If your dog has been diagnosed with cancer of the head (including neoplasias of the oral and nasal cavity and brain), he or she may be eligible to participate in our study. This study is looking at the development of sores in the mouth (oral mucositis) that result as a side effect of radiation treatment. The purpose of this clinical research project is gather data about the development and progression of oral mucositis and how it affects dogs’ behavior and quality of life. After the data is collected, the results will be analyzed in the hope to develop more treatment options and relief for this condition.
Oral Mucositis (OM) is redness, inflamation or open sores inside the mouth and/or throat, caused by radiation therapy in the treatment of cancer. Up to 90% of patients receiving radiotherapy for the treatment of cancer of the head or neck will develop OM. OM causes pain and discomfort, leading to difficulties eating and swallowing, and interferes with sleeping, which can decrease the patient’s quality of life. It may also limit the amount of radiotherapy the patient can tolerate, which may decrease the ability to cure the cancer. Dogs develop OM in much the same way as people do who are being treated for head and neck cancer. The overwhelming similarities between OM in people and dogs suggests that studying OM in dogs may be useful in developing prevention and treatment models for humans.

Eligibility:
Dogs who have been diagnosed with cancer located in any structure in the head (mouth, nose, brain) . Dogs with cancer of the neck (thyroid tumor, etc) are not eligible for the study at this time.
You have elected to pursue radiation therapy to treat your dog’s cancer

You must be able to bring your dog to the hospital for his or her scheduled radiation treatments as determined by the veterinarian and for weekly visits for four weeks following his or her final treatment. You will also be asked to fill out questionnaires at each visit asking about your dog’s quality of life, general pain and mouth-related pain.
All radiation treatments and related anesthesia, bloodwork and x-rays will be paid for by the study. It is your responsibility to obtain and pay for the initial cancer diagnosis, usually achieved by CT scan.

Lymphoma is a cancer of white blood cells that occurs commonly in dogs. Chemotherapy is used to treat lymphoma and about 85% of dogs respond well to this treatment. However, the majority of dogs will relapse with clinical disease within one year of diagnosis and treatment. One potential reason for disease recurrence is the presence of drug resistant lymphoma cells that are not killed by chemotherapy. Researchers at Penn Vet have identified an aberrantly active, intracellular pathway within lymphoma cells that promotes cancer cell survival and proliferation. Results of a pilot clinical trial have shown that blocking this pathway using a drug known as NBD peptide can promote cancerous cell death.

This clinical trial expands on our previous pilot study and aims to determine whether NBD peptide can

inhibit aberrant pathway activity and kill cancer cells in dogs with B-cell lymphoma
improve short and long term outcomes in dogs with lymphoma

Inclusion Criteria
Your dog is eligible to participate in this clinical trial if:

they have been diagnosed with diffuse large B-cell lymphoma
they have relapsed with the disease OR are newly diagnosed
If the dog is relapsed, they have not received chemotherapy at least 3 weeks prior to screening. If newly diagnosed, they have not yet received any chemotherapy treatment
they have NOT received prednisone or other systemic steroids within the past three weeks
they are otherwise healthy with no major organ disease
they have evidence of an active NF-kappaB pathway within their malignant lymph node (to be determined at screening visit)

Exclusion Criteria
Your dog is not eligible to participate in this study if :

they have T cell lymphoma
they do not have constitutively active NF-kappaB activity in their malignant lymph node
if they are systemically unwell

Benefits:
There is no fee to participate in this study. All study procedures (including blood work and lymphoma immunophenotyping) plus study medication (NBD peptide and antibiotics) will be provided at no cost.
The study will pay for a single dose of standard chemotherapy
The potential benefits could include increased responsiveness to chemotherapy leading to remission and prolonged remission times in patients receiving the NBD peptide

Purpose of the Study:
We are investigating whether an antibody that specifically targets a particular receptor on the surface of malignant B cells could be used to treat dogs with B cell (non-Hodgkin’s) lymphoma. Many types of lymphoma have this receptor on their surface at high levels, a property that makes them stand out from normal immune cells in the body. An antibody targeting this receptor (known as IMMU-114) has recently been developed and is being investigated as a possible new treatment for both humans and dogs with B cell lymphoma. We have tested this antibody in normal, healthy dogs and found that it is safe as long as it is given slowly as an intravenous infusion during an overnight hospital stay. We are now ready to begin evaluating the antibody in dogs with lymphoma so that we evaluate its potential efficacy in treating this common disease.

Patient Entry Criteria:
Dogs with suspected B cell lymphoma may be eligible for the study. Dogs should be otherwise in good health and must have adequate organ function as determined by blood work and urinalysis. To determine eligibility, some of your dog’s tumor cells will first be collected through a needle aspirate of an enlarged lymph node. The cells will be examined to confirm that your dog has B cell lymphoma (rather than T cell) and tested to see if the antibody will recognize your dog’s tumor cells. Previous treatment is allowable provided that dogs have not received any chemotherapy or radiation therapy in the previous 1 week or corticosteroids in the previous 72 hours.

Owner Responsibilities:
You are responsible for the cost of the diagnostic tests required to determine your pet’s eligibility, include cytology of a lymph node aspirate and blood work and urinalysis. You are expected to make and keep all appointments according to the study protocol and all other costs once the study has been completed.

Financial Incentives:
Clients participating in this clinical trial will be given special financial considerations. Once your dog has qualified for this trial, the study will pay for immunophenotyping to determine if B-cell lymphoma, recheck blood work (complete blood count and biochemical profile) and urinalysis, and hospitalization directly associated with antibody administration. The cost to treat any side effects related to the antibody treatment that occur within 7 days after the antibody was given will be covered by the study. In addition, a $400 credit which will be applied to your pet’s account at the CSU Veterinary Teaching Hospital.

The purpose of this study is to evaluate the efficacy of Tavocept in preventing drug-induced toxicity (especially nephrotoxicity) associated with cisplatin and piroxicam therapy for canine bladder cancer and to demonstrate that administration of Tavocept prior to cisplatin chemotherapy in tumor-bearing dogs facilitates the safe use of a shortened diuresis protocol as is the case in people. The overall study goal is to develop a safer (non-nephrotoxic) and more efficacious treatment regimen for dogs with TCC of the urinary bladder by the use of the novel cytoprotective and antitumor potentiating agent, Tavocept.

Criteria:

Measureable confirmed TCC of the urinary bladder
No previous chemotherapy, radiation therapy or excisional surgery for TCC
NSAID’s must be discontinued for at least 14 days prior to study enrollment
Adequate renal function-normal creatinine and BUN on VMTH panel and adequate urine specific gravity.
No serious or life –threatening concurrent disease reducing life expectancy to < 16 weeks
PCV > 25%, neutrophil count > 2500/ul, platelet count > 100,000
Initial: CBC, UA, chem. panel, fecal occult blood, thoracic rads, abdominal ultrasound/rads, abdominal CT.

Therapy and Monitoring:

Tavocept infusion over 45 mins, 30 mins into Tavocept infusion patient will begin 20 minute normal saline diuresis, followed by cisplatin infusion over 20 minutes, then another 20 minutes of normal saline diuresis.
Treatment will be scheduled every three weeks, with a total of four treatments planned.
Piroxicam will be administered beginning on Day 1 and continue throughout the study
CBC and creatinine to be checked 7 days post chemo administration. CBC and renal panel checked prior to each subsequent therapy.
Tumor response will be assessed on day 42 (+/- 2 days) and day 84 (+/- 2 days) with full staging including abdominal CT and US.

Benefit:

Treatment provided at no cost to the owner. Owner to pay for fecal occult blood. This includes initial staging and follow-up CT scans and abdominal ultrasounds, blood work done at the VMTH, radiographs, chemotherapy, hospitalization and subsequent office visits at recheck exams.

Artemisinin-LSA study-The purpose of this study is to evaluate the ability of artemisinin to down regulate genes that cause resistance to chemotherapy, and evaluate response to doxorubicin chemotherapy and artemisinin together as compared to a doxorubicin/placebo combination.

Criteria:

Confirmed B cell multicentric, Stage IIIa or IVa lymphoma
Complete staging including CBC, chemistry panel, flow cytometry, abdominal U/S, BMA, study echo and thoracic radiographs at first visit.
No previous chemotherapy including prednisone.
No cardiac, renal or hepatic insufficiency
Owners must consent to a necropsy if patients dies or is euthanized during course of the study.
Patients will undergo two separate lymph node biopsies, one prior to artemisinin or placebo administration and another three days later.
Owners are expected to keep a drug log to record administration for duration of the study

Therapy:

Twice daily oral medication of either artemisinin or placebo for the duration of the study
Doxorubicin (30mg/m2) every 3 weeks for a total of three treatments.
CBC prior to and one week after each scheduled chemotherapy
Monthly rechecks for the duration of the study.

Benefit:

Once enrolled study is fully funded. Treatment includes: Sample collection, free drug and drug administration, blood work, re-evaluating disease burden and office calls.
Owner is responsible for diagnosis and staging, if accepted into the study owner will only pay first $300.00 of staging.

Inclusion Criteria and General Background Information: Your dog must have a confirmed diagnosis of melanoma and several tests to ensure his/her general health and to assess how advanced the disease is prior to treatment. The tumor will be biopsied prior to therapy. Tumors must be large enough to biopsy and your dog must have no other significant health problems.
Exclusion Criteria: Dogs with significant concurrent disease are excluded from this study. Dogs cannot be receiving concurrent chemotherapy (including corticosteroids) or radiation therapy. Dogs must be off of all such therapy for 3 weeks prior to study enrollment. No dogs under 15 kg (<33 lbs) will be allowed in this study.
Owner Commitments: Prior to entry into this study, your dog must have a confirmed diagnosis of melanoma and staging tests to ensure his/her general health and to assess how advanced the disease is. The tumor will need to be biopsied before therapy for this purpose. Your dog will receive one of two drugs or a combination of the two. Both drugs are FDA approved and have been used in dogs previously for other reasons. Interactions between these drugs and other drugs are unknown; therefore it is important to tell your veterinarian about any medications (and supplements) your dog is currently taking. It is strongly encouraged to eliminate all unnecessary medications. This should be discussed with your oncologist if you have any questions.
Financial Incentives: All costs associated with this study will be provided as part of your participation. In the event any complications arise during the twenty-nine (29) day study period (time period between drug administration and assessment), their management will be covered by study funds up to $1000/dog. This would include any unanticipated hospitalizations. However, all costs exceeding $1000/dog are your responsibility.

Purpose
The goal of this study is to assess efficacy of Palladia and Vinblastine combined for treatment of canine transitional cell carcinoma and to compare computerized tomography and ultrasound for measurement of tumor response.

Background
Canine transitional cell carcinoma (TCC) of the urinary bladder makes up for 2% of all cancers diagnosed in dogs, and is a common cancer found in certain breeds of dogs – Scottish Terrier, West Highland White terrier, Beagles and Shelties. The location of the cancer within the bladder makes surgery often not an option, and the chance of chemotherapy working in this disease is low – only about 30% of dogs respond to treatment and most only experience stable disease for a period of time. Therefore, new treatments are desperately needed for this disease. Another problem encountered in the treatment of this disease is the fact that because the urinary bladder is an organ that can stretch and contract, measuring bladder tumors accurately and assessing whether treatment is working can be difficult. Ultrasound is currently the method most commonly used to measure TCC although it is very difficult to do so accurately using this technique and measurements are often subjective rather than objective. In human cancer therapy, a CT scan is used to measure human bladder tumors and is the standard practice for determining a response to therapy. Therefore, it is likely that CT scan would be more accurate to measure bladder tumors in dogs. The purpose of this clinical trial is to first determine whether a new combination of drugs to treat TCC is more effective than the currently available therapies, and to also determine whether CT will be more accurate in measuring the TCC before and after treatment.

The two drugs to be combined in this clinical trial are vinblastine, a chemotherapy agent used to treat several different cancers in dogs, and Palladia, an oral drug that works by blocking the signaling of several receptors, including VEGFR2 and PDGFR. Both VEGFR2 and PDGFR are important in permitting the growth of new blood vessels, so Palladia works to slow down or block the growth a blood supply into tumors and prevent them from continuing to grow. There is preliminary evidence that both vinblastine and Palladia may each have some activity against TCC in dogs. A recent pilot study demonstrated that 36% of dogs with TCC given vinblastine had their tumor shrink partially following treatment and another 50% had their tumors stop growing for a period of time. In previous work with Palladia, 3 of 4 dogs treated with drug had their tumors stop growing for a period of time. Vinblastine and Palladia have recently been combined together in a clinical trial to determine how best to use these drugs together in the setting of mast cell cancer. This study identified the dose of vinblastine and Palladia that could be safely combined over multiple treatments. These doses will be used in the current study.

Inclusion criteria
To qualify for enrollment in this study, dogs must have:

Measurable TCC of the urinary bladder;
Age > 1 year;
A life expectancy of at least 16 weeks;
No evidence of other illness such as kidney, liver or heart disease;
Not been treated previously with chemotherapy. Previous treatment with NSAIDs and surgery are accepted
Study Design
A total of 10 dogs will be enrolled on this study. Dogs with a diagnosis of TCC of the urinary bladder will have initial tests performed to determine whether he/she is eligible for the study including bloodwork and chest x-rays. If so, then a baseline ultrasound scan, CT scan and cystoscopy will be performed. Once these have been completed, patients will receive vinblastine once every 2 weeks for a total of 8 treatments, and Palladia orally every Monday, Wednesday and Friday for a total of 16 weeks. All dogs will need to return to the Veterinary Medical Center 1 week following the first treatment, then every 2 weeks for a total of 16 weeks for physical examination, bloodwork and to receive the vinblastine treatments. The abdominal ultrasound will be repeated at weeks 4, 8, 12, and 16 of the study (this does not require anesthesia) and the CT scan will be repeated at weeks 8 and 16 of the study (this does require general anesthesia).

Client Compensation
The study will cover the majority of the cost associated with the visits ( around $4500 per patient for the total duration of the study)
Palladia will be provided free of charge for 6 months after the study is completed
Client Cost
Owner is responsible for the initial office visit and screening tests, which is estimated to cost $450
For each treatment visit the owners are responsible for $57 (hospital and recheck fees)

The purpose of this study is to evaluate the safety and tolerability of KPT-335 given on a compassionate use basis to dogs with failed/metastatic lymphoma, mast cell tumor, osteosarcoma, and melanoma

Background
In both normal and cancerous cells, proteins important in regulating cell growth and survival regularly move between the cell cytoplasm and the nucleus (center) of the cell. This shuttling of proteins is tightly controlled and helps to decide which genes get turned on and which genes get turned off. It is known that a specific protein in the membrane of the nucleus, CRM1, controls the shuttling of several key proteins in and out of the nucleus. In fact, over 150 proteins have been found to use CRM1 to leave the nucleus of the cell and enter the cytoplasm. In cancer cells, the function of CRM1 is critical to maintaining the uncontrolled growth and survival of these cells. Recent studies indicate that blocking CRM1 can induce death of cancer cells as they cannot recover function when the shuttling of proteins is disrupted; in contrast, normal cells appear to be less sensitive to this effect, likely because they are not growing in an uncontrolled manner. The novel compound KPT-335 is an irreversible inhibitor of CRM1; that is, once it binds, CRM1 cannot function unless new CRM1 protein is made. Studies in the laboratory have shown that KPT-335 kills a variety of cancer cell lines, even those known to be resistant to chemotherapy. KPT-335 has also demonstrated activity in mouse models of cancer when given by injection under the skin or orally. KPT-335 has also been tested in normal dogs where doses of 3-5 mg/kg were given Monday, Wednesday, Friday (MWF). Mild vomiting, diarrhea, and appetite loss did occur; this recovered with the addition of canned food to the diet and supportive care. In doses above 58 mg/kg, elevations in liver values were observed, although they recovered with discontinuation of drug and the use of a lower dose.

Inclusion criteria
To qualify for enrollment in this study, dogs must:

Dogs diagnosed with lymphoma, mast cell tumor, osteosarcoma, or melanoma. The patient may have failed standard therapy or there may be no other known effective antineoplastic therapeutic options, or the owner may elect to enter the patient in lieu of standard therapy.
Dogs must be at least 1 year of age.
Adequate organ function as indicated by standard laboratory tests
Dogs must have an estimated life expectancy of at least 28 days.
Prior chemotherapy or radiation must be completed at least 2 weeks prior
Owner must be able to orally administer drug according to designated schedule
No evidence of brain metastasis
Can not be less than 2 weeks from a major surgical procedure

Study Design
Patients will be screened for eligibility, if enrolled dogs will be administered KPT-335 orally (PO) Monday and Thursday of each 7 day cycle for a total of 4 cycles.
Drug will be administered on an empty stomach by the owner at home at the same time each morning. Patients will need to return on Weeks 1, 2, 3, and 4. On these days, the patient will need to arrive with in 2 hours of administering medication for blood levels and blood work.
Dogs who respond to KPT-335 treatment with an objective response (CR or PR) or stable disease (SD) according to predefined criteria may continue to receive cycles of KPT-335 indefinitely, as long as DLT is not observed.
Dogs that miss more than 1 dose of a cycle for toxicity may have their dose reduced by 1 level. Any dog requiring a delay in dosing of more than 48 hours due to drug toxicity will also have its dose reduced by 1 level. Patients requiring a dose delay of more than 2 weeks for toxicity possibly, probably, or definitely related to protocol-based therapy will be removed from the study. If a dose is missed or the entire dose is not given, the dose will not be made up.
Client Compensation
The sponsor will cover study associated costs for screening, exam fees, labwork and upto $750 for any adverse events.

The goal of this study is to determine response rates in dogs with mast cell tumors recieving STA-1474 using 4 different dosing regimens.

Background
Heat shock protein 90 (HSP90) is a chaperone protein important in the maintenance of several cellular proteins such as the oncogene Kit. Evidence suggests that its activity is upregulated in cancer cells to maintain appropriate folding and expression of client proteins, particularly when these proteins are over-expressed or mutated. As such, adequate HSP90 activity is considered to be critical for the survival of several types of cancer cells. STA-1474, a novel water-soluble resorcinol-containing compound, is metabolized to STA-9090, a potent HSP90 inhibitor that exhibits superior anti-tumor efficacy relative to HSP90 inhibitors of the geldanamycin class. A Phase 1 trial of STA-1474 was performed in 25 dogs with spontaneous tumors. Measurable responses were observed in dogs with mast cell tumors, osteosarcoma, melanoma and thyroid carcinoma. The greatest biologic activity occured in a dosing cohort that received STA-1474 at 9.5 mg/kg over 8 hours resulting in plasma levels of STA-9090 greater than 50 ng/ml for 12 hours suggesting that long plasma exposures may be associated with greater biologic activity. Given that an 8 hour infusion of STA-9090 in the human clinical setting is not possible, this study seeks to determine whether two consecutive days of treatment with STA-1474 is superior to other regimens with respect to target modulation and response to therapy.

Inclusion criteria
To qualify for enrollment in this study, dogs must have:

a cytologic or histologic diagnosis of MCT.
be at least 1 year of age.
adequate organ function
not have evident of systemic disease
an estimated life expectancy of at least 8 weeks.
not received prior chemotherapy (including Kit inhibitors) or radiation therapy although can have received prednisone
Study Design
Dogs with MCT will undergo screening including complete blood count, chemistry panel, urinalysis and abdominal ultrasound to determine eligibility for the study. A baseline tumor biopsy will then be obtained if your dog is found to be eligible. Your dog will receive standard medications prior to getting STA-1474 to prevent any diarrhea or vomiting. Following the biopsy, your dog will receive STA-1474 on one of four schedules:

a single dose of STA-1474 at 6 mg/kg over 1 hour
6 mg/kg over 8 hours
3 mg/kg over 1 hr for two consecutive days
3 mg over 1 hour twice per week Friday/Monday).
A tumor biopsy will be obtained 24 hrs and 72 hours after the last STA-1474 administration on the first cycle. The treatments will then be repeated for another 3 cycles, although no further biopsies will be performed. If your dog has responded to therapy, then you will have the option of continuing treatment with STA-1474, although the costs for drug administration will not be covered for these subsequent treatments.

Client Compensation
All costs associated with this study are covered by the study including management of any side effects that may occur.

Purpose
Examine the efficacy of toceranib phosphate (Palladia) as a primary and/or adjuvant agent in the treatment of feline oral squamous cell carcinoma

Background
Oral squamous cell carcinomas account for approximately 90% of feline oral tumors and at this time there are no consistently effective treatment options. These tumors are biologically aggressive and locally invasive. Median survival time in untreated cases is approximately 60 days. Radiation therapy or chemotherapy used alone is generally ineffective. Accelerated radiation protocols appear to have some efficacy. The combination of full course radiation therapy with radiation sensitizers or chemotherapy improves the number of cats that respond to therapy, but overall survival times remain in the 4-6 month range. Unfortunately, this treatment option comes with significant expense.

Palladia is a tyrosine kinase inhibitor that affects the development of blood vessels by targeting receptor tyrosine kinases within tumors. By blocking the signaling of these pathways tumor growth can be slowed. The presence of these receptors (VEGF and VEGFRs) has been well documented in human oral squamous cell carcinomas. This has not been evaluated yet in feline tumors. Evidence continues to accumulate indicating that Palladia can also increase the sensitivity of tumor cells to radiation therapy and that Palladia has some primary activity in feline oral squamous cell carcinomas. Because of these effects, clinical investigation of Palladia as therapy for feline oral squamous cell carcinoma alone or in combination with radiation therapy is indicated.

Study Design and Client Compensation
Cats deemed eligible based on prior evaluation will be treated with Palladia (3 to 3.25 mg/kg every other day at the investigator’s discretion). Whether to treat with radiation therapy will be the owner’s decision. Radiation patients will receive 6 radiation treatments over three weeks to a total dose of 36 Gy. Your cat will receive a physical examination, complete blood count, toxicity assessment, and drug accountability weekly for the first three weeks, then at week 5, then at four-week intervals.

Your cat will receive the drug at no cost. We expect that treatment with Palladia will benefit some cats with oral squamous cell carcinoma by increasing response rates and prolonging disease free intervals and overall survival times.