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Safety and Efficacy Analysis of an Antibody Associated With a Chemotherapy for Patients With a Triple Negative Metastatic Breast Cancer (ISIdE)

Primary Purpose

Triple Negative Breast Cancer, Metastatic Breast Cancer

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Sacituzumab govitecan
Sponsored by
UNICANCER
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple Negative Breast Cancer focused on measuring breast cancer, metastatic, triple negative, sacituzumab govitecan, biomarker analysis

Eligibility Criteria

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

Inclusion Criteria:

  1. Patient must have signed a written informed consent prior to any trial specific procedures;
  2. Male or female โ‰ฅ18 years of age;
  3. Patients with pathologically documented locally advanced inoperable or metastatic triple negative breast cancer (mTNBC) whose disease has progressed either on 1st line chemotherapy with or without immune checkpoint inhibitors (ICIs) or target therapy (e.g. AKT inhibitor, PI3K inhibitor, PARP inhibitor) for metastatic or inoperable locally advanced breast cancer (ABC) or on (neo)adjuvant chemotherapy with or without immunotherapy for early TNBC or within 6 months after the end of any systemic therapy, surgery, or radiotherapy with curative intent, whatever comes last. The number of patients with early progression will be capped to 20% of the overall population;
  4. Prior exposure to a taxane in localized or advanced/metastatic setting;
  5. Measurable disease, as defined by RECIST v1.1
  6. Patient must have accepted to perform pre-treatment, on-treatment and post-treatment biopsies. If the physician considers doing the biopsy on the primary tumor site because accessibility, it can be performed only if the primary tumor site has not been previously irradiated;
  7. Have metastatic site easily accessible to biopsy (with exception of bone metastasis)
  8. Eastern Cooperative Oncology Group (ECOG) performance status โ‰ค2;
  9. Life expectancy โ‰ฅ12 weeks;
  10. Adequate haematologic and organ function
  11. Negative hepatitis B surface antigen (HBsAg) test at screening (patients with a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening are eligible), negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening;
  12. Evidence of post-menopausal status or negative pregnancy urinary test within 72 hours or serum pregnancy test within 14 days of study treatment and confirmed prior to treatment on Cycle 1 Day 1 (C1D1) for female pre-menopausal patients;
  13. Woman of childbearing potential and male patient must agree to use adequate contraception for the duration of trial participation and up to 6 months after completing treatment for women and up to 3 months for men;
  14. Patient affiliated to a social security system (or equivalent);
  15. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion Criteria:

  1. Participation in another therapeutic trial within the 30 days prior to enrolment;
  2. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases or evidence of leptomeningeal disease or clinically active spinal cord compression. Patients with stable and asymptomatic brain metastases will be eligible, yet the number will be capped to 15% of the overall population;
  3. Previous history of cancer other than mTNBC within 5 years prior to C1D1, except of those with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%) and treated with curative intent (e.g. carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer);
  4. Met any of the following criteria for cardiac disease:

    1. Myocardial infarction or unstable angina pectoris within 6 months of enrolment.
    2. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation.
    3. New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of <40%.
  5. Severe uncontrolled infection requiring oral or IV antibiotics within 4 weeks prior to C1D1;
  6. Major surgical procedure within 4 weeks prior to C1D1;
  7. History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized antibodies;
  8. Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
  9. Patients receiving concomitant anti-cancer treatments such as chemotherapy, immunotherapy, endocrine therapy and radiotherapy;
  10. Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved according to the common terminology criteria for adverse events of the National Cancer Institute (NCI-CTCAE) v5.0 grade >2
  11. Treatment with systemic corticosteroids dosed at >20 mg prednisone or equivalent or other systemic immunosuppressive medications within 2 weeks prior to C1D1;
  12. Known history of testing positive for HIV or known acquired immunodeficiency syndrome;
  13. Covid-19 infection at screening;
  14. Evidence of significant uncontrolled concomitant disease;
  15. Individuals with physical or psychological conditions considered not to be compatible with the trial;
  16. Persons deprived of their liberty or under protective custody or guardianship;
  17. Pregnant or breastfeeding women;
  18. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Single arm receiving sacituzumab govitecan

    Arm Description

    Outcomes

    Primary Outcome Measures

    Objective response rate (ORR)
    ORR is defined as the number of patient with at least a confirmed complete response (CR) or partial response (PR), based on the best objective response values while on treatment

    Secondary Outcome Measures

    Progression-free survival (PFS)
    PFS iis the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
    Duration of response (DOR)
    DOR is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of disease progression or death due to any cause
    Clinical benefice risk (CBR)
    CBR is defined as the presence of at least a PR or CR, or a stable disease (SD) while on treatment
    Overall Survival (OS)
    The overall survival is the length of time from randomization that patients enrolled in the study are still alive.
    The incidence of adverse events (Safety)
    Safety and tolerability of sacituzumab govitecan will be evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5). NCI-CTCAE is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.

    Full Information

    First Posted
    September 20, 2022
    Last Updated
    August 30, 2023
    Sponsor
    UNICANCER
    Collaborators
    Gilead Sciences
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05552001
    Brief Title
    Safety and Efficacy Analysis of an Antibody Associated With a Chemotherapy for Patients With a Triple Negative Metastatic Breast Cancer
    Acronym
    ISIdE
    Official Title
    ISIdE: Open Label, Multicentric, Single-arm Phase IIIB Trial to Evaluate the Safety and Efficacy of Sacituzumab Govitecan in Triple Negative Metastatic Breast Cancer Patients With a Biomarker Analysis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2023 (Anticipated)
    Primary Completion Date
    December 1, 2024 (Anticipated)
    Study Completion Date
    May 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    UNICANCER
    Collaborators
    Gilead Sciences

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    ISIdE is an European, multicentric study that aims to assess the efficacy of Sacituzumab Govitecan (SG) in locally advanced or metastatic triple-negative breast cancer where the disease has progressed despite chemotherapy or within 6 months after the end of curative treatments in order to: evaluate the treatment efficacy in less pretreated patients. identify biomarkers that could predict response or resistance to the drug. 100 patients will be included in this trial.
    Detailed Description
    ISIDE is a European, multicenter, open label, single-arm phase IIIB trial that aims to include 100 patients with pathologically documented locally advanced inoperable or metastatic triple negative breast cancer (mTNBC) whose disease has progressed either on: 1st line chemotherapy with or without immune checkpoint inhibitors (ICIs) or targeted therapy (e.g. AKT inhibitor, PI3K inhibitor, PARP inhibitor) for metastatic or inoperable locally advanced breast cancer (ABC) (neo)adjuvant chemotherapy with or without immunotherapy for early TNBC or within 6 months after the end of any systemic therapy, surgery or radiotherapy with curative intent, whatever comes last. The primary objective is to to evaluate the efficacy of sacituzumab govitecan via investigator-assessed objective response rate (ORR) according to RECIST v1.1. Patient will receive SG until disease progression, unacceptable toxicity, or decision to withdraw its participation.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Triple Negative Breast Cancer, Metastatic Breast Cancer
    Keywords
    breast cancer, metastatic, triple negative, sacituzumab govitecan, biomarker analysis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    96 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Single arm receiving sacituzumab govitecan
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Sacituzumab govitecan
    Other Intervention Name(s)
    trodelvy
    Intervention Description
    Sacituzumab Govitecan (SG) is given by intervenous route, 10 mg/kg on day 1 and day 8 of 21-day treatment cycles. Patient will receive treatment until disease progression, unacceptable toxicity, or decision to withdraw its participation.
    Primary Outcome Measure Information:
    Title
    Objective response rate (ORR)
    Description
    ORR is defined as the number of patient with at least a confirmed complete response (CR) or partial response (PR), based on the best objective response values while on treatment
    Time Frame
    From inclusion to disease progression, up to 6 months
    Secondary Outcome Measure Information:
    Title
    Progression-free survival (PFS)
    Description
    PFS iis the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
    Time Frame
    From inclusion to disease progression or death, up to 2 years
    Title
    Duration of response (DOR)
    Description
    DOR is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of disease progression or death due to any cause
    Time Frame
    From inclusion to disease progression or death, up to 2 years
    Title
    Clinical benefice risk (CBR)
    Description
    CBR is defined as the presence of at least a PR or CR, or a stable disease (SD) while on treatment
    Time Frame
    From inclusion to disease progression or death, up to 2 years
    Title
    Overall Survival (OS)
    Description
    The overall survival is the length of time from randomization that patients enrolled in the study are still alive.
    Time Frame
    From inclusion to disease progression or death, up to 2 years
    Title
    The incidence of adverse events (Safety)
    Description
    Safety and tolerability of sacituzumab govitecan will be evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5). NCI-CTCAE is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.
    Time Frame
    Throughout study completion, up to 36 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patient must have signed a written informed consent prior to any trial specific procedures; Note; When the patient is unable to write to give his written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent Male or female โ‰ฅ 18 years of age; Patients with pathologically documented locally advanced inoperable or metastatic triple negative breast cancer (mTNBC) whose disease has progressed either on 1st line chemotherapy +/- immune checkpoint inhibitors (ICIs) or target therapy (e.g. AKT inhibitor, PI3K inhibitor, PARP inhibitor) for metastatic or inoperable locally advanced breast cancer (ABC) or on (neo)adjuvant chemotherapy+/-immunotherapy for early TNBC or within 6 months after the end of any systemic therapy, surgery or radiotherapy with curative intent, whatever comes last. Note: TNBC is defined as the absence of HER2 overexpression by immunohistochemistry (IHC) defined as IHC 0, 1+, or 2+ and fluorescence in situ hybridization [FISH] non-amplified and estrogen receptor (ER) expression <10% and progesterone receptor (PR) expression <10% by local pathological assessment on the baseline biopsy or in a recent tissue sample collected within 1 month Prior exposure to a taxane in localized or advanced/metastatic setting; If indicated, prior therapy with ICI for patients with PD1 positive tumor and prior treatment with PARP inhibitor for patients with gBRCAm Measurable disease, as defined by RECIST v1.1 Patient must have accepted to perform pre-treatment, on-treatment and post-treatment biopsies. If the physician considers doing the biopsy on the primary tumor site because accessibility, it can be performed only if the primary tumor site has not been previously irradiated; Have metastatic site easily accessible to biopsy (with exception of bone metastasis) Note: Patients with only bone metastasis will be eligible if the primary tumor is accessible for biopsy at inclusion Eastern Cooperative Oncology Group (ECOG) performance status โ‰ค2; Life expectancy โ‰ฅ12 weeks; Adequate haematologic and organ function Negative hepatitis B surface antigen (HBsAg) test at screening (patients with a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening are eligible), negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening; Evidence of post-menopausal status or negative pregnancy urinary test within 72 hours or serum pregnancy test within 14 days before study treatment and confirmed prior to treatment on Cycle 1 Day 1 for female pre-menopausal patients; Woman of childbearing potential and male patient must agree to use adequate contraception for the duration of trial participation and up to 6 months after completing treatment for women and up to 3 months for men; Patient affiliated to a social security system (or equivalent); Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up; Exclusion Criteria: Participation in another therapeutic trial within the 30 days prior to enrolment; Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases or evidence of leptomeningeal disease or clinically active spinal cord compression. Patients with stable and asymptomatic brain metastases will be eligible, yet the number will be capped to 15% of the overall population; Previous history of cancer other than mTNBC within 5 years prior to C1D1, except of those with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%) and treated with curative intent (e.g. carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer); Met any of the following criteria for cardiac disease: Myocardial infarction or unstable angina pectoris within 6 months of enrolment. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of <40%. Severe uncontrolled infection requiring oral or IV antibiotics within 4 weeks prior to C1D1; Major surgical procedure within 4 weeks prior to C1D1; History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized antibodies; Known hypersensitivity to the study drug, its metabolites, or formulation excipient. Patients receiving concomitant anti-cancer treatments such as chemotherapy, immunotherapy, endocrine therapy and radiotherapy; Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved according to the common terminology criteria for adverse events of the National Cancer Institute (NCI-CTCAE) v5.0 grade >2 Treatment with systemic corticosteroids dosed at >20 mg prednisone or equivalent or other systemic immunosuppressive medications within 2 weeks prior to C1D1; Known history of testing positive for HIV or known acquired immunodeficiency syndrome; Covid-19 infection at screening; Evidence of significant uncontrolled concomitant disease; Individuals with physical or psychological conditions considered not to be compatible with the trial; Persons deprived of their liberty or under protective custody or guardianship; Pregnant or breastfeeding women; Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Clara GUYONNEAU, PharmD
    Phone
    0685167111
    Ext
    +33
    Email
    c-guyonneau@unicancer.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Barbara Pistilli, MD
    Organizational Affiliation
    Gustave Roussy, Cancer Campus, Grand Paris
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Safety and Efficacy Analysis of an Antibody Associated With a Chemotherapy for Patients With a Triple Negative Metastatic Breast Cancer

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