Bone Marrow Protection, Safety, Efficacy of Trilaciclib and Eribulin in Locally Advanced or Metastatic TNBC(Triple-negative Breast Cancer)

Official title

A Single-arm, Phase II Study for Bone Marrow Protection, Safety, and Efficacy of Trilaciclib Combined With Eribulin in Locally Advanced or Metastatic Triple-negative Breast Cancer After at Least Two Prior Chemotherapy Regimens

Overview

Triple negative breast cancer (TNBC) has attracted much attention due to its young age of onset, high aggressiveness, lack of clear therapeutic targets and poor clinical prognosis.Eribulin is a novel non-taxane anti-microtubule inhibitor with unique microtubule and non-microtubule anti-tumor mechanism.Myelosuppression is the cause of many cancer chemotherapy-related adverse events, such as infections, sepsis, bleeding, and fatigue, resulting in delayed hospital stays or the need for treatment with hematopoietic growth factors, blood transfusions, and more.In addition, myelosuppression usually leads to a lower dose or longer interval of chemotherapy, which reduces the intensity of chemotherapy and affects the benefit of chemotherapy for patients.Trilaciclib is a highly potent, selective and reversible CDK4/6 inhibitor that protects bone marrow by protecting hematopoietic stem cells and progenitor cells (HSPCs) during systemic chemotherapy.

Detailed description

Four randomized, double-blind clinical trials of treacilil in patients with small cell lung cancer (SCLC) confirmed that Trilaciclib administration in combination with chemotherapy prevented or mitigated chemotherapy-induced myelosuppression.Among them, the G1T28-05 study showed that the administration of Trilaciclib before first-line chemotherapy (carboplatin combined with etoposide) could reduce the duration of severe neutropenia in the first cycle from 4 days to 0 days, and the incidence of severe neutropenia from 49.1% to 1.9%.As the world's first drug designed to reduce chemotherapy-induced myelosuppression by protecting HSPCs, Trilaciclib has demonstrated a significant ability to prevent chemotherapy-mediated multicellular lineage myelosuppression in patients with ES-SCLC.In February 2021, the U.S. Food and Drug Administration (FDA) approved Trilaciclib (COSELA™) to reduce the incidence of chemotherapy-induced myelodepression in adult patients with extensive stage small cell lung cancer prior to receiving a platinum-containing/etoposide regimen or topotecan regimen.

Based on the evidence that Trilaciclib has been approved by the FDA to reduce the incidence of chemotherapy-induced myelopathic depression in adult patients with extensive stage small cell lung cancer prior to receipt of a platinum-containing/etoposide regimen or topotecan regimen, there is encouraging patient outcome improvement observed in study G1T28-04.This Phase II clinical trial was designed to confirm the bone marrow protection and efficacy and safety of Trilaciclib in patients with locally advanced/metastatic TNBC who had previously received at least two chemotherapy regimes prior to treatment with Eribulin.

Interventions

• Drug Trilaciclib
  Each participant receives Trilaciclib(240mg/m², intravenous infusion for 30 minutes, and completed within 4 hours before chemotherapy administration on day 1 and day 8, day 21 was 1 cycle)
• Drug Eribulin
  Each participant receives Eribulin(1.4mg/m², intravenous infusion at day 1 and day 8, with 1 cycle at day 21)

Primary outcome measures

• Prevalence of grade 3 neutropenia during cycle 1-2 of chemotherapy treatment [Time frame: 6 months]

Secondary outcome measures (7)

• Anti-tumor efficacy [Time frame: 6 months]
• Adverse events, abnormal laboratory tests, etal [Time frame: 6 months]
• Bone marrow protection [Time frame: 6 months]
• Disease burden(cost) [Time frame: 6 months]
• Disease burden(in-stay time) [Time frame: 6 months]
• Disease burden(quality of life) [Time frame: 6 months]
• Compliance with the chemotherapy regimen [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• ≥18 years old , no limitation of gender;
• locally advanced or metastatic triple-negative breast cancer;
• have received at least two prior chemotherapy regimens(The recurrence of the last adjuvant chemotherapy is counted one line within 12 months after surgery);
• At least one measurable lesion according to RECIST version 1.1;
• The laboratory tests meet the following criteria:

Hemoglobin: ≥ 100 g / L (female), 110g / L (male) Neutrophil count : ≥2×10\^9/L Platelet count: ≥100×10\^9/L Creatinine：≤15mg / L or creatinine clearance (CrCl) ≥60 mL/min (Cockcroft-Gault formula); Total bilirubin：≤1.5× upper limit of normal (ULN) Alutamate aminotransferase (ALT) and glutamate aminotransferase (AST)≤ 3 ×ULN or 5 ×ULN (for patients with liver metastases) Albumin: ≥ 30 g / L;

• Eastern Cooperative Oncology Group (ECOG) score \[0-1\] points;
• The expected survival period is ≥3 months;
• During the screening period, all female with potential fertility must have negative serum pregnancy tests and reliable contraception after signing the informed consent form until 3 months after the last dose;
• Comprehend and voluntarily sign the informed consent form;

Exclusion criteria

• Diagnosed other malignant disease besides breast cancerwithin 5 years before the first dose (excluding radical skin basal cell carcinoma, skin squamous epithelial carcinoma, and / or radical resection);
• Main organ function not good enough;
• Bone marrow invasion;
• Require combined chemotherapy other than Eribulin;
• Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment;
• QTcF > 480 msec ( screening period) and QTcF> 500 msec for patients with ventricular pacemaker implantation;
• Previous hematopoietic stem cell or bone marrow transplantation;
• Previous G-CSF treatment in the last 2 weeks;
• Allergic to the study drug or the ingredients;
• Any other situation where the researcher considers the patient not suitable to participate in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07255612 · PROTECTION

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗