search
Back to results

Pazopanib With or Without Pembrolizumab for Metastatic Soft Tissue Sarcoma

Primary Purpose

Soft Tissue Sarcoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
pembrolizumab, pazopanib
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma focused on measuring Sarcoma, Pembrolizumab, Pazopanib

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Histologically confirmed Soft Tissue Sarcoma(STS) progression to 1 or 2 (less than 3) prior chemotherapy : Exclude pazopanib-resistant subtype - embryonal rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing tumours, primitive neuroectodermal tumour, gastrointestinal stromal tumour, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma, and liposarcoma Age > 19 years at time of study entry. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 7 days before screening) Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 Adequate normal organ and marrow function as defined below Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥ 1500 per mm3 Platelet count ≥ 100,000 per mm3 Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). Aspartate Aminotransferase (AST, SGOT)/Alanine Aminotransferase (ALT, SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN Creatinine≤1.5 x ULN or Measured or calculated(CrCl should be calculated per institutional standard) creatinine clearance(GFR can also be used in place of creatinine or CrCl) ≥ 1.5 x institutional ULN International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) : ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. A male or female participant must agree to use a contraception as detailed in Appendix 2 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days after the last dose of study treatment. Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Exclusion Criteria: Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug Any previous treatment with a Programmed Death-1(PD1) or Programmed Death-Ligand1(PD-L1) inhibitor, anti-PD-L2 agent, stimulatory/co-inhibitory T-cell receptor (eg. CTLA-4, OX-40, CD137), and/or pazopanib Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of Investigational Product(IP). Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-Central Nervous System(CNS) disease. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, urothelial cancer, or carcinoma in situ that have undergone potentially curative therapy are not excluded. Has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable: without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention). Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Has a history of or current(non-infectious) pneumonitis/interstitial lung disease that required steroids Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are not required unless: Known history of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection As mandated by local health authority Known active infection requiring systemic therapy. Active infection including tuberculosis Active hepatitis B (HBsAg reactive and HBV DNA is detected) Active hepatitis C (anti-HCV reactive and HCV RNA [qualitative] is detected) Human immunodeficiency virus infection Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Has had an allogenic tissue/solid organ transplant. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    PP1

    PP2

    Arm Description

    pembrolizumab in combination with pazopanib

    pembrolizumab for patients progressing on pazopanib.

    Outcomes

    Primary Outcome Measures

    Progression Free Survival (PFS)
    Progression Free Survival (PFS)

    Secondary Outcome Measures

    Progression Free Rate (PFR)
    Progression Free Rate (PFR)
    Overall Response Rate (ORR)
    Overall Response Rate (ORR)
    Overall Survival(OS)
    Overall Survival(OS)
    Adverse Events(AE)
    Adverse Events(AE)

    Full Information

    First Posted
    December 26, 2022
    Last Updated
    July 18, 2023
    Sponsor
    Yonsei University
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05679921
    Brief Title
    Pazopanib With or Without Pembrolizumab for Metastatic Soft Tissue Sarcoma
    Official Title
    Pazopanib With or Without Pembrolizumab for Metastatic Soft Tissue Sarcoma: Open-label, Multicenter, Randomized, Phase 2 Trials
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 1, 2024 (Anticipated)
    Primary Completion Date
    December 31, 2026 (Anticipated)
    Study Completion Date
    December 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Yonsei University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    This is an open-label, randomized, phase II study to evaluate the clinical activity of pembrolizumab in combination with pazopanib compared to pazopanib monotherapy.
    Detailed Description
    Pembrolizumab will be given for a maximum of 2 years i.e. a total of 35 cycles of pembrolizumab with the q3 week dosing. Participants who complete study intervention after 2 years of pembrolizumab can be treated with pazopanib monotherapy based on physician's judgement. The duration of optional pembrolizumab crossover treatment will be maximum of 2 years i.e. a total of 35 cycles of pembrolizumab for patients progressing on pazopanib.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Soft Tissue Sarcoma
    Keywords
    Sarcoma, Pembrolizumab, Pazopanib

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    116 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    PP1
    Arm Type
    Experimental
    Arm Description
    pembrolizumab in combination with pazopanib
    Arm Title
    PP2
    Arm Type
    Experimental
    Arm Description
    pembrolizumab for patients progressing on pazopanib.
    Intervention Type
    Drug
    Intervention Name(s)
    pembrolizumab, pazopanib
    Intervention Description
    Pembrolizumab will be given for a maximum of 2 years i.e. a total of 35 cycles of pembrolizumab with the q3 week dosing. Participants who complete study intervention after 2 years of pembrolizumab can be treated with pazopanib monotherapy based on physician's judgement. The duration of optional pembrolizumab crossover treatment will be maximum of 2 years i.e. a total of 35 cycles of pembrolizumab for patients progressing on pazopanib.
    Primary Outcome Measure Information:
    Title
    Progression Free Survival (PFS)
    Description
    Progression Free Survival (PFS)
    Time Frame
    12 weeks
    Secondary Outcome Measure Information:
    Title
    Progression Free Rate (PFR)
    Description
    Progression Free Rate (PFR)
    Time Frame
    12 weeks
    Title
    Overall Response Rate (ORR)
    Description
    Overall Response Rate (ORR)
    Time Frame
    12 weeks
    Title
    Overall Survival(OS)
    Description
    Overall Survival(OS)
    Time Frame
    4 months
    Title
    Adverse Events(AE)
    Description
    Adverse Events(AE)
    Time Frame
    6 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically confirmed Soft Tissue Sarcoma(STS) progression to 1 or 2 (less than 3) prior chemotherapy : Exclude pazopanib-resistant subtype - embryonal rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing tumours, primitive neuroectodermal tumour, gastrointestinal stromal tumour, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma, and liposarcoma Age > 19 years at time of study entry. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 7 days before screening) Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 Adequate normal organ and marrow function as defined below Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥ 1500 per mm3 Platelet count ≥ 100,000 per mm3 Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). Aspartate Aminotransferase (AST, SGOT)/Alanine Aminotransferase (ALT, SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN Creatinine≤1.5 x ULN or Measured or calculated(CrCl should be calculated per institutional standard) creatinine clearance(GFR can also be used in place of creatinine or CrCl) ≥ 1.5 x institutional ULN International normalized ratio (INR) OR prothrombin time (PT) and activated partial thromboplastin time (aPTT) : ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. A male or female participant must agree to use a contraception as detailed in Appendix 2 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days after the last dose of study treatment. Archival tumor tissue sample or newly obtained [core, incisional or excisional] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Exclusion Criteria: Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug Any previous treatment with a Programmed Death-1(PD1) or Programmed Death-Ligand1(PD-L1) inhibitor, anti-PD-L2 agent, stimulatory/co-inhibitory T-cell receptor (eg. CTLA-4, OX-40, CD137), and/or pazopanib Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of Investigational Product(IP). Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-Central Nervous System(CNS) disease. Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, urothelial cancer, or carcinoma in situ that have undergone potentially curative therapy are not excluded. Has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable: without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention). Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Has a history of or current(non-infectious) pneumonitis/interstitial lung disease that required steroids Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are not required unless: Known history of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection As mandated by local health authority Known active infection requiring systemic therapy. Active infection including tuberculosis Active hepatitis B (HBsAg reactive and HBV DNA is detected) Active hepatitis C (anti-HCV reactive and HCV RNA [qualitative] is detected) Human immunodeficiency virus infection Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. Has had an allogenic tissue/solid organ transplant. Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Pazopanib With or Without Pembrolizumab for Metastatic Soft Tissue Sarcoma

    We'll reach out to this number within 24 hrs