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DHEA in Synovial Sarcoma Patients

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ClinicalTrials.gov Identifier: NCT02683148
Recruitment Status : Recruiting
First Posted : February 17, 2016
Last Update Posted : September 7, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Synovial Sarcoma Sarcoma, Synovial Drug: DHEA Other: FACT-67 validated survey Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Clinical Trial of Dose-Escalating DHEA in Synovial Sarcoma Patients
Actual Study Start Date : September 13, 2016
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.

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.
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.

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.
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.

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.
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.




Primary Outcome Measures :
  1. 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%)

  2. 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


Secondary Outcome Measures :
  1. 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.

  2. 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.



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02683148


Contacts
Contact: Brian A Van Tine, M.D., Ph.D. 314-362-5737 bvantine@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Brian A Van Tine, M.D., Ph.D.    314-362-5737    bvantine@wustl.edu   
Principal Investigator: Brian A Van Tine, M.D, Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Brian A Van Tine, M.D., Ph.D. Washington University School of Medicine

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02683148     History of Changes
Other Study ID Numbers: 201603100
First Posted: February 17, 2016    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Synovial
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Dehydroepiandrosterone
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs