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

Breast Neoplasm Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05862610
• Other study ID #: SMA-BC-001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 30, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: July 2023
• Source: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Contact: Qiang Liu, Doc
• Phone: 020-81332199
• Email: victorlq[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: June 30, 2027
• Est. primary completion date: December 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

1. Histologically confirmed invasive breast cancer

2. 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:

1. Blood routine: Neutrophils (ANC)=1.5×109/L, platelet count (PLT)=90×109/L, hemoglobin (Hb)=90g/L

2. 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:

1. A confirmed history of heart failure or systolic dysfunction (LVEF<50%);

2. 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);

3. Angina pectoris requiring treatment with anti angina drugs;

4. Heart valve disease with clinical significance;

5. ECG shows transmural myocardial infarction;

6. 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.

Related Conditions & MeSH terms

• Breast Neoplasm
• Breast Neoplasms

Intervention

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
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

References & Publications (5)

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. 2020 Dec 21;148(10):2557-70. doi: 10.1002/ijc.33453. Online ahead of print. — View Citation

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/s12325-020-01538-0. Epub 2020 Oct 29. — View Citation

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. — View Citation

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: 10.1016/j.cllc.2021.03.010. Epub 2021 Mar 26. — View Citation

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 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019 Oct 1;30(10):1613-1621. doi: 10.1093/annonc/mdz278. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of CIN	The incidence of =3 grade neutropenia	From date of randomization until the date of surgery, assessed up to 6 months
Secondary	The incidence of CIT	The incidence of =3 grade thrombopenia	From date of randomization until the date of surgery, assessed up to 6 months
Secondary	The incidence of CIA	The incidence of =3 grade anemia	From date of randomization until the date of surgery, assessed up to 6 months
Secondary	pCR rate	Rate of pCR using the definition of ypT0/Tis ypN0 as assessed by the local pathologist.	From date of randomization until the date of surgery, assessed up to 6 months.
Secondary	ORR	Objective Response Rate	From date of randomization until the date of PD (up to 24 months)
Secondary	OS	Overall survival	From date of randomization until the date of death(up to 24 months)
Secondary	DFS	Disease-free survival	From date of randomization until the date of toxicity or PD (up to 24 months)
Secondary	Adverse event	Number of participants with adverse events as a measure of safety and tolerability	Frame:From date of randomization until the date of toxicity or PD (up to 24 months)