Clinical trial NCT05862610: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Breast Neoplasm
Keywords: Trilaciclib/TNBC/Neoadjuvant
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2023-05-17
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of CIN
timeFrame: From date of randomization until the date of surgery, assessed up to 6 months
Secondary outcomes:
measure: The incidence of CIT
timeFrame: From date of randomization until the date of surgery, assessed up to 6 months
measure: The incidence of CIA
timeFrame: From date of randomization until the date of surgery, assessed up to 6 months
measure: pCR rate
timeFrame: From date of randomization until the date of surgery, assessed up to 6 months.
measure: ORR
timeFrame: From date of randomization until the date of PD (up to 24 months)
measure: OS
timeFrame: From date of randomization until the date of death(up to 24 months)
measure: DFS
timeFrame: From date of randomization until the date of toxicity or PD (up to 24 months)
measure: Adverse event
timeFrame: Frame:From date of randomization until the date of toxicity or PD (up to 24 months)
Other outcomes:
Locations:
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Qiang Liu, Doc
role: STUDY_CHAIR
References:
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.
citation: 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):2557-2570. doi: 10.1002/ijc.33453. Epub 2021 Jan 12.
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.
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.
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.