itacitinib in treating patients with refractory metastatic/advanced sarcomas

Conditions: Metastatic Leiomyosarcoma; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Advanced Myxoid Liposarcoma; Advanced Soft Tissue Sarcoma; Metastatic Myxoid Liposarcoma; Metastatic Round Cell Liposarcoma; Metastatic Soft Tissue Sarcoma; Refractory Leiomyosarcoma; Refractory Myxoid Liposarcoma; Refractory Round Cell Liposarcoma; Refractory Soft Tissue Sarcoma; Refractory Synovial Sarcoma; Refractory Undifferentiated Pleomorphic Sarcoma; Advanced Leiomyosarcoma; Advanced Synovial Sarcoma; Advanced Undifferentiated Pleomorphic Sarcoma; Metastatic Chondrosarcoma

Summary: this pilot phase i trial studies how well itacitinib works in treating patients with sarcomas that do not respond to treatment (refractory) and have spread to other parts of the body (advanced/metastatic). itacitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

outline: patients receive itacitinib orally (po) once daily (qd) on days 1-28. cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed up at 7 and 30 days, every 12 weeks from baseline for up to 1 year, and then every 6 months thereafter.

Eligibility criteria:
inclusion criteria: * subjects \>= 18 years old * must have a histologically confirmed diagnosis of sarcoma with one of the following subtypes: * cohort 1: leiomyosarcoma * cohort 2: undifferentiated pleiomorphic sarcoma * cohort 3: synovial sarcoma or myxoid/round cell liposarcoma * cohort 4: chondrosarcoma (all subtypes of chondrosarcoma are allowed) * subjects enrolling to cohorts 1, 2, or 3 must have received at least two prior lines of systemic therapy. subjects enrolling to cohort 4 only may have received any number of prior lines of systemic therapy or may be treatment naïve * all ongoing toxicities related to prior therapies must be resolved to grade 1 or better (except alopecia) * subjects must have one or more measurable lesions, as determined by response evaluation criteria in solid tumors (recist) version (v)1.1 assessed by computed tomography (ct) or magnetic resonance imaging (mri) * subjects must have at least one superficial lesion accessible for multiple biopsies; the tumor being biopsied cannot have been previously targeted for radiation therapy or have previously received intra-lesional treatment \* note: superficial lesions previously targeted with radiation therapy that have demonstrated significant new growth via radiological imaging may be targeted for biopsy, with sponsor-investigator approval. * total bilirubin level =\< 1.5 x the upper limit of normal (uln) range mg/dl * aspartate aminotransferase (ast) =\< 2.5 x uln and alanine aminotransferase (alt) levels =\< 2.5 x uln * alkaline phosphatase \< 2.5 x uln * serum creatinine =\< 1.5 x uln * calculated creatinine clearance \>= 30 ml/min using the cockcroft-gault formula may be included * absolute neutrophil count (anc) \>= 1.5 × 10\^9/l * platelet count \>= 100 x 10\^9/l; transfusion is permitted as clinically indicated * hemoglobin \>= 9 g/dl \* transfusion is permitted as clinically indicated * subjects must have a life expectancy \>= 6 months, as determined by the treating physician * eastern cooperative oncology group (ecog) performance status =\ = 60 * male or non-pregnant and non-breast feeding female: * females of child-bearing potential must agree to use highly effective contraception without interruption from initiation of therapy and while on study medication and have a negative serum pregnancy test (beta - human chorionic gonadotropin \[hcg\]) result at screening and agree to ongoing pregnancy testing during the course of the study, and at the end of study treatment; a highly effective method of contraception is defined as one that results in a low failure rate (that is, \< 1% per year), when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner * male subjects must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study * ability to understand and sign informed consent document * willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures exclusion criteria: * known active, uncontrolled, or symptomatic central nervous system (cns) metastases; a subject with controlled and asymptomatic cns metastases may participate in this study; as such, the subject must have completed any prior treatment for cns metastases \>= 28 days (including radiotherapy and/or surgery) prior to the start of treatment in this study and should not be receiving chronic corticosteroid therapy for cns metastases; subjects with known cns metastases must be confirmed radiographically stable by at least one imaging study, at least 28 days from last treatment * receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 2 weeks of enrollment * prior treatment with a drug targeting jak1, jak1/2 or stat3 inhibitor; food and drug administration (fda) approved small molecule tyrosine kinase inhibitors (tkis) not specifically designed to target this pathway are okay (e.g. pazopanib, sunitinib, sorafenib) * known, active drug or alcohol abuse * pregnant or lactating females * active or recent infection requiring systemic anti-infective treatment that was completed =\< 14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory infection) * uncontrolled or concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * oral steroid usage within =\< 14 days prior to enrollment * known inflammatory or autoimmune disease which requires patient to occasionally require high dose oral steroids * subjects with known, active human immunodeficiency virus (hiv) infection (subjects with undetectable viral load and normal cd4+ t-cell count are permitted) * inability to swallow food or tablets, or significant gastrointestinal disorder that, in the opinion of the investigator, could interfere with absorption of the study drug * previous reaction to any component of itacitinib or known hypersensitivity to the active substance or any of the excipients * subjects with a sarcoma which has other, defined treatments or biology distinctly different from those of soft tissue sarcomas in general; including, but not limited to, ewing's sarcoma, rhabdomyosarcoma, gastrointestinal stromal tumors, kaposi's sarcoma, wilm's tumor