Osteosarcoma Studies At Uw-Madison

[Victor]

I just read about 3 studies on osteosarcoma that are currently being conducted at UW-Madison. I hadn't heard of the first (administration of rapamycin after carboplatin), so that's interesting. Also, if you're in the Madison area and qualify for one of these studies, it could help offset the cost of surgery and/or treatment.

1. Evaluation of the Effect of Rapamycin Following Amputation and Carboplatin Chemotherapy on Disease-Free Survival in Dogs with Appendicular Osteosarcoma:

This clinical trial led by the National Cancer Institute (NCI) and sponsored by the Morris Animal Foundation seeks to evaluate in dogs with osteosarcoma the safety and effectiveness of Standard of Care therapy, with or without adjuvant rapamycin administration. Standard of Care is defined as definitive surgery, being amputation of the affected limb, followed by 4 doses of intravenous carboplatin chemotherapy given on a q21 day schedule. Carboplatin has been safely and effectively used to treat appendicular osteosarcoma in dogs for > 20 years, but the potential for unforeseen potentially life-threatening side effects from surgery, chemotherapy, and/or progressive cancer does exist. ALL dogs enrolled onto study will receive Standard of Care therapy; however, through a randomization process, some dogs entered into study will also receive additional therapy with oral rapamycin.

Rapamycin is a drug currently approved for immunosuppression during preparatory and maintenance regimens for organ and bone marrow transplant in human patients. Early work with rapamycin suggests that this agent might also have anti-cancer properties by inhibiting (reducing the effects of) an important pathway in cancer progression known as mTOR. Preclinical studies of rapamycin in mice, as well as recent data using analogous drugs in human patients (rapalogs), suggest that mTOR blockade might be effective in the treatment of several cancers. In a recently completed study of rapamycin in dogs with cancer, a dose and schedule for rapamycin administration have been defined which appears to be safe and tolerable by most dogs.

Within this study, dogs will undergo surgical amputation of the affected limb. Dogs will return to UW Veterinary Care every 3 weeks for 15 weeks for evaluation. On weeks 3, 6, 9 and 12, dogs will receive a dose of carboplatin. After 15 weeks of Standard of Care, based upon initial study randomization, dogs will either receive oral rapamycin on a 4 day on/3 day off schedule for 4 months or will not be treated with any additional medications and simply be monitored every 8 weeks.

Costs associated with this study (including carboplatin and rapamycin administration and study-related evaluations will be covered by the study. In addition, $1,000 will be provided towards the cost of surgical amputation.

2. Stereotactic Radiation Therapy for Pain Relief and Immune Modification in Dogs with Limb Osteosarcoma

Radiation therapy’s primary use for canine osteosarcoma has been with a palliative intent to alleviate pain. Stereotactic radiation therapy (SRT) is a highly accurate radiation delivery technique that potentially allows us to give a higher radiation dose per treatment in fewer treatment sessions. This study will deliver 3 radiation treatments over 3 days and assess pain relief with orthopedic exam, force platform analysis and client questionnaires. The primary aim of this study is to determine the effectiveness of stereotactic radiation therapy to alleviate pain. We hypothesize that most dogs will experience significant pain relief.

Large doses of radiation per treatment have also been proposed to stimulate an immune response against the cancer. To evaluate this, we aim to measure changes in proteins released from the tumor or its environment by collecting blood samples before, during and after the radiation therapy.

Dogs with a biopsy confirmed diagnosis of osteosarcoma of the limb may be eligible for this study. Dogs with a tumor-related fracture, spread of cancer to lymph nodes or lungs or previous radiation or chemotherapy are not eligible. A CT scan will be required for radiation planning and to determine study eligibility. Dogs will be evaluated at 1, 2, 4, 8 and 12 weeks after radiation therapy. Clients will receive financial compensation, which will cover the cost of radiation therapy and follow-up evaluations. Clients are responsible for the cost of diagnosis and tests to determine if their dog is eligible for this study.

3. Canine Osteosarcoma with Lung Metastasis

Osteosarcoma is the most common bone tumor encountered in dogs. A variety of therapies have been evaluated including surgery, radiation therapy, and “conventional” chemotherapeutic agents such as cisplatin, doxorubicin and carboplatin. While survival times are roughly tripled with the addition of chemotherapy following surgical removal of the tumor, approximately 80% of dogs will succumb to metastatic disease within 2 years. Conventional cytotoxic chemotherapy is rarely efficacious when measurable metastatic disease is present; the reported median survival times following detection of lung metastasis is approximately 60 days.

Palladia is FDA approved for treating canine mast cell tumors and has been found to have activity against a wide variety of other canine tumors including osteosarcoma. Preliminary studies have suggested that approximately 50% of dogs with measurable metastatic osteosarcoma will experience clinical benefit following Palladia treatment. The purpose of this study is to evaluate potential biomarkers of clinical benefit in dogs with metastatic osteosarcoma treated with Palladia.

Dogs with osteosarcoma that have developed lung metastasis may be eligible for this study. Palladia will be administered orally, by the owner, three times per week. Dogs will return to UW Veterinary Care for evaluation weekly for the first 28 days, again at week 8 and then every 8 weeks thereafter for as long as the dog is receiving Palladia. Palladia will be supplied at no cost and the chest X-ray performed at week 8 will be paid for by the study. All other costs for clinic visits and evaluations will be the owner’s responsibility.

 

 

For more information, see https://uwveterinarycare.wisc.edu/clinical-studies/oncology/

[Annette]

Unfortunately we may be taking part in the study for Rapamysin. We were in Madison most of the day today. Can someone tell me who designed that city? Once you get there, there is no easy way out

 

Has anyone ever had their pup participate in a study? If the pup does not tolerate the drug, etc in the study, can they be taken out of the study?

 

Thanks

[Victor]

We haven't, but that would be a good question to ask before signing up, in case there are unanticipated side effects. For example, when our angel Lana developed lung mets, we started her on Palladia, but she did not tolerate it well.

Edited November 15, 2015 by Victor

[Rickiesmom]

I've had a hound in a clinical trial and the terms explicitly stated the owner could withdraw the dog if needed. I am sure this will be something you can discuss with the trial administrators and also confirm when you receive the paperwork.