Trilaciclib in Patients With Early-Stage HR-negative Breast Cancer Receiving Adjuvant Chemotherapy (SMA-BC-002)

A Prospective, Multi-cohort, Exploratory Phase II Study of Trilaciclib Combined With Standard Chemotherapy in The Adjuvant Treatment of Hormone Receptor (HR) Negative Breast Cancer

The goal of this multicenter, two-cohort, exploratory clinical trial is to evaluate patients with early stage hormone receptor-negative breast cancer receiving standard adjuvant chemotherapy after surgery. The main question it aims to answer is:

• The efficacy and safety of trilaciclib administered before standard adjuvant chemotherapy regimen using the incidence of grade 3/4 neutropenia as the primary efficacy endpoint.

Participants will divide into two treatment cohorts according to molecular typing type:

• Cohort A will be planned to include post-operative triple-negative breast cancer(TNBC) patients with lymph node positive or tumor > 2 cm treated with trilaciclib combined with epirubicin and cyclophosphamide followed by weekly paclitaxel;
• Cohort B will be planned to include HER2-positive/HR-negative breast cancer patients with axillary node positive or tumor > 2 cm treated with trilaciclib combined with docetaxel, carboplatin and trastuzumab with or without pertuzumab.

Study Overview

• Status: Recruiting
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Trilaciclib; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Docetaxel; Drug: Carboplatin; Drug: Trastuzumab; Drug: Pertuzumab

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: shusen wang, MD; Phone Number: +86-13926168469; Email: wangshs@sysucc.org.cn

Study Locations

• China
  • Gangdong
    • Guangzhou, Gangdong, China, 510060
      • Recruiting
      • Sun-Yat Sen University Cancer Center
      • Contact: shusen wang, MD; Phone Number: +86-13926168469; Email: wangshs@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• age ≥ 18 years;

• breast cancer meets the following criteria:

  • Histologically or cytologically confirmed and adequately resected non-metastatic primary invasive breast cancer;
  • Cohort A only: ER, PR negative (< 1% nuclear staining as assessed by immunohistochemistry [IHC]), HER2 negative (HER2/CEP17 ratio < 2.0 or mean HER2 gene copy number < 4 signals/nucleus detected by IHC 0 or 1 + or in situ hybridization [ISH]); patients with concurrent bilateral invasive disease met the inclusion criteria if both lesions were HR negative/HER2 negative.
  • Cohort B only: ER, PR negative (< 1% nuclear staining as assessed by immunohistochemistry [IHC]); HER2 positive: HER2/CEP17 ratio ≥ 2.0 or HER2 gene copy number ≥ 4 signals/nucleus detected by IHC 3 + and ISH; HER2 gene copy number ≥ 6 signals/nucleus detected by IHC 3 + or 2 + and ISH); patients with concurrent bilateral invasive disease met the inclusion criteria if both lesions were HR negative/HER2 positive.
  • Subjects must have positive lymph nodes or tumors > 2 cm;
  • The interval between radical surgery and the first dose ≤ 60 days;
• Eastern Cooperative Oncology Group (ECOG) performance score 0-1;
• have appropriate organ function, meet the following criteria: (1) have appropriate bone marrow function: Hb ≥ 100 g/L (no ESA and blood transfusion within 14 days before the first dose); absolute neutrophil count (ANC) ≥ 2 × 10^9/L (no G-CSF within 14 days before the first dose); platelet count ≥ 100 × 10^9/L (no rhTPO/rhIL-11 and platelet transfusion within 14 days before the first dose); (2) appropriate liver and kidney function: alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN, serum creatinine ≤ 1.5 × ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula); (3) appropriate cardiac function: left ventricular ejection fraction (LVEF) ≥ 55%;
• Non-hematologic toxicities from prior surgical procedures recovered to ≤ Grade 1 or baseline (except alopecia);
• Females of childbearing potential agree to practice reliable contraception during the clinical trial and have a negative serum or urine pregnancy test within 7 days prior to dosing;
• Voluntarily join this study and sign informed consent, have good compliance and are willing to cooperate with follow-up.

Exclusion Criteria:

• Prior neoadjuvant therapy (including chemotherapy, targeted therapy, immunotherapy, or radiotherapy);
• History of other malignancy within 5 years prior to first dose, except basal cell carcinoma and cervical carcinoma in situ;
• Any T4 or N2 or known N3 or M1 breast cancer;
• Subjects who cannot receive or tolerate postoperative chemotherapy for various reasons;

• Heart disease ineligible for epirubicin, docetaxel, trastuzumab/pertuzumab:

  • Any documented history of myocardial infarction, congestive heart failure
  • Angina pectoris requiring antianginal medication
  • Grade 3 or 4 cardiac arrhythmia (NCI CTCAEv5.0)
  • Clinically significant valvular heart disease;
  • Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)
• Known history of hypersensitivity to the drug components of this protocol;
• Any other condition that, in the opinion of the investigator, would make the patient inappropriate for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Triple-negative Breast Cancer; Cohort A Administered Trilaciclib in Combination with Chemotherapy(EC-wP)	Drug: Trilaciclib; 240 mg/m2, intravenous drip over 30 min within 4 hours before chemotherapy administration on the same day; Other Names: G1T28; COSELA®; Drug: Epirubicin; 90 mg/m2, intravenous drip, d1, Q3W, 4 cycles.; Drug: Cyclophosphamide; 600 mg/m2, intravenous drip, d1, Q3W, 4 cycles.; Drug: Paclitaxel; 80 mg/m2, intravenous drip, d1,8,15, Q3W, 4 cycles.
Experimental: Cohort B: ER-negative PR-negative Her2-positive Breast Cancer; Cohort B Administered Trilaciclib in Combination with Chemotherapy(TCbH±P)	Drug: Trilaciclib; 240 mg/m2, intravenous drip over 30 min within 4 hours before chemotherapy administration on the same day; Other Names: G1T28; COSELA®; Drug: Docetaxel; 75 mg/m2, intravenous drip, d1, Q3W, 6 cycles.; Drug: Carboplatin; area under curve(AUC) = 6, intravenous drip, d1, Q3W, 6 cycles.; Drug: Trastuzumab; 8 mg/kg in Cycle 1, 6 mg/kg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.; Drug: Pertuzumab; 840mg in Cycle 1, 420mg in subsequent cycles, intravenous drip, d1, Q3W, for 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Grade 3/4 neutropenia	Proportion of subjects with at least one absolute neutrophil count (ANC) < 1.0 × 10^9/L enrolled and treated with at least one dose of trilaciclib	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil-related myeloprotective effects	Occurrence of febrile neutropenia adverse events(AEs) , and occurrence of Granulocyte colony-stimulating factor(G-CSF) administration	Up to 24 weeks
Red blood cell(RBC) -related myeloprotective effects	Occurrence of Grade 3/4 decrease of hemoglobin, occurrence and number of RBC transfusions on/after Week 5, and occurrence of erythropoiesis-stimulating agent(ESA) administration	Up to 24 weeks
Platelet-related myeloprotective effects	Occurrence of Grade 3/4 decrease of platelets, occurrence and number of platelet transfusions, and occurrence of rhTPO/Recombinant human interleukin-11(rhIL-11) administration	Up to 24 weeks
Myeloprotective Effects	Hospitalization due to chemotherapy-induced myelosuppression, dose reductions and delays, relative dose intensity(RDI) of chemotherapeutic agents	Up to 24 months
Safety and tolerability	Incidence of Treatment-Emergent Adverse Events as per CTCAE version 5.0	Up to 24 months

Collaborators and Investigators

• Sponsor: wang shusen
• Investigators: Principal Investigator: Shusen Wang, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 18, 2023
• First Submitted That Met QC Criteria: July 30, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Trilaciclib; HR-Negative Breast Cancer; Adjuvant Therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Carboplatin; Paclitaxel; Trastuzumab; Epirubicin; Pertuzumab
• Other Study ID Numbers: SMA-BC-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes