Substantially improving the cure rate of high-risk BRCA1-like breast cancer patients with personalized therapy (SUBITO) an international randomized phase III trial

Substantially improving the cure rate of high-risk BRCA1-like breast cancer patients with personalized therapy (SUBITO) an international randomized phase III trial - SUBITO

Status

Recruiting

Phases

Phase 3

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON56057

Enrollment

Registered

2016-09-15

Start date

2017-01-25

Completion date

Unknown

Last updated

2025-08-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

breast cancer

Interventions

Both study arms: 3 x ddAC q 2 weeks doxorubicin 60 mg/m² as an i.v. bolus and cyclophosphamide 600 mg/m² as an i.v. bolus on day 1 every 2 weeks ddAC must be supported with prophylactic pegfilgrastim

(or AUC=5 in patients with a calculated creatinine-clearance of <100 ml/min)) days 1,2 thiotepa 250 mg/m2 day 2 AC-CP-olaparib: Patients will receive a 4th cycle of ddAC, followed by carboplatin/pac

Eligibility

Age

18 Years to 64 Years

Inclusion criteria

Inclusion criteria: - Women and men with stage III adenocarcinoma of the breast harboring signs of a breast cancer with features of homologous recombination deficiency (HRD) - Age of 18-65 years - The tumor must be HER2-negative - Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Exclusion criteria

Exclusion criteria: - Distant metastases - Previous radiation therapy - Previous chemotherapy - Any previous treatment with a PARP-inhibitor, including olaparib - Pre-existing neuropathy from any cause in excess of Grade 1 - Chronic concomitant use of known strong or moderate CYP3A inducers

Design outcomes

Primary

Measure	Time frame
Primary endpoint is overall survival defined as the time from randomization to death from any cause.in all patients	—

Secondary

Measure	Time frame
Key secondary endpoint: Overall survival, defined as the time from randomization to death from any cause in patients without a germline BRCA1/2 mutation. Other Secondary endpoints: A - 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 B - recurrence-free interval defined as time from randomization to invasive ipsilateral breast tumor recurrence, locoregional- or distant recurrence, or death from breast cancer[27], 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). C - (non-)hematological toxicity determined according to CTCAE v4.03 D - cost-effectiveness measured by costs per quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). E - Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires F - several potential biomarkers, e.g.: cell-free circulating tumor DNA tumor educated platelets RNA cancer immune interaction and reconstitution XIST expression by primary tumor 53BP1 tumor expression of primary tumor Functional ex-vivo RAD51 assay Circulating tumor cells in peripheral blood stem cell (PBSC) harvest G - 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)).	—

Measure

Time frame

Key secondary endpoint: Overall survival, defined as the time from randomization to death from any cause in patients without a germline BRCA1/2 mutation. Other Secondary endpoints: A - 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 B - recurrence-free interval defined as time from randomization to invasive ipsilateral breast tumor recurrence, locoregional- or distant recurrence, or death from breast cancer[27], 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). C - (non-)hematological toxicity determined according to CTCAE v4.03 D - cost-effectiveness measured by costs per quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). E - Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires F - several potential biomarkers, e.g.: cell-free circulating tumor DNA tumor educated platelets RNA cancer immune interaction and reconstitution XIST expression by primary tumor 53BP1 tumor expression of primary tumor Functional ex-vivo RAD51 assay Circulating tumor cells in peripheral blood stem cell (PBSC) harvest G - 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)).

—

Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)