Clinical trial NCT02683148: DHEA in Synovial Sarcoma Patients
Official title: A Phase I/II Clinical Trial of Dose-Escalating DHEA in Synovial Sarcoma Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Synovial Sarcoma
Sarcoma, Synovial
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2016-02-17
Enrollment: 11
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) of DHEA (Phase I only)
timeFrame: Completion of cycle 1 for all phase I patients (estimated to be 2 years)
measure: Progression-free rate (complete response + partial response + stable disease) (Phase II only)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Rate of progression-free survival (PFS) (Phase II only)
timeFrame: 3 months
measure: Toxicity of DHEA as measured by grade and frequency of adverse events
timeFrame: 30 days after completion of treatment (estimated to be 7 months)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Brian A Van Tine, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: