Trilaciclib in Combination With Docetaxel for Second-Line and Beyond Treatment of Locally Advanced or Metastatic NSCLC

Official title

Phase II Clinical Trial of Trilaciclib in Combination With Docetaxel for Second-Line and Beyond Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Overview

This study is a prospective, single arm phase II study aimed at patients with locally advanced or metastatic non-small cell lung cancer undergoing second-line or beyond treatment. The aim is to evaluate the bone marrow protective effect of trilaciclib before docetaxel chemotherapy for locally advanced or metastatic NSCLC.

Detailed description

After obtaining informed consent from patients diagnosed with locally advanced or metastatic NSCLC through pathology, 33 eligible subjects who met the inclusion criteria were selected to receive the treatment regimen of trilaciclib before docetaxel chemotherapy, with a treatment period of 4 cycles.

Record the dynamic changes of whole blood cell count; Hematological toxicity, including febrile neutropenia and associated infections; Transfusion of blood products and supplementation of hematopoietic raw materials. Perform tumor imaging evaluation according to RECIST 1.1. Baseline imaging examination shall be conducted within 21 days prior to the first administration, and tumor imaging evaluation shall be conducted every 6 weeks (± 7 days) from the first study drug administration, or the frequency of imaging evaluation may be increased when there are clinical indications. The imaging examination time should follow the calendar day and should not be adjusted due to treatment delay or termination. Subjects who terminate the study drug treatment due to intolerable toxicity or other non disease progression reasons should continue to receive tumor evaluation follow-up until disease progression, withdrawal from the study, or death (whichever occurs earliest)

Interventions

• Drug Trilaciclib combined with Docetaxel
  Trilaciclib: 240 mg/m2 as a 30-min iv. infusion, completed ≤4h prior to chemotherapy. Docetaxel: 75mg/m2, iv. infusion for 1 hour on days 1 of each 21-day cycle, totaling 4 cycles of medication.

Primary outcome measures

• Incidence of grade ≥ 3 neutropenia during chemotherapy treatment [Time frame: Time from date of first dose of trilaciclib and docetaxel through 30 days following the last dose of trilaciclib and docetaxel]

Secondary outcome measures (10)

• Incidence rate of grade 3 or 4 thrombocytopenia [Time frame: Time from date of first dose of trilaciclib and docetaxel through 30 days following the last dose of trilaciclib and docetaxel]
• Incidence rate of grade 3 or 4 anemia during chemotherapy treatment [Time frame: Time from date of first dose of trilaciclib and docetaxel through 30 days following the last dose of trilaciclib and docetaxel]
• Incidence rate of febrile neutropenia [Time frame: Time from date of first dose of trilaciclib and docetaxel through 30 days following the last dose of trilaciclib and docetaxel]
• Usage rate of symptomatic treatments for myelosuppression [Time frame: Time from date of first dose of trilaciclib and docetaxel through 30 days following the last dose of trilaciclib and docetaxel]
• Objective response rate [Time frame: 12 months after the last subject participating in]
• Disease control rate [Time frame: 12 months after the last subject participating in]
• Duration of response [Time frame: 12 months after the last subject participating in]
• Progression-free survival [Time frame: 12 months after the last subject participating in]
• Overall survival [Time frame: From the date of randomization to the date of death for patients who died in the study due to any cause, or to the last contact date known to be alive for those who survived as of the data cutoff date, assessed up to 30 months.]
• Incidence rate of adverse events [Time frame: Time from date of first dose of trilaciclib and docetaxel through 90 days following the last dose of trilaciclib and docetaxel]

Eligibility criteria

Inclusion criteria

Patients must meet all of the following inclusion criteria to be included in this study:

• Age ≥ 18 years old, regardless of gender;
• Patients with stage IV NSCLC who have failed at least one line of standard treatment regimen:

A. Patients with negative driver genes must have received first line standard treatment (chemotherapy combined with immunotherapy).

B. Patients with positive driver genes must have received at least one line chemotherapy after standard targeted therapy has failed.

C. Definition of driver genes: EGFR (including 19del, L858R, S768I, L861Q, and/or G719X), BRAF V600E, NTRK, MET14 exon skipping mutation, RET, ROS1, etc.

• At least one measurable lesion that meets the RECIST 1.1 criteria exists;
• The laboratory test results meet the following criteria:

Hemoglobin ≥ 100 g/L (female), 110g/L (male) ,Neutrophil count ≥ 2×109/L Platelet count ≥ 100×109/L; Creatinine ≤15mg/L or creatinine clearance rate (CrCl) ≥ 60mL/min (Cockcroft Gault formula); Total bilirubin ≤ 1.5xupper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN or ≤ 5×ULN (for patients with liver metastases); Albumin ≥ 30 g/L;

• ECOG PS score 0-2;
• Expected survival time ≥ 3 months;
• Women: All women with potential fertility must have a negative serum pregnancy test result during the screening period, and must take reliable contraceptive measures from signing the informed consent form until 3 months after the last dose;
• Understand and sign the informed consent form.

Exclusion criteria

• Previously received treatment with docetaxel;
• Diagnosed with malignant diseases other than NSCLC within 5 years prior to the first administration (excluding curative basal cell carcinoma, squamous cell carcinoma, and/or excised carcinoma in situ);
• Uncontrolled ischemic heart disease or clinically significant congestive heart failure (NYHA class III or IV);
• Stroke or cardiovascular events within the first 6 months of enrollment;
• When screening, if the QTcF interval is greater than 480 milliseconds, for patients implanted with ventricular pacemakers, QTcF>500msec；
• Human immunodeficiency virus (HIV) infected individuals (HIV 1/2 antibody positive), known syphilis infected individuals;
• Previously received hematopoietic stem cell or bone marrow transplantation;
• Allergies to research drugs or their components;
• The researchers believe that it 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

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Xiamen University — Xiamen

Identifiers

NCT: NCT06929936 · PROTECT-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗