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.
Inclusion Criteria:
- 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 must have received at least two prior lines of systemic therapy
- 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 =< 2 or Karnofksy
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+ 1-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
