Ongoing Trials

COTC006: Evaluation Cryobiopsy Instrumentation And Cellsave Blood Collections In Dogs With Lymphoma.

Sponsor: National Cancer Institute-Division of Cancer Treatment and Diagnosis

Purpose: The development of novel and targeted cancer drugs has required innovative clinical trial designs that seek to define drug (pharmacokinetic) and host (pharmacodynamic) relationships early in the development process. For most new cancer agents it will be helpful if these pharmacodynamic endpoints are measured in tumor tissue. Many targets for cancer agents are influenced by variables including body temperature, pH, vascular supply, and enzyme activity following removal of tissues from the patient. Accordingly, novel tissue collection procedures and instruments are needed to ensure that pharmacodynamic endpoint assessments are not altered from their actual in vivo "state" during the collection process. This study aims to evaluate a novel biopsy instrument and compare it to standard biopsy techniques (Tru-cut, resection) and assess a novel blood collection method to identify circulating tumor cells.

Participating Sites:
University of Tennessee
University of Florida

Study Numbers:10-15 dogs anticipated

Eligibility Requirements:

• Diagnosis of nodal lymphoma via standard assessments i.e. cytology (histology may be confirmed following biopsy if needed)
• Measurable disease, naive (> 3 cm diameter) that is amenable to incisional biopsies of two distinct lymph nodes
• Informed owner consent for planned open surgical biopsy and lymph node resection
• Favorable performance status
• No previous treatment with chemotherapy or steroids
• No significant co-morbid illness, which includes but is not limited to renal or hepatic failure, history of congestive heart failure or clinical coagulopathy
• creatinine > 3.0
• bilirubin > 2.0 or elevated bile acids
• HCT < 25%, platelets < 50,000

COTC008: Evaluation of the mTOR inhibitor Rapamycin in Dogs with Metastatic Osteosarcoma.

Sponsor: Morris Animal Foundation and The Center for Cancer Research, NCI. Scientific endorsement from the Children's Oncology Group and the Sarcoma Alliance for Research through Cooperation (SARC).

Purpose: Signaling through the mTOR pathway has been recently shown to contribute to the growth, progression and chemo resistance of several cancers. Accordingly, agents that act against this pathway, namely Rapamycin and its analogs (Rapalogs), have been developed as potentially valuable therapeutics for cancer, with a particular emphasis on sarcomas and osteosarcoma. However the use of mTOR inhibitors requires optimization of dose and regimen. This study seeks to define and compare three schedules for chronic delivery of Rapamycin using endpoints of tolerability, blood Rapamycin levels, modulation of mTOR targets in the blood and anti-tumor activity against pulmonary metastatic disease. Dogs will receive intramuscular injections at home on varying schedules (sometimes daily) and return weekly to their COTC site for evaluation and serial blood collections. Tumor burden will be assessed monthly.

Participating Sites:
University of Tennessee
Colorado State University
University of Missouri
University of Pennsylvania
University of Wisconsin
Ohio State University
University of Illinios
Tufts University
University of California-Davis
Cornell University
University of Florida
University of Georgia
North Carolina State University
Purdue University

Study Numbers: 24-30 dogs anticipated (8 per schedule arm)

Eligibility Requirements:

• Radiographically measurable osteosarcoma pulmonary metastases (may be presumed based on clinical history)
• Pulmonary metastatic burden < 15 metastatic lesions; no lesion greater than 5 cm diameter. Concurrent organ metastatic sites are permissible.
• Rapamycin as the sole therapy (NSAIDs allowed if on for 30 days)
• Favorable performance status and life expectancy of at least 60 days
• Informed owner consent
• No significant co-morbid illness, which includes but is not limited to renal or hepatic failure, history of congestive heart failure or clinical coagulopathy
• creatinine > 3.0
• bilirubin > 2.0 or elevated bile acids
• HCT < 25%, platelets < 50,000

Closed Trials

COTC001: Evaluation of RGD Targeted Delivery of Phage Expressing TNF-alpha to Tumor Bearing Dogs.

Sponsor: The National Cancer Institute

Purpose: This clinical trial sponsored by the National Cancer Institute (NCI) evaluates the safety and effectiveness of the phage-based delivery of an agent known as Tumor Necrosis Factor (TNF alpha). TNF alpha is known to kill cancer cells and the blood vessels that feed them. It is currently used in human cancer patients as an isolated infusion and efforts to find new ways to deliver it safely have been underway for some time. The NCI has developed a special way to deliver TNF-alpha specifically to blood vessels around tumors using a molecular approach based on a viral-like carrier (phage). Results of this trial in dogs will be used to inform the design and implentation of planned clinical trails in human cancer patients.

Participating Sites:
Colorado State University
University of Missouri
University of Pennsylvania
University of Tennessee
University of Wisconsin

Study Numbers: 15-20 dogs will be enrolled in each study

Eligibility Requirements:

• Hisotogically confirmed, Measurable disease (<2cm), can be primary and/or metastatic
• Favorable performance status
• Naïve or recurrent disease
• Dogs must be more than 15kg
• Dogs cannot receive concurrent chemotherapy, radiation or angiogenesis for 4 weeks prior to study enrollment

COTC003 Study 1: Evaluation of the MTOR inhibitor Rapamycin in dogs with osteosarcoma

Sponsor: Morris Animal Foundation and The National Cancer Institute

Purpose: This clinical trial seeks to identify a safe, pharmacokinetically/ pharmacodynamically relevant dose of Rapamycin in tumor bearings dogs. Currently, Rapamycin is approved as an immunosuppressive agent used in the setting of organ and bone marrow transplant. Results of this trial will directly inform the development efforts of Rapamycin analogues currently underway by providing the groundwork for follow-up studies that will assess optional Rapamycin dose and schedule.

Participating Sites:
Colorado State University
The Ohio State University
University of Illinois
University of Wisconsin

Study Numbers: 20-25 dogs will be enrolled

Eligibility Requirements:

• Hitologically confirmed, osteosarcoma
• Favorable performance status
• Measurable disease that is amenable to serial biopsy
• No concurrent chemotherapy or radiation therapy for 2 weeks prior to study enrollment

Sponsor: Pharmaceutical Company

Purpose: A pre-clinical trial of immunocytokine in tumor bearing dogs is intended to define acute and chronic toxicities and activity of this immunotherapeutic agent in a spontaneous tumor model. The trial is divided into two steps: (1) Dose escalation & tolerability study --- in which we expect to gain insight into the optimal dose, and early indication of any anti-tumor activity and (2) Efficacy study with the best-chosen dose.

Participating Sites:
The Ohio State University
Cornell University
University of California at Davis
Tufts University
University of Tennessee

Study Numbers: 10-15 dogs will be enrolled to the first phase of this study.

Eligibility Requirements:

• histologically confirmed lymphoma melanoma or soft tissue sarcoma Favorable performance status
• both newly diagnosed dogs and those with recurrent disease are eligible
• Dogs cannot receive concurrent chemotherapy, radiation or angiogenesis for 3 weeks prior to study enrollment
• no current or of history of immune mediated disease (IMHA, ITP, SLE, etc)

Upcoming Trials

If you are interested in learning more about the eligibility requirements for any of the above studies, please contact the nearest participating University or Christina Mazcko at mazckoc@mail.nih.gov