Itacitinib in Treating Patients With Refractory Metastatic/Advanced Sarcomas

NCT03670069 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: RG9218021NCI-2018-006159715
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Difference in the percentage of cells which are immune inhibitory (CD11B+, CD163+) macrophages from pre-treatment to first post-treatment biopsy

  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.

  From baseline to 2 years

Secondary Outcomes (4)

• Incidence of adverse events

  Up to 2 years

• Progression-free survival rate

  At 6 months

• Median overall survival

  At 12 months

• Clinical benefit rate (complete response [CR]+ partial response [PR]+stable disease [SD])

  At 12 weeks

Study Arms (1)

Treatment (itacitinib)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis

Interventions

Itacitinib DRUG

Given PO

Also known as: 1334298-90-6, 3-Azetidineacetonitrile, INCB039110

Treatment (itacitinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (itacitinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Incyte Corporation: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leiomyosarcoma; Sarcoma, Synovial; Histiocytoma, Malignant Fibrous; Liposarcoma, Myxoid; Sarcoma; Chondrosarcoma

Interventions

itacitinib; baricitinib; INCB039110

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Histiocytoma; Neoplasms, Fibrous Tissue; Liposarcoma; Neoplasms, Adipose Tissue

Study Officials

• Lee Cranmer

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 13, 2018
• Study Start: September 30, 2019
• Primary Completion: March 4, 2023
• Study Completion: May 6, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)