Inositol trispyrophosphate hexasodium for Metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- Women or men aged more than or equal to 18 years old"}
• {"criterion_text":"- Initial serum calcium and fasting blood glucose levels must be normal"}
• {"criterion_text":"- Metastatic setting of a histologically confirmed adenocarcinoma of the breast"}
• {"criterion_text":"- Overexpression of HER2 in the primary tumor or a metastatic lesion (3+ by ICH or 2+ with confirmation of positivity by FISH or SISH)"}
• {"criterion_text":"- Performance status = 0, 1 or 2"}
• {"criterion_text":"- Metastatic disease requiring the initiation of an anti HER2 containing regimen"}
• {"criterion_text":"- First line treatment for metastatic disease"}
• {"criterion_text":"- Patients for whom a minimum of 3-month life expectancy is anticipated"}
• {"criterion_text":"- Baseline LVEF value > 50%, measured by cardiac MRI, by echocardiography (Simpson’s method) or by MUGA scan within 7 days before randomization. According to trastuzumab and pertuzumab Summary of Product Characteristics"}
• {"criterion_text":"- Informed consent form signed"}

Exclusion criteria

• {"criterion_text":"- Patients not eligible for anti-HER2 therapy"}
• {"criterion_text":"- People with diabetes"}
• {"criterion_text":"- Persons deprived of liberty by judicial or administrative decision"}
• {"criterion_text":"- Persons not affiliated to a social security system or equivalent"}
• {"criterion_text":"- Persons receiving psychiatric medical care"}
• {"criterion_text":"- Persons subject to a legal protection measure (guardianship, curatorship, safeguard of justice)"}
• {"criterion_text":"- Patients previously treated at the metastatic setting by systemic treatment"}
• {"criterion_text":"- Serious cardiac illness or medical conditions disallowing administration of anti-HER2 therapy. According to trastuzumab and pertuzumab SPCs"}
• {"criterion_text":"- Known hypersensitivity to trastuzumab, pertuzumab, TherO2-01S22, murine proteins or to any of the excipients"}
• {"criterion_text":"- Spinal cord compression and/or symptomatic or progressive brain metastases (Brain metastasis are not acceptable unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug)."}
• {"criterion_text":"- Patients who, for social, geographic or psychological reasons, cannot be adequately followed up and/or are incapable of undergoing regular controls"}
• {"criterion_text":"- Pregnant or breastfeeding women"}

Primary endpoints

• {"endpoint_text":"- Objective response rate (ORR): Percentage of patients whose disease decreased (Partial Response, PR) and / or disappears (Complete Response, CR) after treatment, according to RECIST V1.1 criteria20 and according to the adapted EORTC criteria for 18F-FDG PET-scan : Time Frame: at D43","definition_or_measurement_approach":"Percentage of patients whose disease decreased (Partial Response, PR) and / or disappears (Complete Response, CR) after treatment, according to RECIST V1.1 criteria and according to the adapted EORTC criteria for 18F-FDG PET-scan. Time Frame: at D43."}

Secondary endpoints

• {"endpoint_text":"- Progression-Free Survival (PFS): defined as the time interval from the date of randomization to the date of progression. Events considered as progression include local or distant progression, appearance of a second cancer or death (all causes) whichever occurs first. Time Frame: every 3 months up to 24 months from randomization","definition_or_measurement_approach":"PFS defined as time from randomization to date of progression (local/distant), appearance of second cancer, or death, whichever occurs first. Tumor assessments every 3 months up to 24 months."}
• {"endpoint_text":"- Overall Survival (OS): defined as the time interval from the date of randomization to the date of death, regardless of disease progression. Time Frame: every 3 months up to 24 months from randomization","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause. Follow-up every 3 months up to 24 months."}
• {"endpoint_text":"- Safety: Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs) classified according to the CTCAE v5.0 criteria. Record of all AEs (regardless of imputability) until the safety visit. Time Frame: from randomization to D64","definition_or_measurement_approach":"Incidence of AEs and SAEs per CTCAE v5.0. Record all AEs from randomization to D64; treatment-related AEs collected up to 24 months."}
• {"endpoint_text":"- Cardiotoxicity: defined by decrease in Left Ventricular Ejection Fraction (LVEF) value according to the modality performed (cardiac MRI, MUGA scan or echocardiography) and any other cardiac toxicities revealed by physical examination or any other adequate exam (CTCAE v5.0 criteria). Time Frame: every 3 months up to 24 months from randomization","definition_or_measurement_approach":"Cardiotoxicity defined by decrease in LVEF measured by MRI, MUGA or echocardiography and other cardiac toxicities per CTCAE v5.0. Assessments every 3 months up to 24 months."}
• {"endpoint_text":"- Quality of life: QLQ-C30 and BR23 auto-questionnaire Time Frame: at baseline and D43","definition_or_measurement_approach":"Quality of life measured by EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and D43."}
• {"endpoint_text":"- Summary of oral TherO2-01S22 pharmacokinetics parameters. PK samples to be collected before IMP or placebo intake, and at 15, 30, 45, 60, 120, 240, 300 min after the intake as detailed in section 10.1. Time Frame: at D-1 of cycle 1 and cycle 2","definition_or_measurement_approach":"PK sampling before intake and at 15, 30, 45, 60, 120, 240, 300 minutes post-dose. Time points at D-1 of cycle 1 and D-1 of cycle 2."}
• {"endpoint_text":"- Summary of trastuzumab/pertuzumab pharmacokinetics parameters. PK samples to be collected prior to trastuzumab/pertuzumab administration as detailed in section 10.2. Time Frame: at D1 of cycle 2 and at D43 (corresponding to the day 1 of cycle 3 of trastuzumab/pertuzumab","definition_or_measurement_approach":"PK samples collected prior to trastuzumab/pertuzumab administration. Time Frame: D1 of cycle 2 and D43 (day 1 of cycle 3 of trastuzumab/pertuzumab)."}

France

Earliest CTIS Part Ii Submission Date

18-09-2025

Latest Decision Or Authorization Date

02-12-2025

Processing Time Days

75

Number Of Sites

3

Number Of Participants

224

Primary sponsor

Full Name

Centre Regional Lutte Contre Le Cancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France