Clinical trials for dogs with cancer.

COLORADO
Study: COTC024: Defining PK (pharmacokinetics) and biological activity of systemic oncolytic VSV
within a dose-schedule optimization study
Locations: Colorado State University

Purpose of the study: To define optimal dose and schedule of administration for systemic VSV treatment in dogs with
cancer. VSV is a naturally oncolytic virus that has been engineered to possess potent anti-cancer properties with
enhanced safety.

Eligibility:

Dogs that weigh at least 20 kg (44lb)
Histological/cytological diagnosis of malignancy
Not hemangiosarcoma or mast cell tumor
Dog must be feeling well, with adequate routine blood work (blood count, chemistry panel, urinalysis)
Dogs must be up to date on all routine vaccinations
Must have a 2 week washout from chemotherapy, 7 day washout from corticosteroids, and a 6 week washout from
radiation therapy

Study Protocol:

Pre-study appointment to determine eligibility: Physical exam and history, bloodwork, chest x-rays, +/- abdominal
ultrasound
First day of study (Mondays): Pre-treatment physical exam, tumor measurements, blood samples, lymph node
aspirates, tumor biopsies
Second day of study (Tuesdays): Virus administration, monitoring and blood sampling
Dog must remain in the hospital Tuesday-Friday for in-hospital care, monitoring, and further tumor biopsies and
treatment (possible second dose of virus).
Once dismissed from the hospital there are weekly appointments until day 29 of the study.

Owner Responsibilities: Cost of diagnostics to determine eligibility (bloodwork, urinalysis, chest x-rays, +/- abdominal
ultrasound, histological/cytological confirmation of the diagnosis). To make and keep all appointments, according to clinical
trial protocol

Cost: Once enrolled, the study will pay for all costs associated with the study procedures and treatments. Study will also
cover cost of side effects attributable to the virus treatment or study procedures (up to $2000/dog/event). A $1000 credit
will be applied to the dog's account at the VTH, which can be applied toward further treatments

KANSAS
Study: Evaluation of locally-delivered nanotherapy cisplatin in combination with radiation therapy in
dogs with any malignant tumor.
Location: Kansas State University
Recruitment Open until 08/31/2018
For more information, please contact Misty Bear, Clinical Trials Coordinator, at (785)532-3046 or ClinicalTrials@vet.k-state.
edu

Eligibility:

Dogs with any cytologically- and/or histologically- confirmed, externally-measurable malignant tumor, not amenable
to surgical resection for whatever reason, that are good candidates for radiation therapy would be considered for
enrollment.
Dogs of any breed, age, gender and weighing a minimum of 10.0kg (22lbs), with a satisfactory health score.
Complete staging/re-staging would be required prior to study enrollment, including blood work (CBC and chemistry),
urinalysis, thoracic radiographs or computed tomography of the thorax, and/or abdominal ultrasound or computed
tomography of the abdomen.
Prior surgery, chemotherapy (excluding a platinum agent), corticosteroids, NSAIDs, and/or radiation therapy is
allowable if reoccurrence or progression is documented at the time of study enrollment with minimum washout
periods of one month for radiation therapy, three weeks for chemotherapy, and 72 hours for NSAIDs and/or
corticosteroid therapy. Concurrent chemotherapy, corticosteroids and/or radiation therapy are not allowable.

Summary: This trial evaluates the administration and clinical response to a new conjugate of cisplatin chemotherapy,
administered in combination with palliative radiation therapy, in dogs with any naturally-occurring, externally-measurable,
malignant tumor, which is not amenable to surgical resection for whatever reason.

Cisplatin is considered one of the most potent and broad spectrum chemotherapeutic agents; however, is associated with
significant side effects. This reformulation of cisplatin into a nanoparticle conjugate has shown promise as a safer, less
toxic and efficacious alternative.

Requirements: All enrolled dogs will receive the cisplatin conjugate subcutaneously to the primary tumor on study days 0,
7, 14, and 21, at incrementally increasing doses. Within 4 hours of cisplatin conjugate administration, enrolled dogs will
also concurrently receive one fraction of radiation therapy to the tumor site (for a total of 4 factions). Blood samples will be
collected immediately prior to each dose of chemotherapy, and also weekly for three weeks following the final dose. After
study day 42 (or sooner if your dog is removed from the study), the study will be completed and the oncology clinician will
discuss additional treatment options with you.

Cost: This study will cover the costs of recheck visits up to and including study day 42. This includes physical exam,
bloodwork, and urinalysis, as well as the costs of 4 doses of cisplatin conjugate and 4 fractions of radiation therapy. The
owner is responsible for the costs associated with staging prior to enrollment, including the initial oncology consultation,
chest x-rays, abdominal ultrasound, and computed tomography (CT) imaging.

NEW YORK
Study: Targeted Electrochemotherapy Cancer Treatment for local cancer control
Location: Veterinary Oncology Services, Middletown, NY.
Recruitment Open until 03/16/2019
For more information, please contact J Impellizeri, DVM, DACVIM at info@petcancerinformation.com, 845-205-2768

Eligibility: Diagnosis of malignancy.

Description: The electrochemotherapy (ECT) treatment consists of delivering, either systemically or locally, non-permeant
cytotoxic drugs (e.g. bleomycin) or low-permeant drugs (i.e. cisplatin) and applying electric pulses to the area to be treated
when the concentration of the drug in the tumor is at its peak. With the delivery of the electric pulses, cells are subjected to
the electric field that causes the formation of nanoscale defects on the cell membrane which alter the permeability of the
membrane. At this stage and for some time after pulses are delivered, molecules of the cytotoxic agents can freely diffuse
into the cytoplasm and exert their cytotoxic effect. Multiple positioning of the electrodes, and subsequent pulse delivery,
can be performed during a session to be able to treat the whole lesion, provided that drug concentration is sufficient.
Treatment can be repeated over the course of weeks or months to achieve regression of large lesions. In a number of
clinical studies in people (phase II and phase III) investigators have concluded that electrochemotherapy of cutaneous or
subcutaneous metastasis or tumors with bleomycin and cisplatin have an objective response rate of more than 80%.

Reduction of tumor size has been achieved with electrochemotherapy faster and more efficiently than in standard
chemotherapy for both cutaneous and subcutaneous tumors. Patients with skin metastasis from melanoma, Kaposi
sarcoma, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma or breast cancer have been successfully
treated. First clinical results of electrochemotherapy of internal tumors (e.g. liver metastases) and bone lesions are also
promising and encouraging. Electrochemotherapy employs lower dosages of chemotherapeutic drugs than standard
chemotherapy protocols. In the clinical use of electrochemotherapy limited side effects related to bleomycin or cisplatin use
are recorded. Provided that appropriate anesthesia is used for alleviation of the symptoms associated with application of
electric pulses, the control of the pain level during the electrochemotherapy is good and acceptable for the patients.
Beside pain which is limited to the treated tumor and surrounding tissue, muscle contraction during electric pulse delivery is
the only discomfort for human patients associated with electrochemotherapy. There is also induction of a vascular lock by
the type of pulses used in electrochemotherapy: for a few minutes blood flow is interrupted in the treated volume in the
normal tissues. Its duration is too short to induce deleterious effects due to ischemia. In tumors however, vascular lock is of
a longer duration and can contribute to the effectiveness of the electrochemotherapy. A good indicator that
electrochemotherapy is not a stressful or painful procedure is that the majority of the people interviewed during a clinical
study aimed at defining the European Standard Operating Procedure of Electrochemotherapy (ESOPE) would be willing to
accept the treatment another time if it would be necessary.

Currently, Electrochemotherapy in animals is under anesthesia and with a variety of probes available to us, many tumor
types and locations (including internal cancers) are candidates for this therapy. Some veterinary publications highlighting
tumors treated with this technique. Electrochemotherapy, in veterinary oncology (dogs, cats, exotics and horses), has been
dominated by centers in Brazil, France, Italy, Ireland, Slovenia and UK, until now where we have it here in the U.S. It is used
for a wide variety of tumors including: Fibrosarcoma in the mouth, eyelid, foot pad, skin or distal limb, Feline vaccine-
associated fibrosarcoma before and after surgery, Melanoma in the mouth, eyelid or foot pad, Squamous cell carcinoma in
mouth, eyelid, ear, nasal planum or foot pad, Incompletely resected soft tissue sarcomas where aggressive surgical
treatment would necessitate amputation, Localized cutaneous lymphoma in dogs or cats, Local control of mast cell tumors,
Perianal & rectal tumors, prostate, pancreas, Hepatocellular carcinomas/adenomas after resection, Perianal tumors,
Operation site margins where there is significant risk of remaining tumor tissue, Sarcoids, sarcoma and squamous cell
carcinomas in horses, Superficial tumors on exotics (small mammals, birds & zoo animals).

If you are interested in this clinical trial, please go to www.petcancerinformation.com and have your veterinarian fill out the
referral form. Please fax or email this along with pertinent lab results. If your pet is a candidate, the site will contact you
about the next step.

Study: Evaluating a DNA plasmid immunotherapy (B7-1) to stimulate anti-tumor immunity and prolong
survival times in dogs, cats and horses with various cancers
Location: Veterinary Oncology Services, Middletown, NY.
Recruitment End Date: 01/01/2020
For more information, please contact J Impellizeri, DVM, DACVIM at info@petcancerinformation.com, 845-205-2768
www.petcancerinformation.com

Eligibility: Diagnosis of malignancy, travel to other locations across the U.S. is possible for an additional cost.

Description: Veterinary Oncology Services (VOS; www.petcancerinformation.com) continues to provide various cancer
vaccine with published efficacy in canine and animal models. This treatment is from their partnership with the Cork Cancer
Center in Cork, Ireland and involves generating a strong patient immune response against the tumor as it forces the tumor
to act as its own antigen presenting cell (APC) and 'turn on' to be recognized by the patient's immune system, effectively
shutting down the tumor. This is a non-placebo study and will typically require a single treatment to the patient. This
immune pathway follows the PD-L1 pathway showing such promise against human cancers. Go to http://www.researchpd-l1.
com/ for a great link to this research on the human side. Cancer can evade immune destruction by upregulating the
inhibitory ligand PD-L1 on tumor cells and tumor infiltrating immune cells, such as macrophages and dendritic cells. PD-L1
binds to B7-1 and PD1 on cytotoxic T cells, disabling the anticancer immune response.

BACKGROUND: The B7-1 (CD80) costimulatory molecule is usually expressed on the membrane of professional APCs,
such as dendritic cells or B cells, initially binding to CD28 on CD4+ (helper) T cells, and subsequently acting as a second
signal following antigen-TCR engagement. Tumor cells usually lack expression of CD80 and without this costimulatory
signal, T cells may become clonally anergic when the TCR signal is delivered. B7-1- transduced tumor cells are expected
to present both the antigen (TCR receptor) and the costimulatory (CD28- mediated) signals to CD8+ cytotoxic T
lymphocytes (CTLs) simultaneously, leading to efficient activation of CTLs without requiring the assistance of CD4+ helper
T cells. Genetic Vaccines are not new but newer methods to improve greater DNA uptake has led to in-vivo electroporation
(DNA-EP) or electrogenetherapy (EGT)). Inoculating plasmid DNA encoding for a protein antigen by means of a simple
intramuscular or intradermal injection currently offers a vaccine approach that is easily performed, safe for host and
relatively inexpensive. However, target cells lack the co-stimulatory molecules needed as part of the CTL activation
process, therefore DNA vaccination is in general poorly efficient unless an inflammatory stimulus is applied in parallel or in
this case if a co-stimulatory molecule is inserted (B7.1). This mode of administration through DNA-EP will allow
maintenance of anti-tumor immunity. This approach uses brief electrical pulses that create transient pore in the cell
membrane, thus allowing large molecules such as DNA or RNA to enter the cell cytoplasm. Immediately following cessation
of the electrical field, these pores seal and the molecules are trapped in the cytoplasm without causing cell death. The
vaccine/immunotherapy has published data: Non-viral immune electrogene therapy induces potent antitumour responses
and has a curative effect in murine colon adenocarcinoma and melanoma cancer models. The clinical application of the
treatment involves access to the tumor either via surgery (lung metastasis with thoracoscopy, abdominal exploratory of
minimally invasive laparoscopy, open surgery, or accessible surgery such as a exteriorized tumor on the skin). Cancer with
evidence of spread can be accessed at only one site which affects the entire body no matter where the cancer has spread.
Once accessed, we will provide standard electrochemotherapy (ECT) to one part of the tumor and immunotherapy with
electrogenetransfer (EGT) to another site on the exposed tumor with the B7.1--essentially provide a local tumor response
(ECT) combined with systemic immune approach (plasmid and EGT). A single treatment is all that is needed. No placebos
are involved. The study is unfunded. The immunotherapy is unlicensed. There are no guarantees and some patients may
not benefit.

If you are interested in this clinical trial, please go to www.petcancerinformation.com and have your veterinarian fill out the
referral form. Please fax or email this along with pertinent lab results. If your pet is a candidate, the site will contact you
about the next step.

REFERENCES:
- Non-viral immune electrogene therapy induces potent antitumour responses and has a curative effect in murine colon
adenocarcinoma and melanoma cancer models. Forde PF, Hall LJ, de Kruijf M, Bourke MG, Doddy T, Sadadcharam M,
Soden DM. Gene Ther. 2015 Jan;22(1):29-39.
- Enhancement of electroporation facilitated immunogene therapy via T-reg depletion. Forde PF, Sadadcharam M, Hall LJ,
O' Donovan TR, de Kruijf M, Byrne WL, O' Sullivan GC, Soden DM. Cancer Gene Ther. 2014 Aug;21(8):349-54.
- Effective immunotherapy of weakly immunogenic solid tumors using a combined immunogene therapy and regulatory T-
cell inactivation. Whelan MC, Casey G, MacConmara M, Lederer JA, Collins JK, Tangney M, O'Sullivan GC. Soden DM
Cancer Gene Ther. 2010 Jul;17(7):501-11.
- Local gene therapy of solid tumors with GM-CSF and B7-1 eradicates both treated and distal tumors. Collins CG,
Tangney M, Larkin JO, Casey G, Whelan MC, Cashman J, Murphy J, Vejda S, McKenna S, Kiely B, Collins JK, Barrett J,
Aarons S, O'Sullivan GC. Soden DM. Cancer Gene Ther. 2006 Dec;13(12): 1061-71.

Study: Evaluating a targeted Telomerase vaccine in combination with a HER2 vaccine to stimulate anti-
tumor immunity and prolong survival times in dogs and cats with osteosarcoma, mammary cancer and
transitional cell carcinoma
Location: Veterinary Oncology Services, Middletown, NY.
Recruitment End Date: 01/01/2020
For more information, please contact J Impellizeri, DVM, DACVIM at info@petcancerinformation.com, 845-205-2768
www.petcancerinformation.com

Eligibility: Diagnosis of malignancy, travel to other locations across the U.S. is possible for an additional cost.

Description: Veterinary Oncology Services (VOS; www.petcancerinformation.com) continues to provide this cancer vaccine
with published efficacy against canine lymphoma. VOS continues to investigate the benefit of treating other naturally
occurring dog and cat cancers with this genetic DNA telomerase cancer vaccine followed by DNA vaccination using a
plasmid encoding telomerase. The non-funded study will enroll dogs and cats with various cancers including
lymphosarcoma, hemangiosarcoma, carcinoma, melanoma, transitional cell carcinoma and others in a non-placebo study.

BACKGROUND: The use of a telomerase vaccine targets a protein whose enhanced expression is a common characteristic
present in 85-95% of both human and animal cancer cells. Telomerase is not expressed in most differentiated cells making
it an ideal target for cancer therapeutics. Upregulated telomerase allows for limitless replication thus tricking the cell to
avoid apoptosis (programmed cell death) in lieu of continued replication of a malignant oncogene. The vaccine may be
used in naive (non-treated) patients but we feel the effect will be limited to absent. Our goal specifically in canine
lymphosarcoma patients is to obtain clinical and preferably molecular remission with standard of care chemotherapy and
use the vaccine concurrently. In other cancers, concurrent use of vaccine with standard of care therapies is encouraged
and may be coordinated with your treating oncologist.

Therapeutic vaccines are an important progressive approach which, when combined with other therapies, can improve
long-term control of cancer. A variety of immunization technologies are being explored. Among them, genetic (DNA-based)
vaccines are emerging as promising methodologies to induce immune responses against a wide variety of tumor antigens,
including telomerase. Recent findings show that combinations of different modalities of immunization (heterologous
prime/boost) are able to induce superior immune reactions as compared to single-modality vaccines. Our investigational
vaccine harnesses this type of innovative combination. Genetic Vaccines are not new but newer methods to improve
greater DNA uptake has led to in-vivo electroporation (DNA-EP) or electrogenetherapy (EGT)). Inoculating plasmid DNA
encoding for a protein antigen by means of a simple intramuscular or intradermal injection currently offers a vaccine
approach that is easily performed, safe for host and relatively inexpensive. However, target cells lack the co-stimulatory
molecules needed as part of the CTL activation process, therefore DNA vaccination is in general poorly efficient unless an
inflammatory stimulus is applied in parallel. This mode of administration through DNA-EP will allow maintenance of anti-
tumor immunity.

This approach uses brief electrical pulses that create transient pores in the cell membrane, thus allowing large molecules
such as DNA or RNA to enter the cell cytoplasm. Immediately following cessation of the electrical field, these pores seal
and the molecules are trapped in the cytoplasm without causing cell death. The vaccine has published data in Europe (see
below). Results show that Ad6/DNA-EP-based cancer vaccine against dTERT overcomes host immune tolerance, should
be combined with chemotherapy, induces long-lasting immune responses, and significantly prolongs the survival of ML
canine patients. These data support further evaluation of this approach in human clinical trials. and published data here in
the U.S. (see below) Client-owned pet dogs represent exceptional translational models for advancement of cancer
research because they reflect the complex heterogeneity observed in human cancer.

We have recently shown that a genetic vaccine targeting dog telomerase reverse transcriptase (dTERT) and based on
adenovirus DNA electro-gene-transfer (Ad/DNA-EGT) technology can induce strong cell-mediated immune responses
against this tumor antigen and increase overall survival of dogs affected by B-cell lymphosarcoma (LSA) in comparison
with historical controls when combined with a cyclophosphamide, vincristine, and prednisone (COP) chemotherapy
regimen. Here, we have conducted a double-arm clinical trial with an extended number of LSA patients, measured the
antigen-specific immune response, and evaluated potential toxic effects of the immunotherapy along with a follow-up of
patients survival for 3.5 years. The immune response was measured by enzyme-linked immunospot assay. The expression
of dTERT was quantified by quantitative polymerase chain reaction.

Changes in hematological parameters, local/systemic toxicity or organic dysfunction and fever were monitored over time
during the treatment. dTERT-specific cell-mediated immune responses were induced in almost all treated animals. No
adverse effects were observed in any dog patient that underwent treatment. The overall survival time of vaccine/COP-
treated dogs was significantly increased over the COP-only cohort (>76.1 vs. 29.3 weeks, respectively, p<0.0001). There
was a significant association between dTERT expression levels in LSA cells and overall survival among vaccinated
patients. In conclusion, Ad/DNA-EGT-based cancer vaccine against dTERT in combination with COP chemotherapy is safe
and significantly prolongs the survival of LSA canine patients. These data confirm the therapeutic efficacy of dTERT
vaccine and support the evaluation of this approach for other cancer types as well as the translation of this approach to
human clinical trials.

PROCEDURE: The vaccine is a series of 5 treatments (2 adenovirus/dTert) followed by 3 DNA/plasmid administered via
electrogenetherapy (EGT). Each is administered every 2 weeks and there is an option for continued monthly boosters for
those patients maintaining remission. The first two (2) adenovirus vaccines (prime) are administered via simple intra-
muscular injection. The last three (3) of the series (boosters) are administered under a short anesthesia via EGT. EGT is
under a short anesthesia and is a technically exciting mechanism of cancer vaccine delivery limited by a special generator
that delivers the electrical impulse to open the cell membrane. Clinical usage of the vaccine thus far has not shown any
limiting side effects nor toxicities. No placebos are involved. The study is unfunded. There are no guarantees and some
patients may not respond.

REFERENCES:
Electro-gene-transfer as a new tool for cancer immunotherapy in animals.Impellizeri JA, Ciliberto G, Aurisicchio L.Vet Comp
Oncol. 2014 Dec;12(4):310-8. doi: 10.1111/vco.12006. Epub 2012 Oct 25. Review.
A vaccine targeting telomerase enhances survival of dogs affected by B-cell lymphoma.Peruzzi D, Gavazza A, Mesiti G,
Lubas G, Scarselli E, Conforti A, Bendtsen C, Ciliberto G, La Monica N, Aurisicchio L. Mol Ther 2010 Aug;18(8):1559-67.
doi: 10.1038/mt.2010.104. Epub 2010 Jun 8.
Telomerase and HER-2/neu as targets of genetic cancer vaccines in dogs.Peruzzi D, Mesiti G, Ciliberto G, La Monica N,
Aurisicchio L.Vaccine. 2010 Feb 3;28(5):1201-8. doi: 10.1016/j.vaccine.2009.11.031. Epub 2009 Nov 26.
Safety and efficacy of a genetic vaccine targeting telomerase plus chemotherapy for the therapy of canine B-cell
lymphoma. Gavazza A1, Lubas G, Fridman A, Peruzzi D, Impellizeri JA, Luberto L, Marra E, Roscilli G, Ciliberto G,
Aurisicchio L. Hum Gene Ther. 2013 Aug;24(8):728-38.

If you are interested in this clinical trial, please go to www.petcancerinformation.com and have your veterinarian fill out the
referral form. Please fax or email this along with pertinent lab results. If your pet is a candidate, the site will contact you
about the next step.

Study: Combination of electrochemotherapy and gene therapy with canine IL-12
Location: Veterinary Oncology Services, Middletown, NY.
Recruitment End Date: 04/10/2019
For more information, please contact J Impellizeri, DVM, DACVIM at info@petcancerinformation.com, 845-205-2768
www.petcancerinformation.com

Inclusion criteria: A cytologic or histopathologic confirming diagnosis of skin/oral tumors, other tumors by permission.
Patients with > 3 months expected survival. The owner must understand the procedures and possible side effects. Signed
form of agreement for the participation in the study.

Exclusion criteria: Animals with severe renal dysfunction and heart disease. Animals with other diseases, which can cause
the life expectancy < 3 months. Animals with current chemotherapy or those which have been on chemotherapy in the last
2 weeks . Animals with immunosuppressive treatment and those which have been on immunosuppressive drugs in the last
14 days. Pregnancy and lactation

Description: Electrochemotherapy (ECT) is a standard treatment in veterinary oncology. It has been routinely used in dogs
for treating mast cell tumors, in cats for SCC and in horses for sarcoid tumors. ECT is a local ablative technique which has
a good local antitumor control in dogs (up to 70%) and in cats (up to 80%) and in horses up to 100% but limited impact on
distant tumors and metastasis. Therefore, there is a need for a combination therapy which could provide local control with
a systemic effect. Interleukin 12 is a potent immune stimulator that works by increasing IFN gamma which has an antitumor
effect through the activation of cytotoxic cells such as natural killer cells and cytotoxic T lymphocytes. IL-12 also
upregulates antigen presenting cells making the tumor cells recognizable to the effector cells. Several clinical studies have
already been performed treating different canine tumors by electro-genetransfer with a plasmid encoding IL-12. Results
showed increased systemic IL-12 and IFN gamma with an effect on distant metastasis 4–6. All of the described studies
used feline or human IL-12. We constructed a plasmid encoding canine IL-12 which is less likely to evoke an immune
reaction due to the non-homologous protein. Also the plasmids used had ampicillin resistance gene which is not allowed
by the FDA. Our plasmid has kanamycin resistance gene which is allowed by FDA due to the less common use in the clinic.
Procedure: The treatment consists of electrochemotherapy with bleomycin (intravenously or intratumorally) or cisplatin
(intratumorally) and gene electrotransfer of IL-12 (peritumorally). The treatment will be performed in patients under general
anesthesia. Depending on the tumor volume and the response the treatments will be repeated every 4 weeks. The therapy
consisted of two phases.

Procedure: In the first phase, electrochemotherapy will be performed using direct intratumoural application of cisplatin or
intratumoral or intravenous application of bleomycin. One to two minutes after intratumoural injection of the drug, eight
electric pulses will be delivered (each of 100 μs duration and amplitude to electric distance ratio of 1300V/cm and
frequency of repetition 5 kHz with electric pulses generator Cliniporator™ (IGEAs.r.l.,Carpi,Italy),using two parallel stainless
steel plate electrodes with 6 mm distance between them or four needle row electrodes with 4mm distance depending on the
size of the tumor. In the case of intravenously injected bleomycin, electric pulses, using the same parameters, will be
applied 8-10min later. Immediately after the completion of the first phase of the therapy, the second phase of therapeutic
procedure, IL-12 gene electro-genetransfer will be applied. The IL-12 plasmid will be injected intradermally in equidistant
locations around tumor nodule on two locations at the dose of 2 mg per patient. Immediately following injection of plasmid,
electric pulses will be delivered using different electrical parameters.

Potential Medical Benefits: Extended survival.

Potential Medical Risks: Anesthesia risks, local irritation.

References:
1. Pavlin, D. et al. Electrogene therapy with interleukin-12 in canine mast cell tumors. Radiol Oncol 45, 31–39 (2011).
2.Tozon, N., Pavlin, D., Sersa, G., Dolinsek, T. & Cemazar, M. Electrochemotherapy with intravenous bleomycin injection:
an observational study in superficial squamous cell carcinoma in cats. J. Feline Med. Surg. 16, 291–299 (2014).
3.Tamzali, Y. et al. Successful treatment of equine sarcoids with cisplatin electrochemotherapy: a retrospective study of 48
cases. Equine Vet J 44, 214–220 (2012).
4.Reed, S. D. et al. Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous
neoplasms in dogs. Cancer Gene Ther. 17, 457–64 (2010).
5.Cutrera, J., Torrero, M., Shiomitsu, K., Mauldin, N. & Li, S. Intratumoral bleomycin and IL-12 electrochemogenetherapy
for treating head and neck tumors in dogs. Methods Mol Biol 423, 319–325 (2008).
6.Cemazar, M. et al. Efficacy and safety of electrochemotherapy combined with peritumoral IL-12 gene electrotransfer of
canine mast cell tumours. Vet. Comp. Oncol. (2016). doi:10.1111/vco.12208

NORTH CAROLINA
Study: Open-label, phase-2 trial of Immunolight therapy for dogs with solid tumors
Location: North Carolina State University
Recruitment Open until 12/31/2018
For more information, please contact Corey Moore at 919-513-6453 or Carrie Emke at 919-515-8380 or
cvmclinicalstudies@ncsu.edu

Eligibility: Dogs with newly diagnosed oral melanoma or other solid tumors of the skin, toes, mouth, perineum. Internal
tumors are not eligible. Dogs may not receive other treatments for their tumor during the study.

Summary: The objective of this study is to evaluate the clinical and immunologic activity of Immunolight Therapy (IT) in
dogs with spontaneously-occurring solid tumors. The effect of IT on locally treated solid tumors will be measured via tumor
size reduction (Response Evaluation Criteria in Solid Tumors; RECIST). The effect of IT on pulmonary metastatic lesion will
be assessed via serial thoracic radiography. Changes in local, regional, and systemic immune activity will be measured via
flow cytometry of tumor, regional lymph node and distant lymph node samples, for lymphoid and myeloid markers, as well
as PD-1 expression. The effect of localized IT treatment of 2 lymphomatous lymph nodes on systemic disease burden will
be measured through a combination of lymph node size reduction (Response Evaluation Criteria in Solid Tumors;
RECIST), radiographic assessment of thoracic lesions, and cytologic assessment of previously affected nodes. Safety will
also be assessed; all clinical and biochemical toxicities will be graded according to the Veterinary Comparative Oncology
Group Common Terminology criteria for Adverse Events (VCOG-CTCAE) v1.1 (Veterinary Comparative Oncology, 2011).

Potential Medical Benefits: Potential reduction of tumor

Potential Medical Risks: Adverse events from study treatment

Cost: Fully funded including initial screening.