Clinical trial NCT05978648: Trilaciclib in Patients With Early-Stage HR-negative Breast Cancer Receiving Adjuvant Chemotherapy
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Neoplasms
Keywords: Trilaciclib; HR-Negative Breast Cancer; Adjuvant Therapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-08-07
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of Grade 3/4 neutropenia
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Neutrophil-related myeloprotective effects
timeFrame: Up to 24 weeks
measure: Red blood cell(RBC) -related myeloprotective effects
timeFrame: Up to 24 weeks
measure: Platelet-related myeloprotective effects
timeFrame: Up to 24 weeks
measure: Myeloprotective Effects
timeFrame: Up to 24 months
measure: Safety and tolerability
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun-yat sen university cancer center
state: Gangdong
Study officials:
affiliation: Sun Yat-sen University
name: Shusen Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: