We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study on TSR-042 in Advanced Clear Cell Sarcoma (ACCeSs)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04274023
Recruitment Status : Recruiting
First Posted : February 18, 2020
Last Update Posted : November 1, 2021
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Italian Sarcoma Group

Brief Summary:
Phase II,single arm study designed to explore the activity of TSR-042, an immunotherapy agent, in patients with a diagnosis of advanced or metastatic clear cell sarcoma (CCS).

Condition or disease Intervention/treatment Phase
Sarcoma, Clear Cell Drug: TSR-042 Phase 2

Detailed Description:
Phase II, single arm, not randomized, European multicentric study designed to explore the activity of TSR-042, a human monoclonal anti-PD-1 inhibitor, in a population of patients with a diagnosis of advanced/metastatic clear cell sarcoma (CCS).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study on TSR-042 in Advanced Clear Cell Sarcoma
Actual Study Start Date : February 19, 2021
Estimated Primary Completion Date : May 1, 2024
Estimated Study Completion Date : May 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TSR-042 arm
TSR-042 at a dose of 500 mg in IV infusion (given over t30-minutes) every 21 days for the first 4 doses, followed by 1.000 mg on day 1 of every 42 day.
Drug: TSR-042
TSR-042 is an IgG4 humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2.




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: At week 12 ]
    Response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1


Secondary Outcome Measures :
  1. Immune-related RECIST (ir-RECIST) response rate [ Time Frame: At weeks 6, 12, 24, 36, 48, 60, 72, 84, 96 ]
    Response rate according ir-RECIST criteria

  2. Choi criteria response rate [ Time Frame: At weeks 6, 12, 24, 36, 48, 60, 72, 84, 96 ]
    Response rate according Choi criteria

  3. Progression Free Survival (PFS) [ Time Frame: At 3 and 5 years ]
    Survival without disease progression

  4. Overall Survival [ Time Frame: At 3 and 5 years ]
    Proportion of patients who are still alive at 36 and 60 months after have started the treatment

  5. Clinical Benefit Rate [ Time Frame: Month 6 ]
    Proportion of patients who experienced Complete Response, Progression Response or Stable Disease for over 6 months

  6. Adverse events related to the treatment [ Time Frame: Week 3, week 6, week 9, week 12, week 18, week 24, week 36, week 48, week 60, week 72 ]
    Safety in term of grading of adverse event is evaluate from the firs treatment dose throughout the study according to CTCAE 5.0

  7. Growth Modulation Index (GMI) [ Time Frame: At weeks 6, 12, 24, 36, 48, 60, 72, 84, 96 ]
    Correlation between response and prior disease medical treatment: ratio of time to progression with the nth line of therapy to the those with the n-1th line.

  8. Quality of Life according the 30 questions European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [ Time Frame: Day1 Cycle 2, Day 1 Cycle 3, Every 3 cycles (Day1Cyle6, Day1Cycle 9, …) and through study completion, an average of 1 year ]
    Evaluation of the quality of life collected with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30

  9. Quality of Life according the questionnaire Euro Quality Of Life 5 Domains (EQ-5D) [ Time Frame: Day1 Cycle 2, Day 1 Cycle 3, Every 3 cycles (Day1Cyle6, Day1Cycle 9, …) and through study completion, an average of 1 year ]
    Evaluation of the quality of life collected with Euro Quality Of Life 5 Domains (EQ-5D)

  10. Safety according the Patient Reported Outcome according Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Day1 Cycle 2, Day 1 Cycle 3, Every 3 cycles (Day1Cyle6, Day1Cycle 9, …) and through study completion, an average of 1 year ]
    Evaluation of the quality of safety reported by the patient with the PRO-CTCAE


Other Outcome Measures:
  1. Expression level of PD1 and PDL1 at pre-treatment evaluated on cancer cells and in tumor infiltrating myeloid cells [ Time Frame: Day1 (pre-treatment) ]
    Analysis of immune contexture in pretreatment tumor tissue.

  2. Frequency in the expression of myeloid-derived suppressor cells in peripheral blood mononuclear cell [ Time Frame: Day1, day15, day45 of treatment and through study completion, an average of 1 year ]
    Immunological monitoring of peripheral blood immune subsets, to evaluate the systemic immunological status of patients,

  3. Frequency in the expression of anti-tumor immune cells in PBMC collected at baseline and during TSR-042. [ Time Frame: Day1, day15, day45 of treatment and through study completion, an average of 1 year ]
    Immunological monitoring of peripheral blood immune subsets, to evaluate the systemic immunological status of patients,



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Written informed consent
  2. Histological centrally confirmed diagnosis of clear cell sarcoma
  3. Availability of archived tumor tissue block, or 15 slides.
  4. Locally advanced disease
  5. Measurable disease based on RECIST 1.1
  6. Patient can be naive or previously treated with 1 or 2 systemic regimens given for recurrent and/or metastatic disease
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
  8. Adequate bone marrow function
  9. Adequate organ function
  10. Cardiac ejection fraction ≥50%
  11. At least 18 years of age on day of signing informed consent.
  12. Non-pregnant female patients
  13. Non-ot breastfeed during the study for 90 days after the last dose of study treatment.
  14. Male participant agrees to use an adequate method of contraception
  15. No history of arterial and/or venous thromboembolic event within the previous 12 months.
  16. Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
  17. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

  1. Participant must not be simultaneously enrolled in any interventional clinical trial
  2. Previous treatment with any non-investigational agents within 14 days of first day of study drug dosing.
  3. Must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy
  4. Other primary malignancy with <5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse
  5. Previous treatment with radiation therapy within 14 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  6. Has known active central nervous system (CNS) metastases, leptomeningeal metastases, and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable, have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  7. Has active, non-infectious pneumonitis
  8. Has an active infection requiring systemic therapy
  9. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agents
  10. Has received a live vaccine within 30 days of planned start of study therapy
  11. Major surgery within 3 weeks prior to study entry
  12. Any one of the following currently or in the previous 6 months:

Myocardial infarction, congenital long QT syndrome, Torsades de Pointes, arrhythmias right bundle branch block and left anterior hemiblock unstable angina coronary/peripheral artery bypass graft, symptomatic congestive heart failure New York Heart Association Class III or IV, cerebrovascular accident, or transient ischemic attack symptomatic pulmonary embolism. Ongoing cardiac dysrhythmias of Grade >=3, atrial fibrillation of any grade,or QTcF interval >470 msec 14. Severe and/or uncontrolled medical disease 15. Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy 16. Participant has a diagnosis of immunodeficiency or has receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy 17. Any known active hepatitis B or hepatitis C 18. Any known history of human immunodeficiency virus 19. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 20. Expected non-compliance to medical regimens 21. Known history of interstitial lung disease 22. Active autoimmune disease that has required systemic treatment in the past 2 years 23. Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma


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): NCT04274023


Contacts
Layout table for location contacts
Contact: Silvia Stacchiotti, MD 39022390 ext 2804 silvia.stacchiotti@istitutotumori.mi.it

Locations
Layout table for location information
France
Centre Leon Berard Not yet recruiting
Lyon, France, 69008
Contact: Jean Y. Blay         
Principal Investigator: Jean Y. Blay, MD         
Italy
Fondazione IRCSS Istituto Nazionale dei Tumori Recruiting
Milan, Italy, 20133
Contact: Silvia Stacchiotti, MD    +39022390    silvia.stacchiotti@istitutotumori.mi.it   
Principal Investigator: Silvia Stacchiotti, MD         
Spain
Hospital Virgen del Rocío Not yet recruiting
Sevilla, Andalucía, Spain, 41013
Contact: Javier M. Broto, MD       jmartin@mustbesevilla.org   
Principal Investigator: Javier M. Broto, MD         
Sponsors and Collaborators
Italian Sarcoma Group
GlaxoSmithKline
Investigators
Layout table for investigator information
Principal Investigator: Silvia Stacchiotti, MD Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Publications:
Layout table for additonal information
Responsible Party: Italian Sarcoma Group
ClinicalTrials.gov Identifier: NCT04274023    
Other Study ID Numbers: ISG-ACCeSs
First Posted: February 18, 2020    Key Record Dates
Last Update Posted: November 1, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Italian Sarcoma Group:
advanced clear cell sarcoma
anti-PDL1
Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma
Sarcoma, Clear Cell
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue