Rapamycin in Dogs with Osteosarcoma

Rapamycin in Dogs with Osteosarcoma (OSA)

All potentially interested veterinarians and owners: PLEASE read the section NOTE TO OWNERS below, concerning the dosing of the drug.

Study Title

Evaluation of the mTOR Inhibitor Rapamycin in Dogs with Osteosarcoma. A multi-center national trial sponsored by the National Cancer Institute (NCI), Comparative Oncology Program, Comparative Oncology Trials Consortium, and the Morris Animal Foundation

Purpose of Study

The purpose of this study is to define a relevant dose and dosing schedule for Rapamycin in tumor bearing dogs. This is a dose escalation study (7 days) of Rapamycin in dogs with osteosarcoma (OSA) prior to resection/amputation. Serial pre- and post-treatment tumor biopsies will allow for assessment of tumor biomarkers, which will be correlated with serum biomarkers. After completion of this first phase, future studies will assess the anticancer activity of Rapamycin in dogs with metastatic OSA, alone and in combination with conventional chemotherapy.

Background Information

Rapamycin has been shown to inhibit mTOR activity, a pathway believed to be important for cancer progression and resistance to therapy. The NCI has shown that mTOR inhibition in human sarcoma cell lines has resulted in suppressed cancer cell proliferations and suppression of the metastatic cell types. Rapamycin is currently approved as an immunosuppressive agent for patients undergoing organ and bone marrow transplants. Its use in dogs has been limited due to their sensitivity to the drug; at higher doses it may cause gastrointestinal problems (potential adverse effects are listed below). However, therapeutic levels of Rapamcyin have been safely achieved in dogs following low-dose administration of the drug.

Study Timeline

  • An initial appointment to assess study eligibility, baseline imaging, possible cytology and blood work (cost of this visit is not covered by the study, estimated cost of $350-$500)
  • After enrollment, a pretreatment biopsy and serial whole blood samples (6 ml each) will be obtained at each of the following time points: 30 minutes, 1, 2, 6, 24, and 48 hours after the initial dose of Rapamycin. This visit will include an overnight stay at OSU for monitoring, with a return visit the next day
  • Subsequent doses will be given in one of the following ways:
  1. At home by the owner for 7 days, as an intramuscular injection.
  2. Return to OSU for daily injections
  3. Your dog will board at the hospital for one week and the injections will be given by the oncology staff.

All potentially interested veterinarians and owners: Please read the section NOTE TO OWNERS below, concerning the dosing of the drug.

 

  • Return to OSU for surgery on Day 8 for primary tumor resection/amputation. Blood collection will be done 24 and 48 hours after last dose
  • Return to OSU on Day 15 (1 week post surgery) for evaluation and blood collection
  • After this visit, then your dog can receive any adjuvant chemotherapy protocol. Your clinician will discuss the appropriate chemotherapy protocol for your dog.

Note to Owners

Daily administration of Rapamycin needs to be done by intramuscular (IM) injection. This type of injection will be demonstrated to you, but may be difficult for some owners. Administration will likely require two people, one to hold and one to administer the injection. Injection of the drug may sting. Your dog may also be sore at the site of injection, so the sites will need to be rotated daily. Due to the potential difficulty with IM injections, OSU is offering two other alternatives to owners instead of administering the Rapamycin at home. These are:

  1. Owners are able to bring their dogs into OSU daily for the IM injections. This would be a quick visit, which should not take more than 15 to 20 minutes.
  2. Owners will be able to board their dog at OSU for the week prior to surgery. This would allow for the Oncology staff to administer the drug daily. It would also decrease the risk of potential bone fracture due to the tumor, since your dog would be on cage rest.
  3. After the surgery and the Day 15 visit your dog will finish the study. Usually, chemotherapy protocols are started 2 weeks after surgery at the time of suture removal. Your clinician will discuss all the options available for adjuvant chemotherapy, which can be done at OSU and in some cases in conjunction with your local veterinarians.

Inclusion Criteria

  • Histologically confirmed osteosarcoma via biopsy
  • Dogs > 15 kg with measurable disease that is amenable to serial biopsy (incisional biopsy after amputation/resection)
  • Owner consent for surgical resection/amputation
  • Performance status of either normal activity or restricted activity (decreased from pre-disease status)
  • Newly diagnosed dogs and
  • Informed owner consent for the trial

Costs covered by study

All visits after the initial visit to establish eligibility will be covered by the study with the exception of surgery. The study will cover $800 to $1000 towards to the surgery but the remainder of the surgical cost would need to be covered by owners. The study will not cover any adjuvant chemotherapy following surgery.

If there are any adverse effects due to Rapamycin, the study will cover the cost of treatment; however, patients must come back to OSU to be treated. Potential effects must be reported with in the 15 day study period.

For more study specifics please contact Dr. William Kisseberth at clinicaltrials [at] cvm [dot] osu [dot] edu.

This study will start enrolling patients on April 2, 2007