Bone cancer (osteosarcoma) clinical trials for dogs.

Study: Impact of Palladia / Piroxicam / Cyclophosphamide maintenance therapy on the survival time of
dogs with appendicular osteosarcoma following amputation and carboplatin chemotherapy.

Available at the following locations:
ARIZONA: So uthwest Veterinary Oncology, Gilbert and Tucson, AZ (480-635-1110; 520-888-3177)
CALIFORNIA: University of California Davis Veterinary Teaching Hospital, Davis, CA (530-752-0125); Veterinary Specialty
Hospital, San Diego, CA (858-875-7500); Veterinary Cancer Group, Culver City, CA (310) 558-6120
COLORADO: Colorado State University Animal Cancer Center, Fort Collins, CO (970-297-419)
CONNECTICUT: Veterinary Oncology & Hematology Center, Norwalk CT (203-838-6626)
ILLINOIS: University of Illinois Cancer Care Clinic, Urbana, IL (Nancy George of the Oncology Service at (217)-244-7789)
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 Veterinary Medical Center, Columbus, OH (clinicaltrials@cvm.osu.edu)
WISCONSIN: University of Wisconsin Veterinary Teaching Hospital, Madison, WI (608-263-7600)

Background: Osteosarcoma is a common tumor of dogs. Current treatment options available for osteosarcoma include
various combinations of surgery, chemotherapy drugs such as carboplatin or doxorubicin, or radiation therapy. Despite
adjuvant chemotherapy given following limb amputation, greater than 90% of patients die of metastatic disease.
Unfortunately, no significant changes in survival times have been achieved over the past 15 years despite modification of
existing chemotherapy protocols.

Preliminary data suggest that in dogs with metastatic OSA, a combination of Palladia, piroxicam, and low-dose
cyclophosphamide significantly prolongs survival beyond the median of 2 months previously reported for dogs with
metastatic disease treated with chemotherapy, indicating that this triple drug regimen may have biologic activity against
OSA. The purpose of this proposal is to perform a randomized clinical trial to determine the impact of Palladia / piroxicam /
cyclophosphamide on the disease free interval and overall survival of dogs when administered following amputation and
carboplatin chemotherapy.

Eligibility: Dogs with appendicular osteosarcoma treated with amputation are eligible for this study. Dogs must undergo
some diagnostic testing prior to starting the study to ensure that they are eligible. They must have good function of liver and
kidneys, have acceptable blood cell counts, and are free of metastasis or other severe underlying disease. Prior radiation
therapy or chemotherapy for osteosarcoma is not allowed. A 72-hour washout period from steroid or NSAID therapy is
required prior to enrollment.

Requirements: Owners are responsible for the cost of diagnosing and staging the dog's osteosarcoma prior to entering the
study (approximately $500-1000) as well as the costs associated with amputation. The owner is expected to make and keep
all appointments according to the study protocol and must be committed to completing the entire study protocol and follow-
up examinations.

Financial Incentives: Clients participating in this study will be given special financial considerations. Carboplatin will be
provided at no cost to the owner. Once carboplatin therapy is completed, Palladia will be provided by the study and certain
pre-determined financial incentives will be given at each recheck visit.

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: Southern Arizona Veterinary Specialty & Emergency Center, Tuscon, AZ (1-877-762-9838; 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.

CALIFORNIA
Study: Canine patients with Osteosarcoma that elect not to receive standard IV chemotherapy
Location: University of California Veterinary Hospital, Davis, CA
Phone: 530.752.0125
www.vetmed.ucdavis.edu/vmth/small_animal/oncology/studies.cfm#osteosarcoma

Purpose: The goal of this study is to evaluate how well low doses of Gemcitabine control the micro-metastatic disease in the
lungs when given as an inhalant.

Eligibility: Any prospective patient must be examined by the VMTH Oncology or Radiation Oncology service veterinarian,
and require the following baseline evaluations at the owners expense before a dog can be considered for enrollment in the
trial:

•Confirmed diagnosis
•Physical examination with weight recorded
•CBC, Chemistry Panel and Urinalysis All within two weeks of enrollment (referring blood work is acceptable as long as it was
run at a commercial lab)
Baseline Evaluation for Eligibility

•Histologically or cytologically confirmed disease
•Amputation
•No visible Metastasis in the Lungs as noted by a radiologist
•Informed owner consent
•Owner must be able to perform treatments at home
•Return once a month for routine bloodwork and Radiographs

Financial Incentives: This study is Fully Funded through donations and grants. Once enrolled, the study will pay for office
exam, routine bloodwork, and radiographs (while on study). Please note, participation from owner is necessary. Owner is
responsible for performing the aerosol treatments at home.

Study: Canine patients with osteosarcoma with confirmed metastasis to the lungs
Location: University of California Veterinary Hospital, Davis, CA
Phone: 530.752.0125
www.vetmed.ucdavis.edu/vmth/small_animal/oncology/studies.cfm#osteosarcoma

Purpose: The goal of this study is to evaluate the efficacy of Ifosfamide IV in addition to aerosolized Gemcitabine in dogs
with relapsed gross metastatic disease.

Eligibility: Any prospective patient must be examined by the VMTH Oncology or Radiation Oncology service veterinarian,
and require the following baseline evaluations at the owners expense before a dog can be considered for enrollment in the
trial:

Confirmed diagnosis

Physical examination with weight recorded
CBC, Chemistry Panel and Urinalysis All within two weeks of enrollment (referring blood work is acceptable as long as
it was run at a commercial lab)

Baseline Evaluation for Eligibility

Histologically or cytologically confirmed disease
Amputation
Visible Metastasis in the Lungs as noted by a radiologist
Informed owner consent
Owner must be able to perform treatments at home.
Return every three weeks for IV treatment of Ifosfamide and bloodwork.

Requirements and incentives: This study is partially funded. The owner will be responsible for the cost of the Ifosfamide
treatment every 3 weeks. The study will pay for every other radiographic evaluation taken while on study. In addition, the
cost of the aerosol Gemcitabine is covered under the study. Owner is responsible for performing the aerosol treatments at
home.

Study: Pathologic fracture risk of tumor-bearing canine antebrachii
Location: University of California Veterinary Hospital, Davis, CA
Phone: 530.752.0125
www.vetmed.ucdavis.edu/vmth/small_animal/oncology/studies.cfm#osteosarcoma

Eligibility: All dogs must be examined by a VMTH oncology, radiation oncology service or soft tissue surgery veterinarian,
and require the following baseline evaluations at the owners expense before a dog can be considered for enrollment in the
trial:

Confirmed diagnosis
Physical examination with weight recorded
CBC, Chemistry Panel and Urinalysis All within two weeks of enrollment (referring blood work is acceptable as long as
it was ran at a commercial lab)

Baseline Evaluation for Eligibility

Histologically or cytologically confirmed disease
Disease in the radius/ulna
Surgery performed by UCDAVIS Soft Tissue Surgery Department
Informed owner consent

Summary: The objective of this study is to measure the reduction in bone strength due to the presence of osteosarcoma in
the radius/ulna of the dog by measuring the force at which these bones break in a mechanical testing device. These
measurements obtained by testing tumor-bearing bones from clinical patients will be compared to measurements performed
in normal bones. Tumor–bearing bones will be obtained from clinical canine patients that are undergoing amputation of the
affected limb as standard of care treatment for their bone tumor, and testing of these limbs will not affect care received by
these patients. Computed tomography (CT) images of these bones will also be obtained, and this study will seek to
correlate calculated CT indices of bone strength with the biomechanically measured bone strength. It is hoped that
correlations found will allow prediction of patients at most risk for pathologic fracture, improve patient selection for current
treatment options such as palliative radiation therapy, and aid in the development of new minimally invasive limb-salvage
procedures.

Procedures:
1) CT of your dog’s forelimbs under general anesthesia BEFORE surgical removal
2) Biomechanical testing of your dog’s amputated limb AFTER surgical removal

Your dog is presenting to the UC Davis VMTH for treatment of a primary bone tumor of the distal radius (end of the front
leg) by forelimb amputation. Amputation is currently the standard of care treatment to remove the tumor with wide margins
with the fewest potential complications. If you agree to allow your animal to participate, he/she will be treated as usual in
terms of his/her clinical workup and staging. At the time your dog is anesthetized for his/her amputation procedure, you
agree to allow us to perform a computed tomography (CT) scan with and without intravenous contrast of your dog’s front
legs (both legs will be done in the same scan) to image the tumor. While CT imaging is commonly performed as part of
surgical planning for other diseases, this is unlikely to specifically benefit your dog as amputation is designed to remove the
tumor with wide margins and CT results are not likely to alter the surgical plan. CT imaging is anticipated to require 30
minutes of anesthesia additional to that required for normal clinical management for the surgical procedure. Amputation of
the limb will be performed as usual, and there will be no further deviations in the clinical care of your dog as recommended
by the Surgery Service. After the limb with the tumor is removed, it will be taken for biomechanical testing. Once
biomechanical testing is completed, the tumor or a portion of it will be submitted for histopathologic analysis as per standard
of care.

Requirements and incentives: CT of Forelimbs and $325 applied toward total cost of your dog’s anesthesia, which covers
the first two hours of anesthesia. This will cover the anticipated time needed to perform the CT imaging (30 minutes) as well
as provide a financial benefit to allowing your pet to participate in this study as the remainder of this time will be applied
toward your dog’s surgical procedure. You will be financially responsible for the charges associated with the clinical care of
your dog beyond the stipend provided.

ILLINOIS
Study: Phase I trial - Development of bone-seeking nanoparticles encapsulating doxorubicin for canine
appendicular osteosarcoma (bone cancer)
Location: University of Illinois Veterinary Hospital, Urbana, IL
Phone: Nancy George of the Oncology Service at (217)-244-7789. Referring veterinarian and/or client calls are welcome.
http://vetmed.illinois.edu/vth/MedServices/ClinicalTrial/PDF/Oncology/MAFNanoparticlerialAnnouncement2009FINALVersion.
pdf

Eligibility: Dogs with suspected or confirmed treatment naïve appendicular osteosarcoma. No existing kidney, liver, heart
disease, or bone marrow disease.

Summary: Osteosarcoma is the most common bone tumor affecting the dog, with approximately 8,000 new cases diagnosed
annually. Conventional therapies for managing osteosarcoma include amputation of the affected limb with concurrent
administration of chemotherapy. For dogs not suitable for amputation, controlling bone tumor pain remains of utmost
importance. Although palliative radiation therapy and intravenous aminobisphosphonates provide some analgesia, their
duration of effect is short-lived. As such, there remains the need for discovering newer and better localized therapies which
will ultimately improve quality of life for dogs diagnosed with appendicular osteosarcoma.

Encouragingly, bone-seeking nanoparticles may provide a new way to locally deliver high concentrations of anticancer
agents directly to the bone tumor microenvironment, while sparing the systemic organs from conventional toxicity. As such, it
is hoped that bone-seeking nanoparticles will eventually have a definitive role for improving treatments in dogs with
osteosarcoma. The first phase of this study is to characterize the local biodistribution and to identify a safe dosage of bone-
seeking nanoparticles encapsulating doxorubicin in osteosarcoma-bearing dogs. (Doxorubicin is a chemotherapeutic drug
already in use without the nanoparticle formulation) This will be achieved by treating dogs with a single dosage of bone-
seeking nanoparticle encapsulating doxorubicin, and evaluating biologic effects as determined by appropriate surrogate
markers.

Treatment: All dogs will be treated with a single infusion of bone-seeking nanoparticles encapsulating doxorubicin. All dogs
will be reevaluated weekly with additional diagnostics (days 7, 14, and 21).All dogs will have their diseased leg amputated at
the Veterinary Teaching Hospital on day 21

Compensation: The study will pay for the following: Initial examination and recheck fees, blood work (initial and weekly
rechecks), imaging studies and hospitalization (initial and weekly rechecks), leg radiographs, oral analgesics for 21 days,
and credit pet owners with $1500.00 for limb amputation. To receive credit of $1500.00 for limb amputation, it is required
that the surgery to be performed at the Veterinary Teaching Hospital 21 days after infusion of bone-seeking nanoparticles.
All other diagnostics for confirming osteosarcoma diagnosis and assessing metastatic disease including thoracic
radiographs and abdominal ultrasound, as well as small miscellaneous charges will be the financial responsibility of the pet
owner.

INDIANA
Location: Purdue University Veterinary School of Medicine, West Lafayette, IN
Phone: Dr. Diane Schrempp/Patty Bonney at (765) 494-1130
http://www.vet.purdue.edu/pcop/clinical.html

A new treatment protocol is being evaluated post amputation with a diagnosis of osteosarcoma (bone cancer)

LOUISIANA
Location: Louisiana State University School of Veterinary Medicine, Baton Rouge, LA
Phone: 225-578-9900
www.vetmed.lsu.edu/clinical_trials.htm

Eligibility: Eligible dogs must have been diagnosed with osterosarcoma (bone cancer) by either cytologically or histologically.
Patients with local, regional, or systemic metastatic disease are eligible for treatment. Patients with an anticipated survival
time without treatment of more than 2 months are required.

Summary: In this study, dogs diagnosed with osteosarcoma are invited to participate. The participant patient will be treated
with amputation, IL-12 and standard chemotherapy treatment. IL-12 administration via electroporation will be performed 2-7
days prior to and 2-7 days post surgery. If you are not satisfied with the outcome, you can withdraw your pet from the clinical
trial anytime. The participant patients will be anesthetized through LSU-SVM anesthesia service for performing the
treatment, including injection of the immune stimulator via electroporation. Needles will be inserted into tumors for injection
and electroporation. The electroporation lasts for less than one second and the whole procedure last for less than 5
minutes once dogs are under anesthesia. A total of two IL-12 administrations via electroporation will be performed. Prior to
both the first and the second IL-12 administration, blood will be drawn for CBC, serum chemistry profile, and cytokine profile
analysis. A follow-up check will be performed one week after the second treatment. Carbplatin (a standard chemotherapy
drug) will be administered every 3 weeks, and a total of five doses will be administered. A follow-up recheck will be
performed every other month after completion of the chemotherapy protocol.

MASSACHUSETTS
Study: Metronomic chemotherapy in dogs with osteosarcoma (bone cancer)
Location: Tufts University Cummings School of Veterinary Medicine, North Grafton, MA
Phone: Kelly Reed, Oncology Liaison; (508) 887-4682
http://cgi.vet.tufts.edu/clinical_trials/projects/metronomic_chemotherapy_in_dogs_with_osteosarcoma

Eligibility: Dogs with osteosarcoma that have completed a standard course of chemotherapy after limb amputation. Dogs
with a life expectancy of less than 1 month or who have lower urinary tract disease are ineligible.

Summary: Osteosarcoma is the most common primary bone tumor in dogs. Despite aggressive treatment with surgery and
chemotherapy, most dogs die of metastatic disease that is resistant to conventional chemotherapy. Metronomic
chemotherapy entails very small doses of chemotherapy that are given daily or every other day and help to deter the growth
of new blood vessels needed to nourish cancer as it grows. Side effects associated with metronomic chemotherapy tend to
be milder and less frequent than those seen with standard chemotherapy. The goal of this study is to evaluate for an
increased disease free interval in dogs treated with standard of care surgery and chemotherapy followed with maintenance
metronomic or low dose chemotherapy.

Requirement and incentive: This study is not funded; so pet owners are responsible for all costs associated with this
treatment.

Study: Evaluation of pamidronate in dogs with osteosarcoma (bone cancer)
Location: Tufts University Cummings School of Veterinary Medicine, North Grafton, MA
Phone: Kelly Reed, Oncology Liaison; (508) 887-4682
http://cgi.vet.tufts.edu/clinical_trials/projects/evaluation_of_pamidronate_in_the_treatment_of_canine_osteosarcoma

Eligibility: Dogs with osteosarcoma that have undergone surgery for removal of the affected limb and don't have any pre-
existing kidney disease.

Summary: Prior studies in the human and veterinary literature suggest that the use of a bisphosphate in the treatment of
canine osteosarcoma may be effective in extending overall survival. The goal of this study is to evaluate the tolerability and
efficacy of a bisphosphate, pamidronate, given in conjunction with standard of care chemotherapy for dogs with
appendicular osteosaroma post amputation.

Requirement and incentive: This study is not funded; pet owners are responsible for all costs associated with this treatment.

NEW JERSEY
Study: Funded Project for Dogs with Osteosarcoma
Location: Red Bank Veterinary Hospital
Phone: Clinical Trials Office at (732) 747-3636, ext. 1509
www.rbvh.net/trialdetails.php?Osteosarcoma-5

Eligibility: Eligible dogs are those who are scheduled for amputation due to the presence of appendicular osteosarcoma.
Eligibility includes dogs with suspected primary appendicular Osteosarcoma (based on physical exam or radiographs) or
confirmed diagnosis (based on previous cytology or histopathology of the affected limb (+/- metastasis). Dogs of all breed,
age, and sex are eligible. There is special interest in Greyhounds.

Dogs must not have received previous treatment for cancer, including chemotherapy, bisphosphonate therapy, prednisone
therapy, radiation therapy or immunotherapy. Previous or concurrent NSAID therapy is permitted. Concurrent acupuncture
is also permitted; though the acupuncture treatment must start > 2 weeks prior to sample collection.

Summary: Animal Clinical Investigation (ACI) requests to collect a biopsy following amputation. Following amputation, dogs
may receive treatment as chosen by the owner and veterinarian.

Financial Incentives: If a dog is eligible and enrolls in this study, for participation ACI will compensate pet owners $500
toward cost of amputation and $100 to clinic for cooperation.

NORTH CAROLINA
Study: Impact of Palladia™ on Canine Osteosarcoma
Location: North Carolina State University, Raleigh, NC
Contact: Study coordinator, Ms. Julie Osborne, RVT, at (919) 513-6812 or via email at julie_osborne@ncsu.edu
http://cvm.ncsu.edu/vth/clinical_services/onco/studies.html

Eligibility: Dogs with appendicular osteosarcoma with no radiographic evidence of pulmonary metastasis undergoing
amputation. 5 days following amputation dogs will begin Palladia™ and treatment will be continued until disease
progression. Clients will need to bring their pet in for evaluation according to the following schedule:

Summary:
•Initial consultation
•Amputation*
•Within 5 days after amputation: blood work, start Palladia™
•Week 1, 2 and 3 of Palladia*: blood work
•Monthly thereafter: blood work (every visit) and thoracic radiographs (every other visit)

*these tests may be performed with either the primary veterinarian or NCSU

Financial Incentives: The study will cover the costs of Palladia and blood work associated with drug monitoring. Clients will
be responsible for costs associated with initial evaluation, amputation, and every other month thoracic radiographs (approx.
$150/visit).

Study: The Impact of Metronomic Therapy following Amputation and Carboplatin Chemotherapy in
Canine Osteosarcoma
Location: North Carolina State University, Raleigh, NC
Contact: Study coordinator, Ms. Julie Osborne, RVT, at (919) 513-6812 or via email at julie_osborne@ncsu.edu
http://cvm.ncsu.edu/vth/clinical_services/onco/studies.html

Eligibility: Dogs with appendicular osteosarcoma with no radiographic evidence of pulmonary metastasis undergoing
amputation

Summary: Within 14 days following amputation, dogs will begin carboplatin chemotherapy (4 treatments at 3-week intervals)
followed by randomization to one of two metronomic therapy protocols.

Financial Incentives: The study will provide the chemotherapy drug carboplatin and the low-dose metronomic therapy
cocktail, as well as provide a financial incentive for follow-up monitoring. Clients will be responsible for costs associated with
initial evaluation, amputation, chemotherapy visit evaluation, and a portion of monthly follow-up visits.

PENNSYLVANIA
Study: L. monocytogenes vacine as therapy for dogs with bone cancer
Location: University of Pennsylvania Veterinary Hospital, Philadelphia, PA
Contact: 215-573-0302 or vcic@vet.upenn.edu
http://research.vet.upenn.edu/ClinicalStudies/CanineLymphoma/tabid/4518/articleType/ArticleView/articleId/26/New-Bone-
Cancer-Vaccine.aspx

Eligibility: Only those dogs with a confirmed diagnosis of osteosarcoma (by biopsy) and who have undergone limb
amputation and standard chemotherapy (4 doses of carboplatin) for the treatment of osteosarcoma will be eligible for
inclusion in the study. In addition, only those patients whose tumors express the target Her-2/neu will be eligible for inclusion
in this study.

Background: Osteosarcoma (bone cancer) is most commonly seen in large and giant breed dogs. It is an aggressive cancer
with a guarded prognosis, even when treated with amputation and chemotherapy. The purpose of this study is to determine
whether a recombinant L. moncytogenes vaccine can make the dog’s own immune system attack the tumor and prolong
survival in dogs with appendicular osteosarcoma.

Summary: The Veterinary Clinical Investigations Center is conducting a pilot phase I dose escalation study to determine the
dose of a L. monocytogenes expressing huHer-2/neu recombinant vaccine that can effectively stimulate tumor-specific
immunity and prolong survival in dogs with osteosarcoma. Only those dogs with a confirmed diagnosis of osteosarcoma (by
biopsy) and who have undergone limb amputation and standard chemotherapy (4 doses of carboplatin) for the treatment of
osteosarcoma will be eligible for inclusion in the study. In addition, only those patients whose tumors express the target Her-
2/neu will be eligible for inclusion in this study.

At enrollment (3 weeks following the last dose of carboplatin chemotherapy), all eligible dogs will receive basic clinical
laboratory tests including a complete blood count, chemistry screen and urinalysis and a baseline evaluation of cardiac
function by echocardiography and measurement of cardiac-specific Troponin I (cTnI) levels. Chest x-rays will be taken to
determine whether cancer has spread to the lungs (metastases). Only dogs with no evidence metastases will be eligible for
inclusion in the study. At the time of enrollment, a blood sample will be taken to assess immune function and baseline levels
of anti-tumor immunity.

All dogs will be vaccinated using a L. monocytogenes expressing huHer-2/neu recombinant vaccine, there is no placebo
group. The first vaccine will be given three weeks after the last dose of routine carboplatin chemotherapy. Patients will
receive a total of 3 vaccines given three weeks apart. Patients will stay in the hospital for 48 hours following vaccine
administration for observation.

Benefits:

Complete staging of disease at the time of enrollment (blood work, urinalysis, immune function assessment, chest x-
rays, cardiac evaluation)
Three Listeria monocytogenes vaccines
Hospitalization for observation
Blood work, urinalysis and cardiac evaluation every three weeks for a total of 9 weeks
Routine staging every 2 months following last vaccine administration (blood work, urinalysis, immune assessment,
chest x-rays, cardiac evaluation)

Costs: There is no cost to participate in this study. Initial diagnosis, amputation and standard of care chemotherapy
(carboplatin) and related charges are not covered by the study.