- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03397186
Immune Changes Following Trabectedin in Patients With Metastatic or Unresectable Sarcoma
An Analysis of the Changes in the Sarcoma Tumor Immune Microenvironment Following Trabectedin
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Percentage of tumor tissue in pre- and post-treatment biopsies comprised of T-cells, as determined by flow cytometry.
SECONDARY OBJECTIVES:
I. 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).
V. 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.
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Basic science (trabectedin, biopsy)
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 (CR, PR, SD) after the first post-treatment scan and who continue trabectedin for 4 cycles undergo a third biopsy after cycle 4.
|
Correlative studies
Undergo biopsy
Other Names:
Given as standard of care
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage change of T cells (CD3+) by flow cytometry
Time Frame: Baseline up to 4 weeks
|
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.
|
Baseline up to 4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Expression of inhibitory ligands including PD-1, CTLA-4, LAG-3 on infiltrating T cells
Time Frame: Up to 4 weeks
|
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.
|
Up to 4 weeks
|
CD8+ or CD4+ phenotype of infiltrating T cells
Time Frame: Up to 4 weeks
|
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.
|
Up to 4 weeks
|
Type 1 helper cell (Th1) versus (vs.) type 2 helper cell (Th2) phenotype of infiltrating T cells based on expression of CCR5 and CXCR3
Time Frame: Up to 4 weeks
|
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.
|
Up to 4 weeks
|
Infiltrating tumor associated macrophage number
Time Frame: Up to 4 weeks
|
Up to 4 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 9769 (Fred Hutch/University of Washington Cancer Consortium)
- P30CA015704 (U.S. NIH Grant/Contract)
- NCI-2017-02298 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- RG9217026 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myxoid Liposarcoma
-
Maria Sklodowska-Curie National Research Institute...Active, not recruiting
-
Johnson & Johnson Pharmaceutical Research & Development...PharmaMarCompletedLiposarcoma,MyxoidFrance, United States, Germany
-
GlaxoSmithKlineCompleted
-
The Netherlands Cancer InstituteUnknownMyxoid Liposarcoma of Soft TissueNetherlands, United Kingdom, Norway, United States, Denmark
-
Mario Negri Institute for Pharmacological ResearchFondazione IRCCS Istituto Nazionale dei Tumori, Milano; Humanitas Hospital,...RecruitingLiposarcoma, Myxoid | Liposarcoma, Dedifferentiated | Liposarcoma, Round CellItaly
-
The Netherlands Cancer InstituteM.D. Anderson Cancer Center; Mayo Clinic; Radboud University Medical Center; Aarhus... and other collaboratorsRecruitingMyxoid LiposarcomaNetherlands
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI); Daiichi Sankyo, Inc.Completed
-
Systems Medicine LLCUnknown
-
Fred Hutchinson Cancer CenterIncyte CorporationActive, not recruitingRefractory Soft Tissue Sarcoma | Metastatic Leiomyosarcoma | Metastatic Synovial Sarcoma | Metastatic Undifferentiated Pleomorphic Sarcoma | Advanced Soft Tissue Sarcoma | Metastatic Soft Tissue Sarcoma | Advanced Synovial Sarcoma | Metastatic Chondrosarcoma | Advanced Leiomyosarcoma | Metastatic Myxoid... and other conditionsUnited States
-
GlaxoSmithKlineTerminatedNeoplasmsUnited States, Germany, Netherlands, Canada, Australia, Sweden
Clinical Trials on Laboratory Biomarker Analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Localized OsteosarcomaUnited States