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.
- Trial ID
- 2022-502369-10-00
- Protocol
- UC-BCG-2204
- Sponsor
- Unicancer
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of sacituzumab govitecan in patients with triple negative metastatic breast cancer (mTNBC) or inoperable locally advanced breast cancer (ABC). This will be assessed through the investigator-assessed objective response rate (ORR) according to RECIST v1.1 criteria. The clinical relevance of this objective lies in determining the potential of sacituzumab govitecan to provide a therapeutic benefit in a population with limited treatment options, particularly those whose disease has progressed following (neo)adjuvant chemotherapy for early TNBC or within six months after the completion of curative treatments.
Secondary objectives include:
- **Efficacy**: To evaluate progression-free survival (PFS), duration of response (DOR), clinical benefit rate (CBR), and overall survival (OS). Additionally, the study will analyze these efficacy endpoints in subgroups defined by previous treatment lines.
- **Safety**: To assess the safety profile of sacituzumab govitecan in the overall population and specifically in patients homozygous for the UGT1A1*28 allele and other polymorphisms affecting UGT1A1 expression.
- **Exploratory**: To describe TROP-2 expression levels and gene-expression profiling during treatment, identify biomarkers associated with treatment response or resistance, assess the modulation of circulating tumor cells (CTCs) by sacituzumab govitecan, and explore immune effects associated with the treatment.
Participants
The clinical trial involves participants diagnosed with **triple negative metastatic breast cancer** (mTNBC) or inoperable locally advanced breast cancer (ABC). The study population includes both male and female subjects aged 18 years and older. Participants are required to have a life expectancy of at least 12 weeks and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. The trial population was selected based on the progression of their disease following (neo)adjuvant chemotherapy for early TNBC or within six months after the completion of curative treatments. Participants must have adequate hematologic and organ function, and they should not have active hepatitis B or C infections. The trial includes individuals who are post-menopausal or have a negative pregnancy test, and both male and female participants must agree to use adequate contraception during the trial and for a specified period after treatment. The sponsor has not provided information regarding the total number of participants. The study considers lifestyle factors such as the ability to comply with the protocol, including treatment, scheduled visits, and follow-up examinations. Participants must be affiliated with a social security system or equivalent. The trial does not specify any particular dietary or physical activity requirements.
Plans and Procedures
The clinical trial is designed as an open-label, multicentric, single-arm phase IIIB study to evaluate the safety and efficacy of **sacituzumab govitecan** in patients with **triple negative metastatic breast cancer**. The primary objective is to assess the anti-tumor activity of sacituzumab govitecan, measured by the objective response rate (ORR) based on investigator assessment, using RECIST v1.1 criteria. The trial is expected to commence recruitment on January 2, 2023, and conclude by January 2, 2026. Participants will receive the investigational medicinal product, Trodelvy, administered as a solution for infusion via intravenous perfusion.
The trial involves a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as adequate hematologic and organ function, negative hepatitis tests, and measurable disease. Following the screening, participants will undergo treatment cycles with regular follow-up visits every six weeks to monitor treatment response and safety. These visits will include radiological assessments to evaluate disease progression. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
Participant involvement is anticipated to last up to three months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent. The trial will also explore secondary endpoints such as progression-free survival (PFS), duration of response (DOR), and overall survival (OS), alongside safety assessments and exploratory endpoints related to genomic alterations and immune response.
Treatment
The clinical trial involves the administration of **Trodelvy**, a pharmaceutical product containing the active substance **sacituzumab govitecan**. Trodelvy is formulated as a **powder for concentrate for solution for infusion** and is intended for **intravenous perfusion use**. The active substance, sacituzumab govitecan, is a **Trop-2-directed antibody-drug conjugate** and is classified as a humanized monoclonal antibody. The maximum daily dose is 10 mg/kg, with a total maximum dose of 10 mg/kg, administered over a treatment period of up to 3 weeks. The product is manufactured by Gilead Sciences Ireland UC and is not a pediatric formulation.
In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the efficacy and safety of sacituzumab govitecan in patients with triple-negative metastatic breast cancer. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.
Efficacy
The efficacy of **sacituzumab govitecan** in the clinical trial will be assessed primarily through the objective response rate (ORR), as evaluated by investigators using RECIST v1.1 criteria. ORR is defined as the proportion of patients achieving a confirmed complete response (CR) or partial response (PR) without the initiation of new anticancer therapy. Radiological assessments to determine treatment response will be conducted every six weeks.
Secondary efficacy endpoints include progression-free survival (PFS), duration of response (DOR), clinical benefit rate (CBR), and overall survival (OS). PFS is measured from the first dose to the first documentation of disease progression or death. DOR is the time from the first documentation of CR or PR to the first documentation of progression or death. CBR includes patients with at least a PR, CR, or stable disease without starting new anticancer therapy. OS is defined as the time from the first dose until death, with patients alive at last follow-up being censored at that date.
Exploratory endpoints involve the evaluation of TROP-2 dynamics, genomic alterations through whole exome sequencing, circulating tumor cells (CTCs) levels, and the impact of sacituzumab govitecan on immune cells. These assessments will be conducted using biopsies and samples collected at baseline, during treatment, and upon progression.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient must have signed a written informed consent prior to any trial specific procedures; Note; When the patient is physically unable to give their 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 ≥ 18 years of age;
- Patients with pathologically documented locally advanced inoperable or metastatic triple negative breast cancer (mTNBC) whose disease has progressed 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.
- Prior exposure to a taxane in localized or advanced/metastatic setting; Note: If indicated, prior therapy with ICI for patients with PD1 positive tumor and prior treatment with PARP inhibitor for patients with gBRCAm is required
- Measurable disease, as defined by RECIST v1.1
- Patient must have accepted to perform on-treatment biopsie. 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 1 : Patients with only bone metastasis will be eligible if the primary tumor is accessible for on treatment biopsy. Note 2 : If the patient has a single measurable lesion and it is the only one that can be biopsied, the patient cannot be included because the disease is no longer measurable according to RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
- Life expectancy ≥12 weeks;
- Adequate haematologic and organ function: Hematologic counts : Hemoglobin ≥9 g/dL, Absolute neutrophil count ≥1500/mm3 or ≥1.5 x 109/L Platelets ≥100,000/μL (without transfusional or growth factor support within 2 weeks of study drug initiation) Serum creatinine (SCr) ; Creatinine clearance (CrCl) ≥30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl; Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) : AST and ALT ≤ 2.5 ULN or ≤ 5 ULN if known liver metastases; Total bilirubin : ≤1.5 × upper limit of normal (ULN) if no liver metastases (<3 × ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline); Serum albumin : >3 g/dL
- 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 of 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 C1D1;
- 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;
- Known 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.
- 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: a) Myocardial infarction or unstable angina pectoris within 6 months of enrolment. b) 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. c) 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;
- Prior treatment with topoisomerase-1 inhibitor or with ADC containing topoisomerase-1 inhibitor
- Requirement for ongoing therapy with medications that are prohibited or to be used with caution
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 02 Jan 2023 | 10 |
 France | Not Recruiting | 02 Jan 2023 | 38 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Trodelvy 200 mg powder for concentrate for solution for infusion. | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS PERFUSION USE | 10 | 3 | PRD9351384 |