PACLITAXEL for Breast cancer | Stage III breast cancer

Inclusion criteria

• {"criterion_text":"- Males or females ≥18 and <66 years of age and fit to undergo autologous stem cell transplantation\n- Histologically confirmed adenocarcinoma of the breast\n- The tumor must be: HER2-negative (either score 0 or 1 at immunohistochemistry or negative at in situ hybridization [CISH or FISH] in case of score 2 at immunohistochemistry);AND Hormone receptor negative; or in case of a histological grade III tumor an estrogen receptor of <50% and progesterone receptor of <50% (Unless BRCA1 or BRCA2 germline mutation carrier)\n- Patients treated in the neoadjuvant setting\n- Women and men with stage III adenocarcinoma of the breast (according to AJCC staging manual 7th edition; Stage IIIA: T0-2N2 or T3N1-2; Stage IIIB: T4N0-2; Stage IIIC: any TN3) harboring signs of a breast cancer with features of homologous recombination deficiency (HRD) Based on the results of the preliminary work, the following HRD working definition will be employed: The patient is a known BRCA1 or BRCA2 mutation carrier; and/or the tumor exhibits a BRCA1 promoter hypermethylation, and/or the tumor exhibits a BRCA1-like DNA copy number profile\n- Eastern Cooperative Oncology Group (ECOG) performance status 0-1\n- Provision of informed consent"}

Exclusion criteria

• {"criterion_text":"- Evidence of distant metastases\n- Previous radiation therapy\n- Previous chemotherapy (except for ddAC cycles 1-3 for the current breast cancer, or another third generation chemotherapy cycle 1\n- Any previous treatment with a PARP-inhibitor, including olaparib\n- Pre-existing neuropathy from any cause > Grade 1\n- Pregnant; or breastfeeding and not willing to stop breastfeeding in order to be able to participate in the study"}

Primary endpoints

• {"endpoint_text":"- Overall survival, defined as the time from randomization to death from any cause in all patients.","definition_or_measurement_approach":"Defined as the time from randomization to death from any cause in all patients."}

Secondary endpoints

• {"endpoint_text":"- Key secondary endpoint: Overall survival, defined as the time from randomization to death from any cause in patients without a germline BRCA1/2 mutation.","definition_or_measurement_approach":"Defined as the time from randomization to death from any cause in patients without a germline BRCA1/2 mutation."}
• {"endpoint_text":"- Recurrence-free interval, defined as time from randomization to invasive ipsilateral breast tumor recurrence, locoregional- or distant recurrence, or death from breast cancer, whichever comes first, in all patients, regardless of germline BRCA1/2 status.","definition_or_measurement_approach":"Defined as time from randomization to invasive ipsilateral breast tumor recurrence, locoregional- or distant recurrence, or death from breast cancer, whichever comes first, in all patients."}
• {"endpoint_text":"- Recurrence-free interval defined as time from randomization to invasive ipsilateral breast tumor recurrence, locoregional- or distant recurrence, or death from breast cancer, whichever comes first, in patients with an HR impaired tumor (i.e. harboring a BRCA1-like copy number profile or BRCA1 promotor hypermethylation, in the absence of a known germline BRCA1/2 mutation).","definition_or_measurement_approach":"Defined as time from randomization to invasive ipsilateral breast tumor recurrence, locoregional- or distant recurrence, or death from breast cancer, whichever comes first, in the specified HR-impaired subgroup."}
• {"endpoint_text":"- (non-)hematological toxicity determined according to CTCAE v4.03.","definition_or_measurement_approach":"Toxicity graded and determined according to CTCAE v4.03."}
• {"endpoint_text":"- cost-effectiveness measured by costs per quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER).","definition_or_measurement_approach":"Cost-effectiveness assessed by costs per QALYs and incremental cost-effectiveness ratio (ICER)."}
• {"endpoint_text":"- Patient reported outcomes; including an interview, quality of life (QoL) determined by a comprehensive panel of QoL questionnaires and cognitive function","definition_or_measurement_approach":"Patient-reported outcomes collected via interviews and a comprehensive panel of QoL questionnaires; cognitive function assessments are included."}
• {"endpoint_text":"- Several potential biomarkers","definition_or_measurement_approach":"Biomarker analyses (potential biomarkers) planned; no further measurement detail provided in CTIS record."}
• {"endpoint_text":"- The difference in overall survival between patients treated in the SUBITO trial and patients with the same characteristics treated outside of the trial in the Netherlands (using data from the Netherlands Cancer Registry (NCR)).","definition_or_measurement_approach":"Comparative analysis of overall survival using trial data versus external patient data from the Netherlands Cancer Registry (NCR)."}

Netherlands

Earliest CTIS Part Ii Submission Date

21-01-2025

Latest Decision Or Authorization Date

23-01-2025

Processing Time Days

2

Number Of Sites

9

Number Of Participants

170

France

Earliest CTIS Part Ii Submission Date

21-01-2025

Latest Decision Or Authorization Date

29-01-2025

Processing Time Days

8

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"KWF Dutch Cancer Society","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"ZonMw","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"AstraZeneca/ Daiichi Sankyo","duties_or_roles":"Monetary support","organisation_type":""}