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
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 Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| 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:
|
| 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:
|
| 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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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): [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).
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female of ≥ 18 years old;
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Histology or cytology diagnosed extensive-stage small cell lung cancer ( ES-SCLC ) :
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Patients who plan to receive carboplatin combined with etoposide: naïve with systemic treatment (such as chemotherapy or combined immunotherapy) in the past
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Patients planning to receive topotecan : previously received 1/2 line chemotherapy or combined immunotherapy except for topotecan.
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At least one measurable lesion without radiotherapy that meets RECIST1.1 standard;
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Hemoglobin ≥ 90 g/L ;
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Neutrophil count ≥ 1.5 × 109 /L ;
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Platelet count ≥100 × 109 /L ;
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Creatinine ≤ 15 mg /L or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula ) ;
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Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ;
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Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN or ≤ 5 × ULN (patients with liver metastases) ;
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Albumin ≥ 30 g/L ;
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ECOG PS score:0-2 ;
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Expected survival time ≥ 3 months ;
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Contraception :
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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 ;
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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.
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Understand and sign the informed consent form.
Exclusion Criteria:
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Symptomatic brain metastases that require local radiotherapy or hormone therapy;
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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;
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Uncontrolled ischemic heart disease or congestive heart failure with clinically significance (NYHA Class III or IV) ;
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Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment ;
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Severe active infection;
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Potential inadequate compliance from psychological or other social factors;
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Other uncontrolled severe chronic disease or condition, which considered by Investigator as unsuitable for study participation;
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Known HIV infection, active hepatitis B (defined as HBV DNA positive) and hepatitis C (HCV RNA positive);
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Received radiotherapy within 2 weeks before enrollment ;
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Received cytotoxic or investigational drug treatment within 4 weeks, or non-cytotoxic anti-tumor treatment within 2 weeks before enrollment;
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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;
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Recovery from previous toxicity of anti-tumor treatments to Level 0 or 1 (except for hair loss);
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Allergy to the study drugs or any of their components (Trilaciclib, etoposide, carboplatin, topotecan);
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Unable to act independently by legal restrictions or in the legal sense;
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Women who are pregnant or breastfeeding ;
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Other patients who are considered unsuitable to participate in the study. -
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jilin Cancer Hopspital | Changchun | China |
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.- B02B00801-TRILA-301