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DHEA in Synovial Sarcoma Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02683148
Recruitment Status : Terminated (The trial did not show any positive effects.)
First Posted : February 17, 2016
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE February 11, 2016
First Posted Date  ICMJE February 17, 2016
Last Update Posted Date September 9, 2019
Actual Study Start Date  ICMJE September 13, 2016
Actual Primary Completion Date September 9, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2016)
  • 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 shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diaters while on study
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
  • 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 shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diaters while on study
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2016)
  • 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 Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DHEA in Synovial Sarcoma Patients
Official Title  ICMJE 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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Synovial Sarcoma
  • Sarcoma, Synovial
Intervention  ICMJE
  • Drug: DHEA
    Other Name: Dehydroepiandrosterone
  • Other: FACT-67 validated survey
    • Baseline, Cycle 1 Day 15, and Day 1 of each cycle beginning with Cycle 2
    • 7 questions with answers ranging from 0=Not At All to 4 = Very Much.
Study Arms  ICMJE
  • Experimental: Arm 1: DHEA Dose Level 1
    -DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
    Interventions:
    • Drug: DHEA
    • Other: FACT-67 validated survey
  • Experimental: Arm 2: DHEA Dose Level 2
    -DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
    Interventions:
    • Drug: DHEA
    • Other: FACT-67 validated survey
  • Experimental: Arm 3: DHEA Dose Level 3
    -DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
    Interventions:
    • Drug: DHEA
    • Other: FACT-67 validated survey
  • Experimental: Arm 4: DHEA Phase II
    -DHEA is an oral supplement which will be administered on an outpatient basis at the prescribed dose daily on a 28-day cycle.
    Interventions:
    • Drug: DHEA
    • Other: FACT-67 validated survey
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 4, 2019)
11
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2016)
47
Actual Study Completion Date  ICMJE April 4, 2019
Actual Primary Completion Date September 9, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of histologically or cytologically confirmed metastatic or non-resectable synovial sarcoma.
  • Failed at least one line of chemotherapy. Neoadjuvant and adjuvant chemotherapy count as a prior line of therapy.
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
  • At least 16 years of age.
  • ECOG performance status ≤ 2
  • Normal bone marrow and organ function as defined below:

    • Leukocytes ≥ 3,000/mcL
    • Absolute neutrophil count ≥ 1,500/mcl
    • Platelets ≥ 50,000/mcl
    • Total bilirubin ≤ 1.5 x IULN
    • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
    • Creatinine ≤ IULN OR Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Patients using antiestrogens for oral birth control are ineligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • A history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  • Currently receiving any other investigational agents.
  • Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to DHEA or other agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
  • Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with DHEA. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  • Known mania-associated psychiatric disorder.
  • Known seizure disorder.
  • Using corticosteroids or estrogen-based oral birth control.
  • Using drugs known to lower or increase levels of DHEA.
  • Requires estrogen or testosterone.
  • Taking warfarin sodium. Patients on other blood thinners should be monitored for thrombocytopenia.
  • Taking a strong inhibitor or inducer of cytochrome P450. Intermediate inhibitors are allowed if deemed medically necessary.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02683148
Other Study ID Numbers  ICMJE 201603100
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Brian A Van Tine, M.D., Ph.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP