AzTrials
AzTrials

Metastatic LeiomyosarcomaPhase 1NCT03670069

Itacitinib in Treating Patients With Refractory Metastatic/Advanced Sarcomas

A Phase 1 study testing Itacitinib and Laboratory Biomarker Analysis in people with Metastatic Leiomyosarcoma and Metastatic Synovial Sarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Itacitinib and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
30 Sep 2019to 6 May 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 27Show fewer
  • 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
  • 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

Who cannot join

  • 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)
Show all 13Show fewer
  • 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 locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Itacitinib, Laboratory Biomarker Analysis
Medical subject headings
Leiomyosarcoma, Sarcoma, Synovial, Histiocytoma, Malignant Fibrous, Liposarcoma, Myxoid, Sarcoma, Chondrosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ItacitinibDrug

    Also called 1334298-90-6, 3-Azetidineacetonitrile, INCB039110

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT03670069
Study groupRoleWhat they receive
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.
Receives: Drug: Itacitinib; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From baseline to 2 years

Secondary outcomes (4)

  1. Incidence of adverse events

    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.

    Measured: Up to 2 years

  2. Progression-free survival rate

    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.

    Measured: At 6 months

  3. Median overall survival

    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.

    Measured: At 12 months

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

    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.

    Measured: At 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2018
  2. Study start30 Sep 2019
  3. Primary completion4 Mar 2023
  4. Study completion6 May 2024

Why it stopped: The study was terminated early with 27 out of 28 planned subjects enrolled. This decision was multifactorial, including slow enrollment in the last remaining cohort and a lack of evidence of clinical benefit.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03670069
Sponsor's protocol ID
RG9218021
Other IDs
NCI-2018-00615, 9715
Status last verified
May 2024
First submitted
12 Sep 2018
Last updated
8 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Itacitinib and Laboratory Biomarker Analysis in people with Metastatic Leiomyosarcoma and Metastatic Synovial Sarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated early with 27 out of 28 planned subjects enrolled. This decision was multifactorial, including slow enrollment in the last remaining cohort and a lack of evidence of clinical benefit.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03670069.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in