Clinical Trials

Inclusion Criteria: 

• Signed consent of an Institutional Review Board-approved informed consent form and Health Insurance Portability and Accountability Act authorization for release of personal health information (if appropriate).
• Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• Disease status including all of the following:
  • Histological or cytological confirmation of LMS arising at any anatomic site;
  • Advanced (metastatic) or locally advanced unresectable disease;
  • Ineligible for other high-priority national or institutional study;
  • Measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 criteria.
• Age ≥ 18 years of age.
• Male or female.
• Eastern Cooperative Oncology Group performance status 0-1.
• Absolute neutrophil count ≥ 1,500/mm^3 without the use of growth factors in the past 7 days.
• Platelet count ≥ 100,000/mm^3 platelet transfusion in the past 5 days.
• Hemoglobin ≥ 9 g/dL (packed red blood cell transfusion is allowed).
• Bilirubin < upper limit of normal (ULN).
• Aspartate aminotransferase or alanine aminotransferase < 1.5 times ULN.
• Subjects with liver metastases may be enrolled.
• Subjects with well-controlled asthma (e.g., use of rescue medications < 2 times per week over the last 12 months) or chronic obstructive pulmonary disease (e.g., no exacerbations over the prior 3 months) may be enrolled.
• Creatinine < 1.5 times normal OR > 45 mL/min.
• Toxicity from prior therapies recovered to Grade ≤ 1 or subject’s baseline, except for alopecia. In addition, endocrinopathies associated with prior immunotherapy-based treatments that are well controlled on replacement medication are not exclusionary.
• Chemotherapy:
  • Up to and inclusive of 4 prior systemic cytotoxic oncology therapy regimens for metastatic, locally recurrent, or unresectable LMS, with the last dose of prior therapy administered no fewer than 30 days or 5 times the drug half-life prior to screening.
  • Note: prior treatment with non-cytotoxic therapy regimens (e.g., targeted therapies, hormonal therapies, or tyrosine kinase inhibitors) are not considered cytotoxic oncology therapies.
• At least 4 weeks since prior surgery and recovered in opinion of investigator.
• Capable of swallowing oral medication.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.
• Males and females of childbearing potential must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 90 days after treatment discontinuation.
  • Note: The definition of effective contraception will be based on the judgment of the principal investigator or designee.

Exclusion Criteria:

• Received any systemic anticancer therapy including investigational agents ≤ 3 weeks prior to initiation of study treatment. Additionally, subjects may not have received radiation ≤ 3 weeks prior to initiation of study treatment.
• Co-existing active infection or any co-existing medical condition likely to interfere with study procedures, including:
  • Significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, or evidence of ischemia on electrocardiogram (ECG), marked baseline prolongation of QT/QTc (corrected QT interval) interval; e.g., repeated demonstration of a QTc interval > 500 msec (Long QT Syndrome [congenital]).
• Known human immunodeficiency virus, hepatitis B virus, or hepatitis C virus positivity.
• History of solid organ transplantation.
• Known or suspected allergy or immediate or delayed hypersensitivity to unesbulin or dacarbazine or any agent given in this study.
• Bowel obstruction, malabsorption, or other contraindication to oral medication.
• Gastrointestinal disease or other condition that could affect absorption.
• Active peptic ulcer disease.
• Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis, or appendicitis.
• Any condition that impairs subject's ability to swallow oral medications.
• Serious non-healing wound, ulcer, or bone fractures.
• Major surgery, open biopsy, or significant traumatic injury, which has not recovered in the opinion of the investigator, within 28 days of baseline.
• Mucosal or internal bleeding.
• Concomitant strong CYP1A2 inhibitors (like selective serotonin reuptake inhibitor agents fluvoxamine and fluoxetine) should be avoided. CYP1A2 inhibitors may inhibit the conversion of DTIC to its active metabolite and may increase the exposure of unesbulin.
• Prior malignancies, other than LMS, that required treatment or have shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to initiation. Cancer treated with curative intent more than 5 years previously and without evidence of recurrence is not an exclusion.
• Known coagulopathy or bleeding diathesis. Subjects on anti-coagulation should be monitored closely and International Normalized Ratio within normal range.
• Prior or ongoing clinically significant illness, medical or psychiatric condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator’s opinion, could affect the safety of the subject, or alter the absorption, distribution, metabolism, or excretion of the study drugs, or could impair the assessment of study results.
• History of brain metastases or leptomeningeal disease at any time in subject’s history, including treated central nervous system disease which is clinically and radiographically stable.

Eligibility last updated 1/20/22. Questions regarding updates should be directed to the study team contact.