Sitravatinib in Treating Patients with Locally Advanced or Metastatic Liposarcoma or Other Soft Tissue Sarcomas That Cannot Be Removed by Surgery

Inclusion Criteria

• Stage 1: Histologically confirmed well-differentiated or dedifferentiated liposarcoma; if stage 1 of the Simon II stage design fails to meet its endpoint for liposarcoma patients, an additional 16 patients will be enrolled, composed of 4 each of malignant peripheral nerve sheath tumor (MPNST), synovial sarcoma, alveolar rhabdomyosarcoma and alveolar soft part sarcoma (otherwise, an additional 16 patients with well-differentiated or de-differentiated liposarcoma would be enrolled); pathology review occurs at the center enrolling the patient on this trial
• Disease must be locally advanced and unresectable or metastatic; disease which may be resected but with an associated level of morbidity deemed unacceptable by the treating clinician is considered eligible
• Patients must have measurable disease by RECIST criteria version 1.1
• Patients must evidence of disease progression, either clinically or radiographically, within the 12 weeks prior to study enrollment, as determined by the investigator enrolling the patient on the study
• Patients must have been treated with at least one prior systemic regimen for sarcoma; neoadjuvant or adjuvant systemic therapy qualify as prior therapy for the purposes of this study; there is no upper limit on previous lines of therapy received; a prior line of systemic therapy may include prior investigational agents received as part of other clinical studies
• Patients must be age 18 years or older. Because no dosing or adverse event data are currently available for MGCD516 in patients less than 18 years of age, children are excluded from the present study, but will be eligible for future pediatric trials.
• Patients must demonstrate an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Creatinine =< 1.5 times upper limit of normal OR calculated creatinine clearance > 45 mL/min * Using the lean body mass formula only (Modified Cockcroft Gault)
• Total bilirubin =< 1.5 times upper limit of normal * If transaminase elevation and/or bilirubin elevation is attributed to the presence of liver metastases, a total bilirubin =< 2.5 times the upper limit of normal and an aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times the upper limit of normal are permissible; patients with an elevated bilirubin level that is attributed to an inherited disorder, such as Gilbert’s disease, may be enrolled at the discretion of the principal investigator
• AST/ALT =< 1.5 times upper limit of normal * If transaminase elevation and/or bilirubin elevation is attributed to the presence of liver metastases, a total bilirubin =< 2.5 times the upper limit of normal and an AST and ALT =< 2.5 times the upper limit of normal are permissible; patients with an elevated bilirubin level that is attributed to an inherited disorder, such as Gilbert’s disease, may be enrolled at the discretion of the principal investigator
• Patients must demonstrate adequately controlled blood pressure at the time of study entry, as defined by a blood pressure =< 150/100 mmHg at study screening on at least one of two screenings conducted at least 24 hours apart; if blood pressure meets these guidelines on initial measurement, no subsequent measurement for screening is needed; blood pressure may be assessed by automated or manual methods by an appropriately trained clinician or nurse
• Patients must have normal left ventricular systolic function, as demonstrated by a transthoracic echocardiogram or multi-gated acquisition scan (MUGA) scan showing a normal left ventricular ejection fraction
• The effects of MGCD516 on the developing human fetus are unknown; for this reason, women of child-bearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MGCD516 administration. If patients do not agree to the above, they are not considered eligible
• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

• Patients must not have received treatment with any chemotherapy, immunotherapy, radiotherapy or an investigational agent for malignancy within the 28 days preceding study registration; patients may not have received treatment with nitrosureas or mitomycin within the 42 days prior to study registration; patients may not have received treatment with a small molecule targeted agent (including off-label or investigational use) within 14 days preceding study registration, provided this represents at least 7 half-lives for that agent; toxic effects from any prior therapy (except alopecia) must have resolved to grade 1 or less according to National Cancer Institute (NCI) CTCAE version (v)4.0 or to the patient’s baseline by the time of registration
• Patients may not be receiving any other investigational agent for any purpose concurrently; patients may not require ongoing treatment with (a) gastric pH modifying medications including proton pump inhibitors or H2 blockers (patients may switch to antacids), (b) medications which are known to be sensitive substrates or substrates with a narrow therapeutic index for the P-gp and BCRP transporters and/or (c) medications known to cause corrected QT (QTc) prolongation with risk of Torasades
• Patients may not have a history of allergic reaction or hypersensitivity to microcrystalline cellulose (Avicel PH302) or polysorbate 80 (Tween 80), which are components of the drug product MGCD516
• Patients may not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled diabetes mellitus or uncontrolled psychiatric illness that would limit compliance with study requirements in the opinion of the principal investigator; additionally, patients must be free of any impairment in the ability to swallow and absorb the oral study drug
• Patients may not be pregnant or nursing; pregnant women are excluded from this study because the teratogenic effects of MGCD516 have not been adequately studied; a negative pregnancy test must be documented 7 days or less prior to registration; because there is an unknown but potential risk for adverse events to nursing infants secondary to treatment of the mother with MGCD516, breastfeeding must be discontinued prior to registration for this clinical trial
• Patients may not have known human immunodeficiency virus (HIV) infection; HIV-positive patients on combination antiretroviral therapy are ineligible because these patients are at increased risk of lethal infections when treated with potentially marrow suppressive therapy; although marrow suppression was not an observed toxicity in the phase 1 trial of this agent, this side effect has been observed with other pan-receptor tyrosine kinase inhibitors