Clinical Trials /

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

NCT03670069

Description:

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.

Related Conditions:
  • Leiomyosarcoma
  • Myxoid Liposarcoma
  • Round Cell Liposarcoma
  • Synovial Sarcoma
  • Undifferentiated Pleomorphic Sarcoma
Recruiting Status:

Suspended

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Itacitinib in Treating Patients With Refractory Metastatic/Advanced Soft Soft Tissue Sarcomas
  • Official Title: A Pilot Study Examining the Impact of the Jakl Inhibitor Itacitinib on the Sarcoma Tumor Immune Microenvironment

Clinical Trial IDs

  • ORG STUDY ID: RG9218021
  • SECONDARY ID: NCI-2018-00615
  • SECONDARY ID: 9715
  • SECONDARY ID: 5P30CA015704
  • NCT ID: NCT03670069

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

Interventions

DrugSynonymsArms
Itacitinib1334298-90-6, 3-Azetidineacetonitrile, INCB039110Treatment (itacitinib)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (itacitinib)ExperimentalPatients receive itacitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Itacitinib

Eligibility 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

          -  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, Sutent,
             sorafenib are okay)

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure:Incidence of adverse events
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Progression-free survival rate
Time Frame:At 6 months
Safety Issue:
Description: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.
Measure:Median overall survival
Time Frame:At 12 months
Safety Issue:
Description: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.
Measure:Clinical benefit rate (complete response [CR]+ partial response [PR]+stable disease [SD])
Time Frame:At 12 weeks
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

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