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Pembrolizumab Plus Lenvatinib in Previously Treated Classic Kaposi Sarcoma (PULSAR)

Primary Purpose

Kaposi Sarcoma, Classic Kaposi Sarcoma, Refractory Kaposi Sarcoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pembrolizumab + Lenvatinib
Sponsored by
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kaposi Sarcoma

Eligibility Criteria

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

Inclusion Criteria: Have a histologically confirmed diagnosis of classic (or endemic) KS Progression or inadequate response to at least one prior systemic chemotherapy Presence of measurable disease by PET-CT scan and/or dermatological examination KS with at least 10 cutaneous and/or mucosal lesions, or involving more than one limb segment or with involvement >3% body surface KS with at least 4 lesions ≥ 5mm KS with at least 1 superficial lesion willing to provide tissue from cutaneous and/or mucosal biopsy at baseline At least 4 weeks washout for all KS specific therapies including chemotherapy (both systemic and intralesional) and radiotherapy Be ≥ 18 years of age at the time of signing informed consent Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization. Exclusion Criteria: Has a known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies detected at screening). Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. 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. Patients with vitiligo, type I diabetes mellitus, hypothyroidism, psoriasis not requiring systemic treatment are permitted to enroll. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Single Arm

    Arm Description

    Outcomes

    Primary Outcome Measures

    Overall Response Rate (ORR) of pembrolizumab with lenvatinib in pre-treated recurrent CKS
    the combination of pembrolizumab and lenvatinib has superior ORR, as compared to cytotoxic chemotherapy by literature data. ORR defined as a confirmed complete response (CR) or partial response (PR).

    Secondary Outcome Measures

    Duration of response (DOR) in patients with pre-treated recurrent CKS receiving pembrolizumab with lenvatinib
    The combination of pembrolizumab and lenvatinib provides superior DOR, as compared to cytotoxic chemotherapy by literature data.
    Progression Free Survival (PFS) of patients with pre-treated recurrent CKS receiving pembrolizumab with lenvatinib.
    The combination of pembrolizumab and lenvatinib has superior PFS, as compared to cytotoxic chemotherapy by literature data.
    Overall Survival in patients receiving pembrolizumab and lenvatinib
    The combination of pembrolizumab and lenvatinib has superior OS, as compared to cytotoxic chemotherapy by literature data.
    The mean change from baseline in the global health status/quality of life (QoL), and physical functioning for the combinations of pembrolizumab and lenvatinib
    Score for the following patient-reported outcomes (PROs) scales/items: global health status/QoL (EORTC QLQ-C30items 29 and 30), and physical functioning (EORTC QLQ-C30 items 1-5).
    Safety and tolerability for the combination of pembrolizumab and lenvatinib.
    Adverse Events (AEs) incidence and study intervention discontinuation due to AEs

    Full Information

    First Posted
    April 27, 2023
    Last Updated
    May 8, 2023
    Sponsor
    Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05846724
    Brief Title
    Pembrolizumab Plus Lenvatinib in Previously Treated Classic Kaposi Sarcoma
    Acronym
    PULSAR
    Official Title
    A Phase II Single-arm Study of Pembrolizumab Plus Lenvatinib in Previously Treated Classic Kaposi Sarcoma (CKS)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 1, 2023 (Anticipated)
    Primary Completion Date
    March 1, 2028 (Anticipated)
    Study Completion Date
    March 1, 2029 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    Brief Summary
    Phase II study of Pembrolizumab plus Lenvatinib in relapsed/refractory Classic Kaposi Sarcoma (CKS). After a screening phase of up to 28 days, each participant will receive study intervention of pembrolizumab plus lenvatinib until reaching a discontinuation criterion: disease progression; unacceptable adverse event(s) (AEs); intercurrent illness that prevents further administration of treatment; participant withdraws consent; pregnancy of participant; non-compliance with study intervention or procedure requirements; or administrative reasons requiring cessation of treatment. After the end of treatment, each participant will be followed for the occurrence of AEs and spontaneously reported pregnancy. Participants who discontinue for reasons other than PD will have post-treatment follow-up for disease status until PD is documented clinically by a team of committed dermatologists, and/or radiographically per RECIST 1.1, a non-study anticancer treatment is initiated, consent is withdrawn, or the participant becomes lost to follow-up. All participants will be followed for overall survival (OS) until death, withdrawal of consent,lost to follow-up, or the end of the study. The end of the study will be when the last participant completes the last study-related telephone call or visit,withdraws from the study, or is lost to follow-up.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Kaposi Sarcoma, Classic Kaposi Sarcoma, Refractory Kaposi Sarcoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    25 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Single Arm
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Pembrolizumab + Lenvatinib
    Intervention Description
    single-arm study of pembrolizumab plus lenvatinib
    Primary Outcome Measure Information:
    Title
    Overall Response Rate (ORR) of pembrolizumab with lenvatinib in pre-treated recurrent CKS
    Description
    the combination of pembrolizumab and lenvatinib has superior ORR, as compared to cytotoxic chemotherapy by literature data. ORR defined as a confirmed complete response (CR) or partial response (PR).
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    Duration of response (DOR) in patients with pre-treated recurrent CKS receiving pembrolizumab with lenvatinib
    Description
    The combination of pembrolizumab and lenvatinib provides superior DOR, as compared to cytotoxic chemotherapy by literature data.
    Time Frame
    6 months
    Title
    Progression Free Survival (PFS) of patients with pre-treated recurrent CKS receiving pembrolizumab with lenvatinib.
    Description
    The combination of pembrolizumab and lenvatinib has superior PFS, as compared to cytotoxic chemotherapy by literature data.
    Time Frame
    6 months
    Title
    Overall Survival in patients receiving pembrolizumab and lenvatinib
    Description
    The combination of pembrolizumab and lenvatinib has superior OS, as compared to cytotoxic chemotherapy by literature data.
    Time Frame
    6 months
    Title
    The mean change from baseline in the global health status/quality of life (QoL), and physical functioning for the combinations of pembrolizumab and lenvatinib
    Description
    Score for the following patient-reported outcomes (PROs) scales/items: global health status/QoL (EORTC QLQ-C30items 29 and 30), and physical functioning (EORTC QLQ-C30 items 1-5).
    Time Frame
    6 months
    Title
    Safety and tolerability for the combination of pembrolizumab and lenvatinib.
    Description
    Adverse Events (AEs) incidence and study intervention discontinuation due to AEs
    Time Frame
    6 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Have a histologically confirmed diagnosis of classic (or endemic) KS Progression or inadequate response to at least one prior systemic chemotherapy Presence of measurable disease by PET-CT scan and/or dermatological examination KS with at least 10 cutaneous and/or mucosal lesions, or involving more than one limb segment or with involvement >3% body surface KS with at least 4 lesions ≥ 5mm KS with at least 1 superficial lesion willing to provide tissue from cutaneous and/or mucosal biopsy at baseline At least 4 weeks washout for all KS specific therapies including chemotherapy (both systemic and intralesional) and radiotherapy Be ≥ 18 years of age at the time of signing informed consent Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 Have adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization. Exclusion Criteria: Has a known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies detected at screening). Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. 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. Patients with vitiligo, type I diabetes mellitus, hypothyroidism, psoriasis not requiring systemic treatment are permitted to enroll. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137). 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.

    12. IPD Sharing Statement

    Learn more about this trial

    Pembrolizumab Plus Lenvatinib in Previously Treated Classic Kaposi Sarcoma

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