Biomarkers of Efficacy and Tolerability of Sacituzumab-Govitecan in the Treatment of Patients With Triple-negative Breast Cancer in the Metastatic Phase: Prospective Multicenter Real-world Study (BIO-PROSA)

Observational, prospective, multicenter study. Collection of data relating to the effectiveness of sacituzumab govitecan SG, in a real-world context and planned research of predictive biomarkers of efficacy/tolerability carried out on multiple platforms at the center coordinator.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: data collection

Detailed Description

Identification and inclusion in the study of patients affected by metastatic triple-negative breast cancer mTNBC, treated with sacituzumab govitecan SG as indicated at the participating centers.

Histological and biomolecular characteristics will be evaluated both on the tumor at diagnosis and on tissue resulting from biopsy of the metastatic site, where available. Otherwise, the analyzes will come anyway carried out on the most recent and available tumor tissue, whether deriving from primary tumor or site metastatic.

The search for biomarkers predictive of efficacy/tolerability will be carried out on tumor tissue (where possible both primary and metastatic) and on circulating plasma collected at two separate time points (T0 and T1).

Biomolecular characterization on the biological material of the enrolled patients (tumor tissue and plasma) will be carried out at the end of the study.

The feasibility of organoid development and single-cell sequencing will be evaluated on a small subgroup of patients, among those enrolled at the coordinating center, considering the need for tumor tissue prepared fresh for both methods.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Patrizia Vici, Doctor; Phone Number: +39 06-5266.5584; Email: patrizia.vici@ifo.it
• Study Contact Backup: Name: Eriseld Krasniqi, Doctor; Email: eriseld.krasniqi@ifo.it

Study Locations

• Italy
  • Rome, Italy, 00144
    • Recruiting
    • "Regina Elena" National Cancer Institute
    • Contact: Patrizia Vici, Doctor; Phone Number: +39 06-5266.5584; Email: patrizia.vici@ifo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with metastatic triple-negative breast cancer treated with socituzumab govitecan as indicated, with at least one sample of tumor tissue available.

Description

Inclusion Criteria:

• Age ≥ 18 years;
• Histological diagnosis of TNBC;
• Locally advanced unresectable or metastatic disease;
• Indication for treatment with SG in monotherapy according to clinical practice (patients pre-treated with at least two lines of systemic therapy, of which at least one in an advanced stage);
• Availability of at least one tumor tissue sample (from primary tumor or metastasis) to be sent to the coordinating center (IRE);
• Written informed consent;
• Availability to comply with the procedures established by the protocol, according to the methods and times described.

Exclusion Criteria:

• Patients with a history of other malignancies;
• Contraindications to the use of sacituzumab govitecan SG;
• Untreated and/or clinically unstable (symptomatic) brain metastases.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

patients with metastatic triple-negative breast cancer treated with sacituzumab govitecan; The availability of at least one tumor tissue sample to be transferred to the coordinating center will be essential for enrollment in the study. For patients for whom a new sampling is scheduled biopsy of the tumor (primary or metastasis) as per clinical practice, the feasibility of the development will be assessed tumor organoids and the execution of single-cell sequencing on tumor tissue. In these cases, the order of priority in dividing the sampled tissue will be: sufficient quota to carry out the histological examination that will have to be carried out naturally confirm the diagnosis of triple-negative breast cancer. Quota to be prepared as a fresh preparation for the two experiments of feasibility indicated above; quota to be considered as a second sample, to be analyzed at the end of the study.

Other: data collection; Collection of data relating to the effectiveness of sacituzumab govitecan and evaluation in a real-world context and planned research of predictive biomarkers of efficacy/tolerability

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomolecular investigations conducted on multiple platforms	Identify the predictive factors of the efficacy of sacituzumab govitecan in terms of PFS through biomolecular investigations conducted on multiple platforms, using tumor tissue (where possible both primary and metastatic) and peripheral blood, circulating plasma collected at two separate time points (T0 and T1) of mTNBC patients treated in the real-world setting.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS in patients.	Assess any differences in terms of PFS in patients treated in second line compared to patient treated in lines subsequent to the second. Evaluate the dynamics of quantitative variation over time of any circulating microRNAs predictive of efficacy and tolerability. Evaluate the differences in any predictive biomarkers of efficacy/tolerability, tissue and/or circulating, in patients treated in second line vs patients treated in subsequent lines. Assess any differences in PFS in relation to: previous treatment(s) in the early setting and metastatic, disease sites, dose reductions/treatment discontinuation.	30 months
Tolerability of the treatment	Evaluate the tolerability of the treatment in terms of adverse events, defined according to Common Terminology Criteria for Adverse Events (CTCAE, v. 5) and identify factors predictive of toxicity. Evaluate objective response rate (ORR) and overall survival (OS). Assess the variation in any biomarkers of efficacy in primary tumor tissue vs. tissue from metastatic localization (in cases where both samples are available). Select a small subgroup of patients from whose tumor tissue to develop organoids will be treated with SG, and on which potential will be quantified longitudinally over time biomarkers of response to treatment.	30 months
Development of organoids	Select a small subgroup of patients from the tumor tissue for single cell testing RNA sequencing to compare with data from bulk RNA sequencing to study the microenvironment tumoral.	30 months

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Catholic University of the Sacred Heart; Campus Bio-Medico University; Azienda Policlinico Umberto I; Ospedale Sandro Pertini, Roma; San Giovanni Addolorata Hospital; Hospital San Pietro Fatebenefratelli; Ospedale "SS Annunziata", Chieti; Ospedale "Gaetano Bernabeo" , Ortona; presidio Ospedaliero santo spirito in Sassia, Roma; Ospedale di Belcolle - Viterbo
• Investigators: Principal Investigator: Patrizia Vici, Doctor, IRCCS "Regina Elena" National Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2023
• Primary Completion (Estimated): January 17, 2025
• Study Completion (Estimated): June 17, 2025

Study Registration Dates

• First Submitted: January 12, 2024
• First Submitted That Met QC Criteria: January 26, 2024
• First Posted (Actual): February 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: RS1814/22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The Sponsor is the exclusive owner of all data and information arising from the study, including results, discoveries, know-how and the like.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No