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

Sponsor
Jiangsu Simcere Pharmaceutical Co., Ltd. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04902885
Collaborator
G1 Therapeutics, Inc. (Industry)
92
Enrollment
1
Location
4
Arms
21.7
Anticipated Duration (Months)
4.2
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
92 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 25, 2021
Anticipated Primary Completion Date :
Oct 20, 2021
Anticipated Study Completion Date :
Mar 15, 2023

Arms and Interventions

ArmIntervention/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)
  • Outcome Measures

    Primary Outcome Measures

    1. Peak Plasma Concentration (Cmax) for part 1 study [At the end of Cycle 1 (each cycle is 21 days)]

    2. Time to reach peak concentration (Tmax) for part 1 study [At the end of Cycle 1 (each cycle is 21 days)]

    3. Half-life (T1/2) for part 1 study [At the end of Cycle 1 (each cycle is 21 days)]

    4. Area under the plasma concentration versus time curve (AUC) for part 1 study [At the end of Cycle 1 (each cycle is 21 days)]

    5. Incidence of Adverse Events (AEs) for part 1 and part 2 study [up to 30 days after last dose]

    6. Incidence of Serious Adverse Events (SAEs) for part 1 and part 2 study [up to 30 days after last dose]

    7. Incidence of AEs Leading to Study Drug Discontinuation for part 1 and part 2 study [up to 30 days after last dose]

    8. Duration of severe neutropenia (SN) in Cycle 1; [At the end of Cycle 1 (each cycle is 21 days)]

    Secondary Outcome Measures

    1. Incidence of SN; [during chemotherapy assessed up to 6 months]

    2. Incidence of red blood cell (RBC) transfusion (at and after Week 5) [during chemotherapy assessed up to 6 months]

    3. Incidence of G-CSF treatment; [during chemotherapy assessed up to 6 months]

    4. 4. Composite endpoints-important hematologic AEs (anyone of the followings): [during chemotherapy assessed up to 6 months]

      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).

    5. Incidence of Grade 3 and Grade 4 hematological toxicity; [during chemotherapy assessed up to 6 months]

    6. Ctrough of absolute neutrophil count in each cycle; [during chemotherapy assessed up to 6 months]

    7. Changes of absolute neutrophil count, platelet count, absolute lymphocyte count (ALC) and hemoglobin over time; [during chemotherapy assessed up to 6 months]

    8. Incidence of ESA treatment; [during chemotherapy assessed up to 6 months]

    9. The incidence of intravenous or oral antibiotics; [during chemotherapy assessed up to 6 months]

    10. The incidence of serious infectious adverse events; [during chemotherapy assessed up to 6 months]

    11. The incidence of serious adverse events of lung infection: [during chemotherapy assessed up to 6 months]

    12. The incidence of febrile neutropenia; [during chemotherapy assessed up to 6 months]

    13. The incidence of platelet transfusion [during chemotherapy assessed up to 6 months]

    14. Objective response rate; [during chemotherapy assessed up to 6 months]

    15. Disease control rate. [during chemotherapy assessed up to 6 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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. -

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Jilin Cancer HopspitalChangchunChina

    Sponsors and Collaborators

    • Jiangsu Simcere Pharmaceutical Co., Ltd.
    • G1 Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jiangsu Simcere Pharmaceutical Co., Ltd.
    ClinicalTrials.gov Identifier:
    NCT04902885
    Other Study ID Numbers:
    • B02B00801-TRILA-301
    First Posted:
    May 26, 2021
    Last Update Posted:
    Sep 8, 2021
    Last Verified:
    Sep 1, 2021
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 8, 2021