Evaluation of STA-1474 dosed two consecutive days in dogs with spontaneous solid tumors

Purpose

The goal of this study is to determine if dosing STA-1474 on two consecutive days can be tolerated, and if so, identify the maximum tolerated dose; and determine the pharmacokinetic profiles of STA-1474 over the course of drug infusion.

 Background

This clinical trial is sponsored by Synta Pharmaceuticals Corporation and evaluates the ability of a new heat shock protein 90 (HSP90) inhibitor, STA-1474, to affect specific protein levels in mast cell tumors (MCTs). Heat shock protein 90 (HSP90) is a “chaperone” protein important in the maintenance of several cell proteins including Kit, Met, Akt, among others.  These proteins are needed to promote the survival and growth of cancer cells.  Several studies have shown that HSP90 activity is increased in many cancer cells and as such, inhibition of HSP90 would be expected to kill cancer cells.  A number of different clinical trials of HSP90 inhibitors in people, and now in dogs, have shown that inhibition of HSP90 can either stop tumors from growing, or shrink them partially.  At OSU, a study was performed in which 25 dogs with various tumors received STA-1474 to determine the maximum dose that could be given and to see if any specific tumor types responded to therapy.  The maximum dose used was 9.5 mg/kg and responses were seen in dogs with MCTs, osteosarcomas, and thyroid carcinoma.  Unlike standard chemotherapy agents, no effects of STA-1474 on red blood cells, white blood cells, platelets, liver, heart or kidney were found (i.e., the drug did not alter any standard bloodwork parameters).  The main side effects that did occur were diarrhea and lethargy (tiredness) and a few dogs did have some vomiting. These side effects were largely prevented using standard medications (anti-diarrhea and anti-nausea/anti-vomiting drugs) before the STA-1474 was administered.  In fact, in this previous study 7/25 dogs received 10 or more doses of STA-1474 with the longest dog on study receiving 38 treatments indicating that the STA-1474 is well-tolerated. 

Despite encouraging preliminary work, most of the HSP90 inhibitors have not been as effective as would have been predicted based on the laboratory studies and mouse studies.  The reason for this is not entirely known, but there is now evidence that these inhibitors may need to be given more frequently or over a longer duration than initially believed.  The purpose of this clinical trial is to determine the maximum tolerated dose of STA-1474 that can be given 2 days in a row to dogs to try to increase the effectiveness of HSP90 inhibition and therefore increase the ability to cause shrinkage/regression of existing tumors.

 Inclusion criteria

 To qualify for enrollment in this study, dogs must have:

  • Histologically or cytologically confirmed diagnosis of cancer;
  • Age > 1 year;
  • No evidence of other illness such as kidney, liver or heart disease;
  • At least 2 weeks apart from other investigational drug;
  • Must have an estimated life expectancy of at least 8 weeks
  • Prior radiation therapy or chemotherapy must have been completed at least 3 weeks prior to study entry.

 Study Design

Dogs with spontaneous tumors will undergo screening including complete blood count, chemistry panel, urinalysis and chest x-rays determine eligibility for the study. Your dog will receive standard medications prior to getting STA-1474 to prevent any diarrhea or vomiting.  Your dog will receive STA-1474 over 1 hr for two days in a row.  Blood samples will be taken through an IV catheter during and after STA-1474 administration to measure the levels of drug.  The number of blood samples drawn will be 9 per day representing a total of 20 ml (4 teaspoons) of blood.  For comparison, the amount of blood typically used for routine bloodwork tests is about 5 mls.  Your dog will be hospitalized for the two days of drug administration and will go home the day after the second infusion.  Your dog will return 7 days later for a final evaluation.  All costs associated with this study are covered by the study including management of any side effects that may occur.  Additionally, the study sponsor will provide $750 for continued treatment of your dog for cancer at the OSU VMC.  This can be applied to surgery to remove the tumor, or medical therapy/radiation therapy for the tumor.  

Client Compensation

All costs associated with this study are covered by the study including management of any side effects that may occur.  Additionally, clients will receive a $750 credit at the OSU VMC for continued treatment of their dogs cancer.  This can be applied to surgery to remove the tumor, or medical therapy/radiation therapy for the tumor.  

 Contact Information

 Nicole Stingle or Tamra Mathie at clinicaltrials [at] cvm [dot] osu [dot] edu