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

Sponsor

wang shusen (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05978648

Collaborator

(none)

116

Enrollment

Location

Arms

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Trilaciclib Drug: Epirubicin Drug: Cyclophosphamide Drug: Paclitaxel Drug: Docetaxel Drug: Carboplatin Drug: Trastuzumab Drug: Pertuzumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

116 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2026

Anticipated Study Completion Date :

Dec 31, 2027

Arms and Interventions

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: COSELA® G1T28 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: COSELA® G1T28 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.

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:

COSELA®

G1T28

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:

COSELA®

G1T28

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.

Outcome Measures

Primary Outcome Measures

Occurrence of Grade 3/4 neutropenia [Up to 24 weeks]
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

Secondary Outcome Measures

Neutrophil-related myeloprotective effects [Up to 24 weeks]
Occurrence of febrile neutropenia adverse events(AEs) , and occurrence of Granulocyte colony-stimulating factor(G-CSF) administration
Red blood cell(RBC) -related myeloprotective effects [Up to 24 weeks]
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
Platelet-related myeloprotective effects [Up to 24 weeks]
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
Myeloprotective Effects [Up to 24 months]
Hospitalization due to chemotherapy-induced myelosuppression, dose reductions and delays, relative dose intensity(RDI) of chemotherapeutic agents
Safety and tolerability [Up to 24 months]
Incidence of Treatment-Emergent Adverse Events as per CTCAE version 5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.