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Itacitinib in Treating Patients With Refractory Metastatic/Advanced Soft Soft Tissue Sarcomas

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ClinicalTrials.gov Identifier: NCT03670069
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : December 4, 2020
Sponsor:
Collaborators:
Incyte Corporation
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Brief Summary:
This pilot phase II trial studies how well itacitinib works in treating patients with soft tissue sarcomas that do not respond to treatment (refractory) and have spread to other parts of the body (advanced/metastatic). Itacitinib may cause changes in the immune system and the body's immune response to cancer, which 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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 30, 2019
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2022


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




Primary Outcome Measures :
  1. Difference in the percentage of cells which are immune inhibitory (CD11B+, CD163+) macrophages from pre-treatment to first post-treatment biopsy [ Time Frame: 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 :
  1. Incidence of adverse events [ Time Frame: 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.

  2. Progression-free survival rate [ Time Frame: 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.

  3. Median overall survival [ Time Frame: 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.

  4. Clinical benefit rate (complete response [CR]+ partial response [PR]+stable disease [SD]) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have a histologically confirmed diagnosis of soft tissue sarcoma with one of the following subtypes:

    • Cohort 1: Leiomyosarcoma
    • Cohort 2: Undifferentiated pleiomorphic sarcoma
    • Cohort 3: Synovial sarcoma or myxoid/round cell liposarcoma
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03670069


Contacts
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Contact: Roxanne Moore 206-606-6425 romoore@seattlecca.org

Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Roxanne Moore    206-606-6425    romoore@seattlecca.org   
Principal Investigator: Seth Pollack         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Incyte Corporation
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Seth Pollack Fred Hutchinson Cancer Research Center
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Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT03670069    
Other Study ID Numbers: RG9218021
NCI-2018-00615 ( Registry Identifier: CTRP )
9715 ( Other Identifier: FHCRC )
5P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: September 13, 2018    Key Record Dates
Last Update Posted: December 4, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sarcoma
Leiomyosarcoma
Liposarcoma
Sarcoma, Synovial
Histiocytoma, Malignant Fibrous
Liposarcoma, Myxoid
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Muscle Tissue
Neoplasms, Adipose Tissue
Neoplasms, Connective Tissue
Histiocytoma
Neoplasms, Fibrous Tissue