Itacitinib in Treating Patients With Refractory Metastatic/Advanced Sarcomas
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
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.
Full description
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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Subjects >= 18 years old
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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)
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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
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All ongoing toxicities related to prior therapies must be resolved to grade 1 or better (except alopecia)
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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)
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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.
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Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range mg/dL
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Aspartate aminotransferase (AST) =< 2.5 x ULN and alanine aminotransferase (ALT) levels =< 2.5 x ULN
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Alkaline phosphatase < 2.5 x ULN
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Serum creatinine =< 1.5 x ULN
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Calculated creatinine clearance >= 30 mL/min using the Cockcroft-Gault formula may be included
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Absolute neutrophil count (ANC) >= 1.5 × 10^9/L
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Platelet count >= 100 x 10^9/L; transfusion is permitted as clinically indicated
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Hemoglobin >= 9 g/dL
* Transfusion is permitted as clinically indicated
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Subjects must have a life expectancy >= 6 months, as determined by the treating physician
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Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofksy performance status >= 60
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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
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Ability to understand and sign informed consent document
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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
Trial design
Primary purpose
Allocation
Interventional model
Masking
27 participants in 1 patient group
Trial contacts and locations
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Central trial contact
Roxanne Moore
Data sourced from clinicaltrials.gov
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