Using trilaciclib for early-stage HR-negative breast cancer patients receiving chemotherapy

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

This study is testing if the drug trilaciclib can help early-stage hormone receptor-negative breast cancer patients have fewer severe side effects from chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 116 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: trastuzumab, pertuzumab, chemotherapy, immunotherapy, cyclophosphamide
• Locations: 1 site (Guangzhou, Gangdong)
• Trial ID: NCT05978648 on ClinicalTrials.gov

What this trial studies

This exploratory clinical trial evaluates the efficacy and safety of trilaciclib in patients with early-stage hormone receptor-negative breast cancer undergoing standard adjuvant chemotherapy. Participants are divided into two cohorts based on molecular typing: one for triple-negative breast cancer patients and another for HER2-positive/HR-negative patients. The primary endpoint is the incidence of grade 3/4 neutropenia, which will help determine the effectiveness of trilaciclib when administered before chemotherapy. The study aims to improve treatment outcomes for these patients by potentially reducing chemotherapy-related side effects.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed early-stage HR-negative breast cancer who are set to receive adjuvant chemotherapy.

Not a fit: Patients with metastatic breast cancer or those whose tumors do not meet the specified molecular criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could reduce the incidence of severe neutropenia in patients undergoing chemotherapy for early-stage HR-negative breast cancer.

How similar studies have performed: While the use of trilaciclib is a novel approach in this specific context, similar studies have shown promise in managing chemotherapy-related side effects in other cancer types.

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.

Where this trial is running

Guangzhou, Gangdong

• Sun-yat sen university cancer center — Guangzhou, Gangdong, China (Recruiting)

Study contacts

• Principal investigator: Shusen Wang, MD — Sun Yat-sen University
• Study coordinator: Shusen Wang, MD

Conditions Breast Neoplasms; Trilaciclib; HR-Negative Breast Cancer; Adjuvant Therapy