Soft tissue sarcoma clinical trial for cats and dogs.

Study: Exploratory safety study of an intravenous infusion of a novel therapeutic agent for the
treatment of melanoma, osteosarcoma, soft tissue sarcoma or squamous cell carcinoma in dogs

Available at the following locations:
ARIZONA: So uthwest Veterinary Oncology, Gilbert and Tucson, AZ (480-635-1110; 520-888-3177)
CALIFORNIA: Veterinary Specialty Hospital, San Diego, CA (858-875-7500); Veterinary Cancer Group, Culver City, CA
(310) 558-6120
CONNECTICUT: Veterinary Oncology & Hematology Center, Norwalk CT (203-838-6626)
MINNESOTA: University of Minnesota Veterinary Medical Center, Minneapolis, MN (612-626-5786 or 612-626-8387)
NEW ENGLAND: NEVOG, Waltham, MA (781-684-8688)
NEW JERSEY: Redbank Veterinary Hospital, Tinton Falls, New Jersey (732-747-3636)
OHIO: Ohio State University V eterinary Medical Center, Columbus, OH (clinicaltrials@cvm.osu.edu)
VIRGINIA: The Oncology Service, Leesburg, VA 20176 (571-439-6655)
WISCONSIN: University of Wisconsin Veterinary Teaching Hospital, Madison, WI (608-263-7600)

Summary: Dogs must have spontaneous measurable melanoma, osteosarcoma, soft tissue sarcoma, or squamous cell
carcinoma. “Measurable” may be a primary tumor or a metastatic lesion. Dogs that meet the eligibility criteria will be
treated with a single intravenous infusion of the therapeutic agent. Treated dogs will require close monitoring for 6 hours
after treatment with follow-up visits required 2, 4, 7 and 14 days post-treatment. While the patient remains on study,
there will also be rechecks at 1 and 2 months. In some study dogs, medications in addition to the therapeutic agent will
be used.

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

Histologic or cytologic diagnosis of cancer (biopsy or needle aspirate)
There is at least 1 tumor (melanoma, osteosarcoma, soft tissue sarcoma, or squamous cell carcinoma) which can
be measured (minimum 1 cm in diameter)
Generally feeling well (i.e. eating, drinking, ambulating on their own, etc.)
No evidence of an active bacterial infection requiring antibiotics (other than topical medications) in the past 7 days
No anti-cancer therapy within the past 21 days. This includes chemotherapy, radiation therapy, prednisone (or
other forms of corticosteroids), and immunotherapy
No tumors where abscess (infection) would result in major symptoms

Background: Currently enrolling dogs for a nationwide clinical trial to evaluate a novel cancer treatment for measurable
melanoma, osteosarcoma, soft tissue sarcoma, or squamous cell carcinoma. The goal of this therapy is to specifically
target the tumor and induce an inflammatory response. The proposed benefit of such a response is to shrink existing
tumors and reduce or eliminate microscopic cancer cells that may not be visible by standard (or any) means. The
purpose of this study is to assess the safety and potential effectiveness of this therapeutic agent in dogs.

The therapeutic agent is a modified anaerobic bacterium. In previous trials, it has been shown to target the necrotic
center of malignant tumors, leading to tumor regression or stable disease in many of the small mammals tested.
Common side effects include fever, nausea and inflammation. The primary objective of this multi-institutional exploratory
study is to describe the safety and efficacy of three dosages of an intravenous infusion of C. novyi-NT spores, with and
without concomitant therapy, in dogs with spontaneous tumors.

Financial Incentive: The study sponsor will pay for therapeutic agent, diagnostic tests, and follow-up evaluations. In the
event that side effects are noted and attributed to the therapeutic agent, the study will pay for medical management of
the side effects.

Study: A novel form of antiangiogenic therapy in dogs with measurable soft tissue sarcoma.

Available at the following locations:
CONNECTICUT: Veterinary Oncology & Hematology Center, Norwalk CT (203-838-6626)
OHIO: MedVet, Columbus, OH (800-891-9010; radonc.col@medvetohio.com; medonc.col@medvetohio.com)

Summary: An estimated 86 client-owned pet dogs will be enrolled in this Phase II study. The study is a randomized,
investigator-masked, placebo-controlled study in dogs with measurable soft tissue sarcoma. The randomization of active
Test Article to placebo will be 1:1 with a crossover option for dogs in the placebo arm that have disease progression.
The first eight (8) dogs enrolled in the study will be assigned to receive active Test Article in an open label manner and
will have blood samples collected over a period of 24 hours post treatment. Once enrolled, study patients will be
evaluated at Days 14, 28 and every 28 days thereafter until tumor progression occurs.

Eligibility:

Client-owned pet dogs;
Informed owner consent prior to initiation of screening/treatment;
Measurable soft tissue sarcoma (must have at least 1 target lesion ≥ 1cm longest diameter based on physical
exam or ≥ 2cm if measured via thoracic radiographs);
Histological diagnosis of a Grade II or III soft tissue sarcoma (historical biopsies are accepted), excluding
hemangiosarcoma;
Favorable Performance Score 0-1 (based on Modified Eastern Cooperative Oncology Group Performance Score)

Financial Incentive: Study drug, diagnostic tests, and follow-up exams will be paid for by the study sponsor. In the event
that side effects are noted and attributed to the study drug, the study will pay for medical management of the side effects.

COLORADO
Study: Combination liposomal clodronate and CCNU treatment for dogs with malignant histiocytosis
Location: Colorado State University Animal Cancer Center, Fort Collins, CO
Phone: 970-297-4195
www.csuanimalcancercenter.org/liposomal_clodronate_ccnu_mh

Eligibility: Dogs with cytology or biopsy confirmed MH tumor of any site are eligible for this study. No prior treatment with
CCNU is allowed, and washout periods from corticosteroids, other chemotherapy agents, and radiation therapy are
required. Concurrent NSAID therapy is not permitted. Dogs with any serious underlying diseases, including renal
disease, liver disease, autoimmune disease, and chronic infectious diseases, are however excluded from the study. Also,
dogs with very large MH tumors may not be eligible for the study, at the discretion of the clinician.

Summary: Macrophages are immune cells that normally scavenge bacteria and clear a variety of substances (such as
cell debris, bacteria, and foreign materials) from the body. Recent studies suggest that this cell type may actually play an
important role in promoting tumor growth and spread (metastasis). Macrophages may also contribute to the ability of
tumor cells to become resistant to chemotherapy. Therefore, we are investigating the effectiveness of a new compound
that is designed to eliminate macrophages transiently from the body. Canine MH is thought to be a tumor arising from
macrophages and we have found that canine MH cells are susceptible to liposomal clodronate in vitro (see below). The
clodronate drug is administered after being encapsulated within liposomes, which are tiny, spherical particles that are
widely used to deliver various drugs in the body. Bisphosphonates (the family of drugs to which clodronate belongs)
have been used widely in the treatment of bone cancer metastases in people and dogs.

Studies in mice have indicated that treatment with liposomal clodronate can significantly inhibit tumor growth. A recently
completed study in dogs with MH conducted by our group (Hafeman, et al; Cancer Immunol Immunoth, 2009)
demonstrated that liposomal clodronate had anti-tumor activity when administered to dogs with MH. A second drug
(CCNU) is commonly used in the treatment of dogs with MH and most of our MH patients receive CCNU treatment at
some point in their treatment protocol. Recently, we treated two dogs with liposomal clodronate followed shortly by CCNU
treatment. Both of these dogs experienced dramatic and sustained complete tumor regression, which we believe may be
due to a positive interaction between the two drugs. Notably, both dogs had already been treated with CCNU and initially
failed treatment. This suggests that treatment with liposomal clodronate may restore tumor responses to CCNU
treatment. Therefore, the current clinical trial is designed to investigate whether this combination treatment is in fact
more effective for dogs with MH than either drug alone.

Requirements: You are financially responsible for charges associated with staging tests to determine your pet's eligibility
for enrollment in this study. You are expected to make and keep all appointments according to the study protocol. You
must be committed to completing the entire protocol and follow-up examinations. Please do not hesitate to obtain
additional information from your pet's oncology clinician if you do not understand something about the study or your
pet's care and treatment.

Financial Incentives: Once enrolled, the study will pay for the costs of study-related blood work, hospital fees and the
costs of the liposomal clodronate and CCNU.

NORTH CAROLINA
Study: Biopsy sample from dogs with soft tissue sarcoma for genetic analysis
Location: North Carolina State University Small Animal Clinic, Raleigh, NC
Contact: 919.513.8276 or julie_fisher@ncsu.edu

Eligibility: Dogs diagnosed with the following types of soft tissue sarcomas: fibrosarcomas, hemangiopericytomas,
peripheral nerve sheath tumors, liposarcomas, leiomyosarcomas, rhabdomyosarcomas, myxosarcomas and
undifferentiated sarcomas.

Summary: Soft tissue sarcomas are the most common type of solid tumors in dogs. They are locally invasive tumors with
a high local recurrence rate. The metastasis rate is around 25% depending on the tumor type and grade. The
laboratory of Dr. Marlene Hauck is evaluating the genetic changes that are seen soft tissue sarcomas that metastasize
versus ones that do not. Our goal is to identify a gene or protein “signature” to identify those tumors most likely to
metastasize, and ultimately to improve the outcome for dogs with soft tissue sarcomas. A biopsy sample is obtained from
the sarcoma for the genetic analysis. This can occur at NCSU or at the primary veterinarian.

Requirements and Incentives: There is no financial incentive to take part in this study.