The Study of Trilaciclib Combined With Chemotherapy On The Neoadjuvant Therapy of TNBC

Official title

A Prospective, Randomized, Controlled Phase II Clinical Study of Trilaciclib Combined With Standard Treatment Project As a Neoadjuvant Treatment For Triple Negative Breast Cancer

Overview

To evaluate the efficacy and safety of trilaciclib combined with standard treatment project as a neoadjuvant treatment for triple negative breast cancer

Detailed description

Trilaciclib indication: Trilaciclib, a CDK4/6 inhibitor, was used before chemotherapy to reduce the incidence of bone marrow suppression and approved by the FDA for small cell lung cancer patients in 2021.

Interventions

• Drug Trilaciclib plus chemotherapy
  Trilaciclib: 240mg/m2 IV d1,within 4h before chemotherapy epirubicin: 100mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles cyclophosphamide:600mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles albumin-bound paclitaxel:100mg/m2 IV d1,8,15,Q3W,4cycles
• Drug Chemotherapy
  epirubicin: 100mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles cyclophosphamide:600mg/m2 IV d1,Q2W/Q3W (decided by researchers),4 cycles albumin-bound paclitaxel:100mg/m2 IV d1,8,15,Q3W,4cycles

Primary outcome measures

• The incidence of CIN [Time frame: From date of randomization until the date of surgery, assessed up to 6 months]

Secondary outcome measures (7)

• The incidence of CIT [Time frame: From date of randomization until the date of surgery, assessed up to 6 months]
• The incidence of CIA [Time frame: From date of randomization until the date of surgery, assessed up to 6 months]
• pCR rate [Time frame: From date of randomization until the date of surgery, assessed up to 6 months.]
• ORR [Time frame: From date of randomization until the date of PD (up to 24 months)]
• OS [Time frame: From date of randomization until the date of death(up to 24 months)]
• DFS [Time frame: From date of randomization until the date of toxicity or PD (up to 24 months)]
• Adverse event [Time frame: Frame:From date of randomization until the date of toxicity or PD (up to 24 months)]

Eligibility criteria

Inclusion criteria

• Newly treated patients aged ≥ 18 years;
• ECOG score 0-1;
• Breast cancer meets the following standards:

• Histologically confirmed invasive breast cancer
• Tumor staging: cT2-4, cNany, cM0 or cT1, cN1-3, cM0;
• Hormone (estrogen and progesterone) receptor negative tumors confirmed by histological or cytological records (defined as nuclear staining rate<1% based on immunohistochemistry \[IHC\] evaluation) and Her-2 negative, non overexpressing tumors (based on IHC \[0 or 1+\] or in situ hybridization \[ratio<2.0\] or average Her-2 gene copy number<4 signals/nucleus);
• Within the first two weeks of the screening period, no G-CSF, TPO, IL-11, ESA, iron, platelet transfusion, or blood transfusion have been used.
• The functional level of the main organs must meet the following requirements:

• Blood routine: Neutrophils (ANC)≥1.5×109/L, platelet count (PLT)≥90×109/L, hemoglobin (Hb)≥90g/L
• Blood biochemistry: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, serum creatinine (Cr)≤1.5×ULN, bilirubin<1.5 ULN;
• For female patients who have not undergone menopause or surgical sterilization: During the treatment period and at least 7 months after the last dose in the study treatment, consent to abstinence or use effective contraceptive methods.
• Volunteer join this study, sign an informed consent form, have good compliance, and are willing to cooperate with follow-up.

Exclusion criteria

• Previously received anti-tumor treatment for any malignant tumor;
• Subjects who are unable to accept or tolerate preoperative chemotherapy due to various reasons;
• The patient has undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or has not fully recovered from such surgical procedures;
• Serious heart disease or discomfort, including but not limited to the following diseases:

• A confirmed history of heart failure or systolic dysfunction (LVEF<50%);
• High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate>100bpm, significant ventricular arrhythmias (such as ventricular tachycardia) or higher-level atrioventricular block (such as Mobitz II second degree atrioventricular block or third degree atrioventricular block);
• Angina pectoris requiring treatment with anti angina drugs;
• Heart valve disease with clinical significance;
• ECG shows transmural myocardial infarction;
• Poor control of hypertension (systolic blood pressure>180mmHg and/or diastolic blood pressure>100mmHg)
• Those with a known history of allergies to the drug components of this protocol;
• Breastfeeding female patients, those with fertility and positive baseline pregnancy test results, or those of childbearing age who are unwilling to take effective contraceptive measures during the entire trial period and within 7 months after the last study medication;
• Any other circumstances in which the researcher believes that the patient is 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

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Weiss JM, Csoszi T, Maglakelidze M, Hoyer RJ, Beck JT, Domine Gomez M, Lowczak A, Aljumaily R, Rocha Lima CM, Boccia RV, Hanna W, Nikolinakos P, Chiu VK, Owonikoko TK, Schuster SR, Hussein MA, Richards DA, Sawrycki P, Bulat I, Hamm JT, Hart LL, Adler S, Antal JM, Lai AY, Sorrentino JA, Yang Z, Malik RK, Morris SR, Roberts PJ, Dragnev KH; G1T28-02 Study Group. Myelopreservation with the CDK4/6 inhi PMID 31504118
• Daniel D, Kuchava V, Bondarenko I, Ivashchuk O, Reddy S, Jaal J, Kudaba I, Hart L, Matitashvili A, Pritchett Y, Morris SR, Sorrentino JA, Antal JM, Goldschmidt J. Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial. Int J Cancer. 2021 May 15;148(10):255 PMID 33348420
• Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, Hanna WT, Aljumaily R, Owonikoko TK, Verhoeven D, Xiao J, Morris SR, Antal JM, Hussein MA. Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Adv Ther. 2021 Jan;38(1):350-365. doi: 10.1007/s12325 PMID 33123968
• Weiss J, Goldschmidt J, Andric Z, Dragnev KH, Gwaltney C, Skaltsa K, Pritchett Y, Antal JM, Morris SR, Daniel D. Effects of Trilaciclib on Chemotherapy-Induced Myelosuppression and Patient-Reported Outcomes in Patients with Extensive-Stage Small Cell Lung Cancer: Pooled Results from Three Phase II Randomized, Double-Blind, Placebo-Controlled Studies. Clin Lung Cancer. 2021 Sep;22(5):449-460. doi: PMID 33895103
• Lai AY, Sorrentino JA, Dragnev KH, Weiss JM, Owonikoko TK, Rytlewski JA, Hood J, Yang Z, Malik RK, Strum JC, Roberts PJ. CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy. J Immunother Cancer. 2020 Oct;8(2):e000847. doi: 10.1136/jitc-2020-000847 PMID 33004541

Identifiers

NCT: NCT05862610 · SMA-BC-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗