Clinical Trial: DHEA in Synovial Sarcoma Patients

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I/II Clinical Trial of Dose-Escalating DHEA in Synovial Sarcoma Patients

Brief Summary: DHEA is a natural allosteric inhibitor of glucose-6-phosphate dehydrogenase (G6PD). G6PD is a key regulatory enzyme for the survival of synovial sarcoma. The investigators postulate that they can inhibit the production of NADPH in synovial sarcoma and cause cell death by using a naturally occurring G6PD inhibitor.

Detailed Summary:
Sponsor: Washington University School of Medicine

Current Primary Outcome:

  • Maximum tolerated dose (MTD) of DHEA (Phase I only) [ Time Frame: Completion of cycle 1 for all phase I patients (estimated to be 2 years) ]
    • MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached.

    • Dose-limiting toxicities are defined as one of the following events occurring during the 1st cycle of treatment thought to be possibly, probably, or definitely related to treatment:

      • Grade 3 or greater liver function test abnormalities
      • Grade 3 or greater psychiatric disorder
      • Quality of life (QOL) alteration (change in score of 30%)
  • Progression-free rate (complete response + partial response + stable disease) (Phase II only) [ Time Frame: Up to 5 years ]
    • Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction inf short axis to <10mm, disappearance of all non-target lesions and normalization of tumor marker level.
    • Partial response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    • Stable disease (SD): neither sufficient shrinka

      Original Primary Outcome:

      • Maximum tolerated dose (MTD) of DHEA (Phase I only) [ Time Frame: Completion of cycle 1 for all phase I patients (estimated to be 2 years) ]
        • MTD is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached.

        • Dose-limiting toxicities are defined as one of the following events occurring during the 1st cycle of treatment thought to be possibly, probably, or definitely related to treatment:

          • Grade 3 or greater liver function test abnormalities
          • Grade 3 or greater psychiatric disorder
          • Quality of life (QOL) alteration (change in score of 30%)
      • Objective response rate (complete response + partial response + stable disease) (Phase II only) [ Time Frame: Up to 5 years ]
        • Complete response (CR): disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction inf short axis to <10mm, disappearance of all non-target lesions and normalization of tumor marker level.
        • Partial response (PR): at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
        • Stable disease (SD): neither sufficient shrin

          Current Secondary Outcome:

          • Rate of progression-free survival (PFS) (Phase II only) [ Time Frame: 3 months ]
            • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
            • Progressive disease (PD): aAppearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
          • Toxicity of DHEA as measured by grade and frequency of adverse events [ Time Frame: 30 days after completion of treatment (estimated to be 7 months) ]
            -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.


          Original Secondary Outcome: Same as current

          Information By: Washington University School of Medicine

          Dates:
          Date Received: February 11, 2016
          Date Started: September 13, 2016
          Date Completion: June 30, 2025
          Last Updated: April 11, 2017
          Last Verified: April 2017