma, and osteosarcoma. The lifetime dose of doxorubicin is limited due to its cardiac toxicity, which limits the longterm use of this drug. Doxil®, a doxorubicin containing liposome, has been shown to decrease cardiac toxicity, prolong drug circulation times, and enhance anticancer effects (when compared to free doxorubicin). However, unlike free doxorubicin, a skin reaction (ranging from mild redness and hair loss to severe crusting, ulceration, and peeling of the skin) termed Palmar-Plantar Erythrodysesthesia Syndrome (PPES) or hand-foot syndrome can be dose-limiting for Doxil® in both dogs and people and often prevents repeated dosing. A new formulation of a doxorubicin containing liposome, called PLDMS, has been found to have increased anticancer activity and a reduced incidence of PPES when compared to Doxil®. The purpose of this study is to determine the maximum tolerated dose in dogs and compare the incidence of PPES to dogs in a previous study that had received Doxil®.

This trial is scheduled to open in early May 2012. Dogs with any measurable malignant tumor may be eligible for this study. The study involves intravenous administration of PLDMS once every 3 weeks for a total of 5 treatments. At the time of each treatment, blood and urine tests, and a skin biopsy will be performed. One week after each treatment, a blood test will be performed. The owner will be responsible for the costs of the initial examination and tests to insure eligibility to participate (approximately $400). Costs associated with this study (all treatments and follow-up examinations and procedures) will be provided by the study. In the event any drug-related complications arise during the study period, their management will be covered by study funds up to $3000/per dog. This would include any unanticipated hospitalizations.

DOGS WITH ANY MALIGNANT TUMOR

Computerized tomography (CT) is a commonly used diagnostic tool which provides information regarding the presence of tumors often too small to detect using conventional X-rays. Contrast agents that preferentially bind to tumors are often administered just prior to a CT scan to further enhance the chance of detecting a tumor. One of the limitations of currently used contrast agents is their short half-life, disappearing from the body within hours of administration. A contrast agent that remains in the body longer (for several days without adverse effects) would allow for the performance of multiple CT scans over time which could provide valuable information regarding the effectiveness of anticancer treatments. The purpose of this study is to evaluate a novel imaging agent that has a half-life of at least 24 hours, allowing for the performance of multiple CT scans over time following a single injection, and has been found to provide greater resolution of the CT images which may increase the ability to detect tumors at an earlier stage of development. This is extremely important with regard to the ability to detect metastatic lesions in patients diagnosed with cancer and for the evaluation of the effect of their cancer treatment.

Dogs with any metastatic malignant tumor for which the owner has elected treatment or euthanasia may be eligible for this study. The study involves the performance of 3 CT scans; one prior to administration of the contrast agent, and then again at one and 24 hours after intravenous administration of the contrast agent. The study will cover all costs associated with the performance of the CT scans and, in addition, $1,000 will be credited to the owner's VMTH account if the dog will be undergoing treatment or $500 will be credited to the owner's VMTH account if the dog will be euthanized following completion of the CT scans.

DOGS WITH A MALIGNANT MAMMARY TUMOR, MELANOMA, HEAD AND NECK CARCINOMA, OR SOFT TISSUE SARCOMA

The purpose of this study is to assess the safety and effectiveness of iniparib, a novel anticancer agent, in combination with one dose of carboplatin, when given to dogs with cancer. Iniparib has been safely evaluated in human patients with cancer and in normal, non-tumor-bearing dogs. Carboplatin is a commonly used chemotherapy drug for the treatment of cancer in dogs.

Dogs that have been diagnosed with a new or recurrent malignant mammary tumor, melanoma, head and neck carcinoma, or soft tissue sarcoma may be eligible for this study. Dogs will be excluded from this study if they have had any prior therapy for their cancer other than surgery. The study involves four intravenous administrations of iniparib over the course of 22 days and one intravenous administration of chemotherapy (carboplatin) study day 8. Tumor biopsies will be performed prior to starting treatment and then once following each iniparib treatment. Additionally, a physical examination will be performed and a blood sample will be collected prior to starting treatment and then again on study days 1, 4, 8, 11, 15 and 22. After Day 22, dogs will be off study and eligible to pursue other treatments and therapies. Costs associated with this study will be provided by the study. In the event any complications arise during the study period, their management will be covered by study funds up to $2000/per dog/per event. This would include any unanticipated hospitalizations. In addition, a gift of $1,000 (one thousand dollars) will be credited to the owner's VMTH account.

DOGS WITH NASAL TUMORS

Tomotherapy clinical trial for dogs with nasal tumors: Conformal avoidance of eyes and brain.

Helical TomoTherapy™ is a combination of a linear accelerator and a helical CT scanner that delivers highly precise radiation to treat tumors while avoiding critical normal tissues. This radiation therapy machine was developed at the University of Wisconsin. In a previous study the UW-SVM treated 31 dogs with nasal tumors delivering dose to the tumor while avoiding the eyes, which significantly reduced ocular toxicity. In this new study we are evaluating molecular imaging of the tumor to guide and individualize each dog’s treatment plan with the goal to prolonging overall survival. Owners are responsible for the cost of the initial staging (approximate cost $1000-1200). Owners will pay $1500 toward this state-of-the-art therapy (typical cost is $4500-5000) and owners will pay for medications.

The study will pay for the following:

Radiotherapy treatment with Helical TomoTherapy™ & anesthesia
Molecular imaging (PET/CT’s), tumor biopsy correlated with imaging, & anesthesia
Ophthalmic exams and CBC/serum biochemistry profile/urinalysis
Hospitalization during treatment and imaging

DOGS WITH MAST CELL TUMORS

Mast cell tumors (MCT) are a common skin tumor of dogs. Current treatment options available for MCT include various combinations of surgery, chemotherapy drugs such as vinblastine or lomustine, radiation therapy, and the new oral MCT drug Palladia® (toceranib). We currently have two clinical trials for dogs with MCT:

In the first trial, we are seeking to investigate the difference in responses of MCT with and without a mutation in KIT to Palladia and vinblastine. Vinblastine is an intravenous chemotherapy agent that is commonly used in the treatment of MCT. Palladia is an oral drug which works by inhibiting the function of a protein important for mast cell survival called KIT. Activating mutations in KIT are found in a population of MCT, and Palladia has been shown to be more effective against tumors with this mutation. Dogs with confirmed MCT, with or without lymph node involvement, may be eligible for this study. Prior surgery for MCT is acceptable, but no previous medical therapy (steroids, chemotherapy, etc.) is permitted. Upon entry, dogs will be randomized to receive either Palladia or vinblastine. The study will pay for the initial biopsy, KIT genotyping (to determine mutation status), chemistry profiles, and costs associated with treatment (Palladia or vinblastine). The owner will be responsible for the costs of the initial examination and tests to insure eligibility to participate (approximately $400), the recheck examinations, complete blood counts, and ancillary medications (Benadryl, omeprazole, prednisone).
In the second trial, we are investigating the combination of Palladia and lomustine. Dogs with confirmed MCT, with or without lymph node involvement, may be eligible for this study. Prior surgery and chemotherapy for MCT is acceptable with the exception of prior treatment with Palladia or lomustine. Dogs that have received Palladia or lomustine are not eligible for this study. All dogs will receive Palladia and lomustine. The dose of lomustine will be increased as dogs are entered into this trial so that we can determine the maximum tolerated dose of lomustine when given in combination with Palladia. The study will pay for the costs associated with treatment (Palladia and lomustine), and physical examinations and blood tests required throughout treatment. The owner will be responsible for the costs of the initial examination and tests to insure eligibility to participate (approximately $400) and ancillary medications (Benadryl, omeprazole, prednisone).
In this third trial, we are investigating a novel anticancer agent which has been shown to have activity in a previous study in pet dogs with naturally occurring tumors. In this study, we will be comparing 4 dosing regimens in dogs with MCT. Dogs with a measurable confirmed MCT that have not received prior chemotherapy (with the exception of prednisone) or radiation therapy may be eligible for this study. Dogs will be randomly assigned to one of 4 dosing regimens and each dog will undergo a total of 4 treatment cycles. The duration of the study is 29 days starting at the time of the first treatment. The owner will be responsible for the costs of the initial examination and tests to insure eligibility to participate (approximately $400). Costs associated with this study (all treatments and follow-up examinations and procedures) will be provided by the study.

DOGS WITH OSTEOSARCOMA

Osteosarcoma (OSA) is the most common bone tumor in dogs. Treatment involves amputation of the affected limb followed by chemotherapy. However, approximately 90% of dogs with OSA will die of spread of disease, usually to the lungs, within 2 years of amputation despite aggressive therapy. If significant improvements in survival time are to occur, new therapeutic approaches need to be explored. Piroxicam is a non-steroidal anti-inflammatory drug that is thought to help inhibit blood vessel growth in tumors by blocking an enzyme called COX-2. Cyclophosphamide is a chemotherapy agent that when given at a very low dose is thought to inhibit the growth and migration of new blood vessel cells. Palladia is a new anticancer drug approved for use in dogs that works by blocking the signaling of several receptors, including ones that control the growth of new blood vessels in tumors. There is evidence that combinations of these drugs may be more effective than giving these drugs alone. The purpose of this study is to compare the combination of piroxicam and cyclophosphamide, with or without Palladia, in dogs with OSA following amputation and standard of care treatment consisting of 4 cycles of carboplatin. The study will pay for the carboplatin (total savings of approximately $600-800). The owner will be responsible for all bloodwork, chest x-rays and clinic visit charges during the 4 visits for carboplatin administration. Following initiation of the piroxicam/cyclophosphamide or Palladia/piroxicam/cyclophosphamide maintenance therapy, the owner will be responsible for the piroxicam and cyclophosphamide costs (approximately $50/month) and the costs associated with recheck visits. However, the owner will receive a credit at each recheck visit (approximately $50-75/visit) following initiation of oral therapy totaling $650 over 8 months.

DOGS WITH MALIGNANT MELANOMA

Malignant melanoma is a highly aggressive cancer that is resistant to standard chemotherapy. Surgery and/or radiation therapy may control the primary tumor, but most dogs die within one year. Tyrosine kinases are proteins that play a key role in regulation of cell growth. Evidence suggests that in humans and companion animals, tyrosine kinases are often abnormally activated leading to uncontrolled cell growth. Masitinib is a tyrosine kinase inhibitor that has been found to prolong the time to disease progression in dogs with mast cell tumors. The purpose of the proposed study is to evaluate the antitumor activity of masitinib when given alone or in combination with currently available treatments for dogs with melanoma. In the proposed studies, dogs with melanoma will be randomized to receive masitinib alone, Oncept (Canine Melanoma Vaccine) alone, or masitinib combined with the chemotherapy drug doxorubicin. The cost of masitinib, Oncept, and doxorubicin will be paid for by the study. Owners are responsible for the cost of the initial staging (approximately $400-600), blood and urine tests, and examination fees.

DOGS WITH T-CELL LYMPHOMA

Lymphoma is one of the most common cancers in dogs. Most affected dogs present with enlarged lymph nodes. While lymphoma is responsive to chemotherapy, with more than 80% of dogs achieving complete clinical remission of more than one year, the type of cell involved (T-cell or B-cell) affects prognosis. Dogs with T-cell lymphoma have a poorer prognosis as these cells are more resistant to chemotherapy and remission times are shorter than for dogs with B-cell involvement. Recent laboratory observations suggest that the tyrosine kinase inhibitor, masitinib (discussed above under Malignant Melanoma) may enhance the anti-tumor activity of chemotherapeutic agents. Dogs with confirmed T-cell lymphoma will be eligible for this study and will be randomized to receive either masitinib alone, doxorubicin alone, or a combination of these agents. The cost of masitinib and doxorubicin will be paid for by the study. Owners are responsible for the cost of the initial staging (approximately $400-600), blood and urine tests, and examination fees.

OFFSET THE COST OF BIOPSY FOR DOGS WITH LYMPHOMA, OSTEOSARCOMA, ORAL MELANOMA, MAST CELL TUMOR, PRIMARY LUNG TUMOR, OR HEMANGIOSARCOMA

We were one of the first three centers nationally (there are now 7) to become a cancer tissue procurement center for the Canine Comparative Oncology and Genomics Consortium (CCOGC), a group of veterinary and medical researchers who have determined that a well-described repository of canine tumor tissues is an essential resource to progress new cancer therapies. This new resource to fight cancer has been named the Pfizer Inc. CCOGC Biospecimen Repository (www.ccogc.net). The cost of surgical biopsy collection, a necessary diagnostic step in the majority of patient work-ups, is completely covered in most cases (unless involving open cavity collection).

For additional information regarding any of these oncology studies, please contact Dr. Mairin Miller or members of the Oncology Service at (608) 263-7600.

DOGS: Incidence of bacterial infections in Febrile and Afebrile neutropenic patients undergoing chemotherapy

Inclusion criteria: For this prospective observational study, we are enrolling current canine chemotherapy patients with<1500 neutrophils/uL.

The purpose is to evaluate the culture isolates from neutropenic febrile and non-febrile canine chemotherapy patients.

The study will cover the cost of the blood cultures (2 sets), urine culture, complete urinalysis, and ultrasound-guided cystocentesis charge.

Exclusion criteria: Previous enrollment in this study OR Packed cell volume (PCV)<20%.

Please contact Dr. Jessica Diaz or Dr. Jonathan Bach if you have any questions about the study or study enrollment 608-263-7600.

Ophthalmology Clinical Trials

The Enucleation Pain Study

What are we doing? The University of Wisconsin is performing a study on postoperative pain management in dogs undergoing eye removal surgery (enucleation).

Why are we doing it? Almost every week a dog undergoes enucleation surgery at the University of Wisconsin. We want them to get the best pain control possible. We are testing how effective an oral non-steroidal anti-inflammatory versus a synthetic oral opioid medication is at controlling postoperative pain.

What would happen to my dog? Dogs that qualify for the study would be randomly assigned to a group that receives either an oral non-steroidal anti-inflammatory or an oral opioid. All dogs in the study will need to stay the night before and the night after surgery.

Are there any risks? The procedure we are testing is safe and simple. As with all anesthesia, there is a risk of an allergic reaction. If your dog is painful after surgery, we will provide additional pain medication so you don’t need to worry that your dog will suffer.

Is my dog a candidate? Your pet will not be a candidate for this study if the remaining eye is painful, if they have a chronic painful condition for which he or she is taking daily medication (i.e. Rimadyl), underlying kidney and/or liver disease, or if you are unable to leave your pet hospitalized for 30 hours post operatively.

Will I be compensated for my participation? In addition to contributing to the science of ophthalmology, study participants will receive a discount on the surgical procedure and free hospitalization (approximately $400 dollars compensation).

Call the ophthalmology department at 608-263-7600 for more information.

Small Animal Internal Medicine Clinical Trials

Sulfa Drug Allergy Study

Have any of your canine patients been treated with sulfa antibiotics? We are looking to obtain blood samples from dogs that have been treated with potentiated sulfonamide antibiotics. We are interested in dogs that have had uneventful treatment, as well as those with suspected adverse reactions (dry eye, skin eruptions, liver toxicity, thrombocytopenia, joint inflammation, or fever). We are looking for drug-specific T cells and genetic markers of sulfonamide hypersensitivity.

Eligibility: Dogs of any age that have been treated for at least one week with either Tribrissen, Primor, or human generic sulfa drugs (trimethoprim-sulfamethoxazole).

Protocol:

Obtain verbal client consent
Draw 6-10 ml blood in heparin
Keep sample at room temperature
Blood must be shipped overnight the same day that blood is drawn
Email Eva Bachar ebachar@wisc.edu or Lauren Trepanier latrepanier@vetmed.wisc.edu to obtain a FedEx stamp for free shipping.

Thank you for your help!

If you have study questions, please contact Dr. Lauren Trepanier Office: 265-9022; email: latrepanier@vetmed.wisc.edu

NEEDED: DOG WITH SUSPECTED IMMUNE MEDIATED POLYARTHROPATHY or FEVER OF UNKNOWN ORIGIN

STUDY: We are beginning a study to evaluate surrogate markers of inflammation in dogs with immune mediated polyarthropathy (IMPA). IMPA is a common cause of fever of unknown origin and typically causes signs of lameness, joint effusion, lethargy, and anorexia. Diagnosis and monitoring this disease requires arthrocentesis and sedation, which can be technically challenging, expensive, and not without risks to the patient. The overall goal of the study is to identify a surrogate marker of inflammation that correlates with clinical and cellular improvement of polyarthropathy. This marker may possibly be used to monitor treatment efficacy and diagnose relapse of IMPA. Dogs will have force plate analysis and wear an accelerometer attached to their collar to assess lameness and mobility.

DOGS: Our target population is dogs with naturally occurring IMPA who have negative antibody titers for Borrelia, Anaplasma, and Ehrlichia (Idexx 4DX negative). Dogs will undergo the standard baseline workup for IMPA (CBC, biochemistry, urinalysis, joint radiographs and arthrocentesis). Additionally, all dogs will have kinetic force plate analysis performed and be fitted for an accelerometer to be worn on their collar for the duration of the study. This initial work-up will be performed at the VMTH. An additional 6 mls of blood will be used for the study. Dogs will be treated with a standard protocol of Prednisone. Recheck examinations will occur 2 and 4 weeks later at the VMTH, during which repeat arthrocentesis and force plate analysis will be performed and 5 mls of blood will be obtained to quantify markers of inflammation.

CLIENT INCENTIVE: The advantage to the client is that their dog will receive initial joint radiographs, and recheck appointments and diagnostics (internist exam, complete blood count, biochemical panel, urinalysis, force plate analysis, arthrocentesis, and synovial fluid analysis) at no cost.

Please contact Dr. JD Foster (608-263-7600) or Dr. Lauren Trepanier (608-265-9022) with any questions regarding the study.

Female Dogs with Uncomplicated Urinary Tract Infections Needed for Study

The University of Wisconsin-Madison School of Veterinary Medicine (VMTH) is enrolling patients in a clinical trial investigating the clinical and microbiological cure rates in female dogs with uncomplicated urinary tract infections by comparing conventional therapy (10 days of penicillin-type antibiotic) to short-course (3 day) trimethoprim-sulfamethoxazole.

The Internal Medicine Service will evaluate dogs that are potentially eligible for the study. Lab work, Schirmer tear test (STT), urinary tract imaging, urinalysis, and urine culture will be performed at enrollment. If eligible, patients will be assigned to one of two treatment groups (10 day course of cephalexin or a 3 day course of trimethoprim-sulfamethoxazole [followed by 7 days of placebo]) in a double-blinded and randomized manner. Clients will be contacted via phone call to assess clinical response after 3 days of therapy. The trial will require 3 follow up outpatient visits over a 1 ½ month period for examination, urine culture, and STT. Rescue therapy will be available at all times for dogs that do not show an adequate clinical response.

To determine if a patient is eligible for this study, please contact Dr. Sharon Clare or Dr. Katrina Viviano (Internal Medicine) at (608)-263-7600. Alternatively, send an email to saim@vetmed.wisc.edu for more information or to schedule an appointment.

URINARY INCONTINENCE IN FEMALE DOGS

We have observed resolution of urinary incontinence in canine patients supplemented with taurine. Taurine functions as a neurotransmitter within the nervous system. Objectives of this clinical trial are to determine if taurine is effective in achieving improvement in continence in spayed female dogs with urinary incontinence. Twenty percent of spayed female dogs will develop some degree of incontinence due to USMI, or urinary sphincter mechanism incontinence. Two medical therapies are available to improve the symptoms of urine leaking, but these treatments are often not 100% effective and side effects can occur. For study questions please contact Dr. Sharon Clare or Dr. Heidi Kellihan at 608-263-7600, or email saim@vetmed.wisc.edu.

Orthopedic Surgery Clinical Trials

Labrador Retrievers Needed For Clinical Trial

The Orthopedic Service is looking for Labrador Retrievers 8 years old or older with no history of cranial cruciate ligament injury in their stifles. If the dog qualifies for the trial we will obtain the following:

Blood sample (2cc in EDTA tube)
Standing radiographs of both stifle joints. This technique DOES NOT REQUIRE SEDATION, and is very quick. The dog will be in a natural standing position while we obtain the images.

There are no costs associated with this assessment. In order to find out if the dog qualifies for this study, please contact:

Krista Carlson, DVM

Email: kjcarlson3@wisc.edu

This study is looking at the potential underlying DLA-DRB1 genetic predisposition in Labrador retrievers for cranial cruciate ligament rupture.

Last updated 4/10/12