Prasterone in Treating Patients with Synovial Sarcoma That is Metastatic or Cannot Be Removed by Surgery
This phase I/II trial studies the side effects and the best dose of prasterone and to see how well it works in treating patients with synovial sarcoma that has spread from the primary site to other places in the body or cannot be removed by surgery. Prasterone may kill tumor cells by blocking an enzyme needed for cell growth.
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 computed tomography (CT) scan, as >= 20 mm by chest x-ray, or >= 10 mm with calipers by clinical exam
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcl
- Platelets >= 50,000/mcl
- Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x IULN
- Creatinine =< IULN OR creatinine clearance >= 60 mL/min/1.73 m^2 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 Institutional Review Board (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
- 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 human immunodeficiency virus (HIV)-positivity on combination antiretroviral therapy
- 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
Additional locations may be listed on ClinicalTrials.gov for NCT02683148.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of prasterone (dehydroepiandrosterone [DHEA]) in the treatment of synovial sarcoma. (Phase I)
II. To determine the progression free rate (complete response [CR] + partial response [PR] + stable disease [SD]) of patients with synovial sarcoma receiving the MTD of DHEA. (Phase II)
SECONDARY OBJECTIVES:
I. To determine the rate of progression-free survival (PFS) of patients with synovial sarcoma receiving DHEA in the Phase II portion of the trial.
II. To evaluate the toxicity of DHEA in the treatment of synovial sarcoma.
TERTIARY OBJECTIVES:
I. To evaluate malic enzyme 1 (ME1) expression of specimens collected from patients with synovial sarcoma being treated with DHEA.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive prasterone orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 5 years.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorBrian Andrew Van Tine
- Primary ID201603100
- Secondary IDsNCI-2016-00445
- ClinicalTrials.gov IDNCT02683148