Clinical Trials

Inclusion Criteria: 

• Signed consent of an Institutional Review Board (IRB)-approved informed consent form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) 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. 
• 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 RECIST v1.1 criteria. 
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 
• Hematopoietic:
  • Absolute neutrophil count (ANC) count greater than or equal to (≥) 1,500/cubic millimeters (mm^3);
  • Platelet count ≥ 100,000/mm^3;
  • Hemoglobin ≥ 9 grams per decileter (g/dL).
• Hepatic:
  • Bilirubin lesser than (<) upper limit of normal (ULN);
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 1.5 times ULN;
  • Participants with liver metastases may be enrolled.
• Renal:
  • Creatinine < 1.5 times normal, or creatinine clearance greater than (>) 45 milliliters per minute (mL/min). 
• Toxicity from prior therapies recovered to Grade lesser than or equal to (≤) 1 or participant's baseline. 
• Up to 4 prior systemic oncology therapy regimens for metastatic, locally recurrent, or unresectable LMS. 
• At least 4 weeks since prior radiotherapy. 
• 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.

Exclusion Criteria: 

• Received any systemic anticancer therapy including investigational agents ≤ 3 weeks (or ≤ 5 half-lives of the drug, whichever is longer) prior to registration.
• 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, for example, repeated demonstration of a QTc interval > 500 milliseconds (msec) (Long QT Syndrome [congenital]).
• Known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) positivity. 
• History of solid organ transplantation. 
• Known or suspected allergy or immediate or delayed hypersensitivity to PTC596 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 participant's ability to swallow oral medications. 
• Serious non-healing wound, ulcer, or bone fractures. 
• Major surgery, open biopsy or significant traumatic injury within 28 days of registration for protocol therapy. 
• Mucosal or internal bleeding.
• Severe pulmonary problems generally defined by need for medical intervention (for example, oxygen, medications) and/or limiting activities of daily living (generally Common Terminology Criteria for Adverse Events [CTCAE] Grade 2) or shortness of breath with limited exertion. Pulmonary conditions include, for example, chronic obstructive pulmonary disease (COPD), asthma, and hemi-pneumectomy. 
• At baseline, no drugs that are substrates, inhibitors, or inducers of cytochrome P1A2 (CYP1A2) or moderate/strong cytochrome P (CYP) inducers such as St. John's Wort, rifampicin, phenytoin, etc. 
• Prior malignancy except curatively treated carcinoma in situ of the cervix or skin cancer. 
• Known coagulopathy or bleeding diathesis. 
• 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 participant, 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 participant's history, including treated central nervous system (CNS) disease which is clinically and radiographically stable.