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

Extensive-stage Small-cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04902885
• Other study ID #: B02B00801-TRILA-301
• Status: Completed
• Phase: Phase 3
• Start date: May 25, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: September 2021
• Source: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: December 31, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. -

Related Conditions & MeSH terms

• Extensive-stage Small-cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• Trilaciclib
Group 1: Trilaciclib, carboplatin, etoposide,or Topotecan Group 2: Trilaciclib, Topotecan Group 3: Placebo, carboplatin, etoposide,or Topotecan

Locations

Country	Name	City	State
China	Jilin Cancer Hopspital	Changchun

Sponsors (2)

Lead Sponsor	Collaborator
Jiangsu Simcere Pharmaceutical Co., Ltd.	G1 Therapeutics, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Plasma Concentration (Cmax) for part 1 study		At the end of Cycle 1 (each cycle is 21 days)
Primary	Time to reach peak concentration (Tmax) for part 1 study		At the end of Cycle 1 (each cycle is 21 days)
Primary	Half-life (T1/2) for part 1 study		At the end of Cycle 1 (each cycle is 21 days)
Primary	Area under the plasma concentration versus time curve (AUC) for part 1 study		At the end of Cycle 1 (each cycle is 21 days)
Primary	Incidence of Adverse Events (AEs) for part 1 and part 2 study		up to 30 days after last dose
Primary	Incidence of Serious Adverse Events (SAEs) for part 1 and part 2 study		up to 30 days after last dose
Primary	Incidence of AEs Leading to Study Drug Discontinuation for part 1 and part 2 study		up to 30 days after last dose
Primary	Duration of severe neutropenia (SN) in Cycle 1;		At the end of Cycle 1 (each cycle is 21 days)
Secondary	Incidence of SN;		during chemotherapy assessed up to 6 months
Secondary	Incidence of red blood cell (RBC) transfusion (at and after Week 5)		during chemotherapy assessed up to 6 months
Secondary	Incidence of G-CSF treatment;		during chemotherapy assessed up to 6 months
Secondary	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
Secondary	Incidence of Grade 3 and Grade 4 hematological toxicity;		during chemotherapy assessed up to 6 months
Secondary	Ctrough of absolute neutrophil count in each cycle;		during chemotherapy assessed up to 6 months
Secondary	Changes of absolute neutrophil count, platelet count, absolute lymphocyte count (ALC) and hemoglobin over time;		during chemotherapy assessed up to 6 months
Secondary	Incidence of ESA treatment;		during chemotherapy assessed up to 6 months
Secondary	The incidence of intravenous or oral antibiotics;		during chemotherapy assessed up to 6 months
Secondary	The incidence of serious infectious adverse events;		during chemotherapy assessed up to 6 months
Secondary	The incidence of serious adverse events of lung infection:		during chemotherapy assessed up to 6 months
Secondary	The incidence of febrile neutropenia;		during chemotherapy assessed up to 6 months
Secondary	The incidence of platelet transfusion		during chemotherapy assessed up to 6 months
Secondary	Objective response rate;		during chemotherapy assessed up to 6 months
Secondary	Disease control rate.		during chemotherapy assessed up to 6 months