Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Extensive-Stage Small Cell Lung Cancer Patients Receiving Carboplatin Combined With Etoposide or Topotecan

A Randomized, Double-blind, Placebo-controlled, Multi-center Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Extensive-Stage Small Cell Lung Cancer Patients Receiving Carboplatin Combined With Etoposide or Topotecan

A Randomized, double-blind, placebo-controlled, multi-center Phase 3 study evaluating efficacy, safety and pharmacokinetics of Trilaciclib In Extensive-Stage Small Cell Lung Cancer Patients Receiving Carboplatin combined with Etoposide or Topotecan The study consists of 2 parts: Part 1: safety run-in and pharmacokinetics evaluation of 12 ES-SCLC patients (6 each for first line and second/third line ES-SCLC patients); Part 2: randomized, double-blind, placebo-controlled efficacy confirmation study of 80 ES-SCLC patients (stratified by first line and second/third line ES-SCLC, ECOG PS [0-1 vs 2] and brain metastases.

The study includes screening period, treatment period, safety follow-up and survival follow-up.

Study Overview

• Status: Completed
• Conditions: Extensive-stage Small-cell Lung Cancer
• Intervention / Treatment: Drug: Trilaciclib

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Meina Yan, Doctor; Phone Number: +8618510219076; Email: yanmeina@simcere.com

Study Locations

• China
  • Changchun, China
    • Jilin Cancer Hopspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female of ≥ 18 years old;
2. Histology or cytology diagnosed extensive-stage small cell lung cancer ( ES-SCLC ) :
3. Patients who plan to receive carboplatin combined with etoposide: naïve with systemic treatment (such as chemotherapy or combined immunotherapy) in the past
4. Patients planning to receive topotecan : previously received 1/2 line chemotherapy or combined immunotherapy except for topotecan.
5. At least one measurable lesion without radiotherapy that meets RECIST1.1 standard;
6. Hemoglobin ≥ 90 g/L ;
7. Neutrophil count ≥ 1.5 × 109 /L ;
8. Platelet count ≥100 × 109 /L ;
9. Creatinine ≤ 15 mg /L or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula ) ;
10. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ;
11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN or ≤ 5 × ULN (patients with liver metastases) ;
12. Albumin ≥ 30 g/L ;
13. ECOG PS score:0-2 ;
14. Expected survival time ≥ 3 months ;
15. Contraception :
16. Women: Women with potential fertility must have a negative serum pregnancy test result at Screening, and take reliable contraceptive measures from signing informed consent to 3 months after the last administration ;
17. Male: If a female partner has potential fertility, reliable contraceptive measures must be taken after signing the informed consent to 3 months after the last administration.
18. Understand and sign the informed consent form.

Exclusion Criteria:

1. Symptomatic brain metastases that require local radiotherapy or hormone therapy;
2. Other history of malignant cancer, except for: (1) clinically cured basal cell or squamous cell tumors; (2) curable: a) cervical cancer, B) prostate cancer, C) superficial bladder cancer; or ( 3 ) any solid tumor that it is clinically cured for 3 years or above;
3. Uncontrolled ischemic heart disease or congestive heart failure with clinically significance (NYHA Class III or IV) ;
4. Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment ;
5. Severe active infection;
6. Potential inadequate compliance from psychological or other social factors;
7. Other uncontrolled severe chronic disease or condition, which considered by Investigator as unsuitable for study participation;
8. Known HIV infection, active hepatitis B (defined as HBV DNA positive) and hepatitis C (HCV RNA positive);
9. Received radiotherapy within 2 weeks before enrollment ;
10. Received cytotoxic or investigational drug treatment within 4 weeks, or non-cytotoxic anti-tumor treatment within 2 weeks before enrollment;
11. For Part 1 patients, concomitant administration of strong or moderate inducer of CYP3A4 within 4 weeks before study drug, or strong inhibitor of CYP3A4 within 2 weeks before study drug;
12. Recovery from previous toxicity of anti-tumor treatments to Level 0 or 1 (except for hair loss);
13. Allergy to the study drugs or any of their components (Trilaciclib, etoposide, carboplatin, topotecan);
14. Unable to act independently by legal restrictions or in the legal sense;
15. Women who are pregnant or breastfeeding ;
16. Other patients who are considered unsuitable to participate in the study. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Trilaciclib, carboplatin, etoposide; Trilaciclib plus Carboplatin combined with Etoposide (first line ES-SCLC patients)	Drug: Trilaciclib; Group 1: Trilaciclib, carboplatin, etoposide，or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide，or Topotecan; Other Names: Carboplatin combined with Etoposide (first line ES-SCLC patients); plus Topotecan (second/third line ES-SCLC patients)
Placebo Comparator: Placebo, carboplatin, etoposide; Placebo plus Carboplatin combined with Etoposide (first line ES-SCLC patients)	Drug: Trilaciclib; Group 1: Trilaciclib, carboplatin, etoposide，or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide，or Topotecan; Other Names: Carboplatin combined with Etoposide (first line ES-SCLC patients); plus Topotecan (second/third line ES-SCLC patients)
Active Comparator: Trilaciclib, Topotecan; plus Topotecan (second/third line ES-SCLC patients)	Drug: Trilaciclib; Group 1: Trilaciclib, carboplatin, etoposide，or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide，or Topotecan; Other Names: Carboplatin combined with Etoposide (first line ES-SCLC patients); plus Topotecan (second/third line ES-SCLC patients)
Placebo Comparator: Placebo, Topotecan; Placebo plus Topotecan (second/third line ES-SCLC patients)	Drug: Trilaciclib; Group 1: Trilaciclib, carboplatin, etoposide，or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide，or Topotecan; Other Names: Carboplatin combined with Etoposide (first line ES-SCLC patients); plus Topotecan (second/third line ES-SCLC patients)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak Plasma Concentration (Cmax) for part 1 study	At the end of Cycle 1 (each cycle is 21 days)
Time to reach peak concentration (Tmax) for part 1 study	At the end of Cycle 1 (each cycle is 21 days)
Half-life (T1/2) for part 1 study	At the end of Cycle 1 (each cycle is 21 days)
Area under the plasma concentration versus time curve (AUC) for part 1 study	At the end of Cycle 1 (each cycle is 21 days)
Incidence of Adverse Events (AEs) for part 1 and part 2 study	up to 30 days after last dose
Incidence of Serious Adverse Events (SAEs) for part 1 and part 2 study	up to 30 days after last dose
Incidence of AEs Leading to Study Drug Discontinuation for part 1 and part 2 study	up to 30 days after last dose
Duration of severe neutropenia (SN) in Cycle 1;	At the end of Cycle 1 (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of SN;		during chemotherapy assessed up to 6 months
Incidence of red blood cell (RBC) transfusion (at and after Week 5)		during chemotherapy assessed up to 6 months
Incidence of G-CSF treatment;		during chemotherapy assessed up to 6 months
4. Composite endpoints-important hematologic AEs (anyone of the followings):	All-cause hospitalization; All-cause dose reduction; Febrile neutropenia; Prolongation of Severe neutropenia (over 5 days); Infusion of red blood cell (RBC) infusion (at and after Week 5).	during chemotherapy assessed up to 6 months
Incidence of Grade 3 and Grade 4 hematological toxicity;		during chemotherapy assessed up to 6 months
Ctrough of absolute neutrophil count in each cycle;		during chemotherapy assessed up to 6 months
Changes of absolute neutrophil count, platelet count, absolute lymphocyte count (ALC) and hemoglobin over time;		during chemotherapy assessed up to 6 months
Incidence of ESA treatment;		during chemotherapy assessed up to 6 months
The incidence of intravenous or oral antibiotics;		during chemotherapy assessed up to 6 months
The incidence of serious infectious adverse events;		during chemotherapy assessed up to 6 months
The incidence of serious adverse events of lung infection:		during chemotherapy assessed up to 6 months
The incidence of febrile neutropenia;		during chemotherapy assessed up to 6 months
The incidence of platelet transfusion		during chemotherapy assessed up to 6 months
Objective response rate;		during chemotherapy assessed up to 6 months
Disease control rate.		during chemotherapy assessed up to 6 months

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Collaborators: G1 Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2021
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: May 8, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Etoposide; Topotecan
• Other Study ID Numbers: B02B00801-TRILA-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes