Itacitinib in Treating Patients With Refractory Metastatic/Advanced Sarcomas

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03670069

Collaborator

Incyte Corporation (Industry)

Enrollment

Location

Arm

63.1

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Itacitinib Other: Laboratory Biomarker Analysis	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study Examining the Impact of the Jak1 Inhibitor Itacitinib on the Sarcoma Tumor Immune Microenvironment

Actual Study Start Date :

Sep 30, 2019

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (itacitinib) Patients receive itacitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Itacitinib Given PO Other Names: 1334298-90-6 3-Azetidineacetonitrile INCB039110 Other: Laboratory Biomarker Analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (itacitinib)

Patients receive itacitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Itacitinib

Given PO

Other Names:

1334298-90-6

3-Azetidineacetonitrile

INCB039110

Other: Laboratory Biomarker Analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Difference in the percentage of cells which are immune inhibitory (CD11B+, CD163+) macrophages from pre-treatment to first post-treatment biopsy [From baseline to 2 years]
Evaluation of the change in percentages of cells against the null hypothesis of no difference will be performed using a 1-sided t-test at the 0.05 level.

Secondary Outcome Measures

Incidence of adverse events [Up to 2 years]
Will be graded according to Common Terminology Criteria for Adverse Events version 5.0. The frequency and severity of toxicities will be evaluated by proportions and associated 95% confidence intervals.
Progression-free survival rate [At 6 months]
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Distributions and percentages at landmark times for time to event outcomes will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the method of Brookmeyer-Crowley. With 12 LMS patients, binary proportions can be estimated to within 29% with 95% confidence. With 8 (SS or MRCL) and PUS, respectively, binary proportions can be estimated to within 36% with 95% confidence.
Median overall survival [At 12 months]
Distributions and percentages at landmark times for time to event outcomes will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the method of Brookmeyer-Crowley. With 12 LMS patients, binary proportions can be estimated to within 29% with 95% confidence. With 8 (SS or MRCL) and PUS, respectively, binary proportions can be estimated to within 36% with 95% confidence.
Clinical benefit rate (complete response [CR]+ partial response [PR]+stable disease [SD]) [At 12 weeks]
CR and PR will be defined as per RECIST 1.1 Distributions and percentages at landmark times for time to event outcomes will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the method of Brookmeyer-Crowley. With 12 LMS patients, binary proportions can be estimated to within 29% with 95% confidence. With 8 (SS or MRCL) and PUS, respectively, binary proportions can be estimated to within 36% with 95% confidence.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 (chondrosarcoma subjects do not have prior treatment requirements and 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 =< 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+ 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