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Myxoid LiposarcomaPhase 2NCT03397186

Immune Changes Following Trabectedin in Patients With Metastatic or Unresectable Sarcoma

A Phase 2 study testing Biopsy, Laboratory Biomarker Analysis and Trabectedin in people with Myxoid Liposarcoma and Round Cell Liposarcoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This research trial studies the immune changes following trabectedin in patients with sarcoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Laboratory Biomarker Analysis and Trabectedin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
19 Jun 2018to 1 May 2021
Phase
Phase 2
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 must have a diagnosis of advanced (unresectable or metastatic) sarcoma, for which trabectedin treatment is indicated
  • Subjects must have received prior anthracycline treatment; subjects who failed to tolerate it or for whom it is not clinically appropriate in the opinion of their treating physician may be included
  • All ongoing toxicities related to prior therapy must be resolved to grade 1 or better (except alopecia)
  • Total bilirubin level =< upper limit of normal (ULN) mg/dL
  • Aspartate aminotransferase (AST) =< 2.5 x ULN
  • Alanine aminotransferase (ALT) =< 2.5 x ULN
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  • 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
  • Creatine phosphokinase (CPK) =< 2.5 x ULN
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dL
  • Baseline left ventricular ejection fraction (LVEF) 45% or greater (by echocardiogram or multigated acquisition scan [MUGA] study) and no evidence of New York Heart Association class ll to IV heart failure
  • Subjects with lesions safely accessible for biopsy, in the opinion of the treating physician and/or interventional radiology
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Ability to understand and sign informed consent
  • Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures

Who cannot join

  • Subjects for whom treatment with trabectedin is not indicated
  • All subjects with brain metastases, except those meeting the following criteria:
  • Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
  • No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
  • Subjects must be either off steroids or on a stable or decreasing dose of =< 10 mg daily prednisone (or equivalent), excluding dexamethasone given as pre-treatment for trabectedin
  • Prior organ transplantation, including allogeneic stem cell transplantation
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  • Subjects with abnormal prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) or bleeding diathesis
  • Prior treatment with trabectedin
  • Prior chemotherapy within 2 weeks; prior immunotherapy or biologic therapy within 4 weeks; prior radiation therapy within 3 weeks
  • Significant acute or chronic infections as these may affect the immune response including:
  • Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Positive test for hepatitis B virus (HBV) surface antigen and / or confirmatory hepatitis C virus (HCV) ribonucleic acid (RNA) (if anti-HCV antibody tested positive)
  • Subjects on chronic therapy with any systemic immunosuppressant (not counting inhaled steroids or steroid creams) for any reason, including autoimmune disease
  • Known alcohol or drug abuse
  • Subjects who are breast feeding
  • Subjects with known hypersensitivity including anaphylaxis to trabectedin
  • Myocardial infarction (infarct) within 6 months before enrollment, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

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: An Analysis of the Changes in the Sarcoma Tumor Immune Microenvironment Following Trabectedin

This research trial studies the immune changes following trabectedin in patients with sarcoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Analyzing tumor tissue may help to understand the changes in immune cells in or around the tumor or if there is an increase in immune cells in the tumor after receiving trabectedin.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Percentage of tumor tissue in pre- and post-treatment biopsies comprised of T-cells, as determined by flow cytometry.

SECONDARY OBJECTIVES:

  1. To explore additional potential biomarkers including: numbers of tumor associated macrophage (TAM) in tumor II. To explore additional potential biomarkers including: phenotype (classically activated macrophages [M1] versus [vs] alternatively activated macrophages [M2]) as characterized by CD163, CD115, CD206 on infiltrating TAM.

III. To explore additional potential biomarkers including: phenotype of T cells infiltrating tumor (CD4, CD8, markers of CD4 phenotype including FoxP3 and memory).

IV. To explore additional potential biomarkers including: expression T cell inhibitory markers (PD-1, CTLA-4, TIM3).

  1. To explore additional potential biomarkers including: recognition of autologous tumor by expanded tumor infiltrating lymphocyte lines.

VI. To explore additional potential biomarkers including: in tumor infiltrating lymphocyte (TIL) expanded from myxoid/round cell liposarcomas, recognition of cancer testis antigens.

OUTLINE:

Patients undergo a biopsy at baseline and then receive trabectedin for up to 4 cycles. Beginning 1 week after completion of cycle 2 and prior to cycle 3, patients undergo a second biopsy. Patients who achieve clinical benefit (complete response [CR], partial response [PR], stable disease [SD]) after the first post-treatment scan and who continue trabectedin for 4 cycles undergo a third biopsy after cycle 4.

After completion of study, patients are followed up for 30 days.

Being tested
Biopsy, Laboratory Biomarker Analysis, Trabectedin
Medical subject headings
Liposarcoma, Myxoid, Sarcoma

What participants receive

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

  • BiopsyProcedure or surgery

    Also called Bx

    Undergo biopsy

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • TrabectedinDrug

    Also called Ecteinascidin, ecteinascidin 743, ET-743, Yondelis

    Given as standard of care

Study groups in NCT03397186
Study groupRoleWhat they receive
Basic science (trabectedin, biopsy)OtherPatients undergo a biopsy at baseline and then receive trabectedin for up to 4 cycles. Beginning 1 week after completion of cycle 2 and prior to cycle 3, patients undergo a second biopsy. Patients who achieve clinical benefit (CR, PR, SD) after the first post-treatment scan and who continue trabectedin for 4 cycles undergo a third biopsy after cycle 4.
Receives: Procedure: Biopsy; Other: Laboratory Biomarker Analysis; Drug: Trabectedin

What is being measured

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

  1. Percentage change of T cells (CD3+) by flow cytometry

    Analysis will be performed using a Wilcoxon matched-pairs assigned rank test as these will be paired samples where parametric distribution cannot be assumed. T cell receptor (TCR) sequencing, immunohistochemistry and gene expression analysis will all be used in order to confirm the primary endpoint.

    Measured: Baseline up to 4 weeks

Secondary outcomes (4)

  1. Expression of inhibitory ligands including PD-1, CTLA-4, LAG-3 on infiltrating T cells

    Gene expression will be analyzed using differential cluster analysis in order to look for patterns and gene groups that are differentially expressed in the post-treatment samples and such gene groups will be represented by heatmaps in order to illustrate this quantitative information. TCR fraction, clonality, and maximum (max) frequency will be compared between pre and post treatment samples.

    Measured: Up to 4 weeks

  2. CD8+ or CD4+ phenotype of infiltrating T cells

    Gene expression will be analyzed using differential cluster analysis in order to look for patterns and gene groups that are differentially expressed in the post-treatment samples and such gene groups will be represented by heatmaps in order to illustrate this quantitative information. TCR fraction, clonality, and max frequency will be compared between pre and post treatment samples.

    Measured: Up to 4 weeks

  3. Type 1 helper cell (Th1) versus (vs.) type 2 helper cell (Th2) phenotype of infiltrating T cells based on expression of CCR5 and CXCR3

    Gene expression will be analyzed using differential cluster analysis in order to look for patterns and gene groups that are differentially expressed in the post-treatment samples and such gene groups will be represented by heatmaps in order to illustrate this quantitative information. TCR fraction, clonality, and max frequency will be compared between pre and post treatment samples.

    Measured: Up to 4 weeks

  4. Infiltrating tumor associated macrophage number

    Measured: Up to 4 weeks

Timeline

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

  1. First posted11 Jan 2018
  2. Study start19 Jun 2018
  3. Primary completion1 Jan 2021 (estimated)
  4. Study completion1 May 2021 (estimated)

Why it stopped: Administrative

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 2
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03397186
Sponsor's protocol ID
9769
Other IDs
NCI-2017-02298, 9769, P30CA015704, RG9217026
Status last verified
Sep 2019
First submitted
5 Jan 2018
Last updated
10 Sep 2019
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Laboratory Biomarker Analysis and Trabectedin in people with Myxoid Liposarcoma and Round Cell Liposarcoma, 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 21 inclusion and 17 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: withdrawn, as of the sponsor's last update on 10 Sep 2019. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 withdrawn before enrolling participants, so there are no results.

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?

Percentage change of T cells (CD3+) by flow cytometry (time frame: Baseline up to 4 weeks). 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 NCT03397186.

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 10 Sep 2019.

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