Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Small Cell Lung Cancer Patients

NCT04902885 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: B02B00801-TRILA-301
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

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.

Conditions

Extensive-stage Small-cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity(AUC0-inf) for Part 1

  AUC0-inf of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.

  Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle

• Duration of Severe Neutropenia in Cycle 1 (DSN)

  DSN in Cycle 1 was defined as the number of days from the date of the first ANC value \< 0.5 x 10\^9/L in Cycle 1 to the date of the first ANC value ≥ 0.5 x 10\^9/L. The date of the first ANC value ≥ 0.5 x 10\^9/L should meet the following requirements: (1) occurred after the ANC value was \< 0.5 x 10\^9/L, and (2) there were no other ANC values \< 0.5 x 10\^9/L between this date and the end of Cycle 1 (otherwise, if this patient entered Cycle 2, it was counted as Day 1 of Cycle 2). DSN in Cycle 1 was scored as 0 if the patient did not experience any SN during Cycle 1.

  At the end of Cycle 1 (each cycle is 21 days)

• Maximum Observed Plasma Concentration(Cmax) of Trilaciclib for Part 1

  Cmax of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. For estimation of Cmax, a concentration that was below the limit of quantification (BLQ) was assigned a value of zero if it occurred in a profile before the first measurable concentration. If a BLQ value occurred after a measurable concentration in a profile, and was followed by a value above the lower limit of quantification, then the BLQ was treated as missing data. If a BLQ value occurred at the end of the collection interval (after the last quantifiable concentration) it was treated as missing data. If two BLQ values occurred in succession after Cmax, the profile was deemed to have terminated at the first BLQ value and any subsequent concentrations were omitted.

  Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle

Secondary Outcomes (15)

• Occurrence of Severe Neutropenia (SN)

  From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

• Occurrence of Red Blood Cell Transfusion (on/After Week 5)

  From week 5 to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

• Granulocyte Colony Stimulating Factor (G-CSF) Use Rate

  From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

• Composite Endpoints-major Hematologic AEs (Anyone of the Followings): All-cause Hospitalization; All-cause Dose Reductions; Febrile Neutropenia; SN Prolongation (Lasting > 5 Days); Red Blood Cell (RBC) Transfusions Were Performed on/After Week 5.

  From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

• Occurrence of Grade 3 and 4 Hematological Toxicities

  From date of randomization , 21 day treatment cycle to the end of the treatment until (if earlier) disease progression, start of subsequent anticancer treatment, withdrawal of informed consent, or death, acessed up to a maximum of 12 months

Study Arms (3)

Part I ( Safety run-in and PK Evaluation); Trilaciclib Group

ACTIVE COMPARATOR

12 patients( 6 patients are first line, 6 patients are second or third line) recieved Trilaciclib(240mg/m\^2) plus chemotherapy.

Drug: Trilaciclib, carboplatin, etoposide，or Topotecan

Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group

ACTIVE COMPARATOR

41 patients received trilaciclib(240mg/m\^2) plus chemotherapy

Drug: Trilaciclib, carboplatin, etoposide，or Topotecan

Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group

PLACEBO COMPARATOR

42 patients received placebo plus chemotherapy

Drug: placebo, carboplatin, etoposide，or Topotecan

Interventions

Trilaciclib, carboplatin, etoposide，or Topotecan DRUG

Trilaciclib plus carboplatin, etoposide for first line patients ;Trilaciclib plus Topotecan for second or third line patients

Also known as: Trilaciclib plus chemotherapy

Part I ( Safety run-in and PK Evaluation); Trilaciclib Group; Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group

placebo, carboplatin, etoposide，or Topotecan DRUG

placebo plus carboplatin, etoposide for first line patients ;placebo plus Topotecan for second or third line patients

Also known as: placebo plus chemotherapy

Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years, male or female;
• Histologically or cytologically confirmed extensive stage small cell lung cancer (ES-SCLC):
• Patients scheduled to receive carboplatin plus etoposide regimen: no prior systemic therapy (eg, chemotherapy or combined with immunotherapy);
• Patients scheduled to receive topotecan regimen: previously received 1/2 lines of chemotherapy or combined immunotherapy but not topotecan.
• Presence of at least one radiation-naïve measurable lesion according to RECIST 1.1 criteria;
• Hemoglobin ≥ 90 g/L;
• Neutrophil count ≥ 1.5 × 10\^9/L;
• Platelet count ≥ 100 × 10\^9/L;
• Creatinine ≤ 15 mg/L or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula);
• Total bilirubin ≤ 1.5 × upper 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;
• Contraception:

You may not qualify if:

• Symptomatic brain metastases requiring local radiotherapy or hormonal therapy;
• History of other malignancies, with the following exceptions: (1) clinically cured cutaneous basal cell or squamous cell tumors; (2) cured a) cervical cancer, b) prostate cancer, c) superficial bladder cancer; or (3) other solid tumors with a clinical cure time of more than 3 years;
• Uncontrolled ischemic heart disease or clinically significant congestive heart failure (NYHA Class III or IV);
• Stroke or cardiovascular or cerebrovascular event within 6 months prior to enrollment;
• Severe active infection;
• Psychological or other social factors causing insufficient trial compliance;
• Other uncontrolled serious chronic diseases or conditions that, in the opinion of the investigator, would make participation in the trial inappropriate;
• Known HIV infection, active hepatitis B (defined as positive HBV DNA), and hepatitis C (positive HCV RNA);
• Radiation therapy within 2 weeks prior to enrollment;
• Patients who have received cytotoxic drug therapy or investigational drug therapy within 4 weeks before enrollment, or non-cytotoxic anti-tumor drug therapy within 2 weeks;
• Subjects in the first part of the study should not take strong or moderate inducers of CYP3A4 concomitantly within 4 weeks before taking the study drug, and strong inhibitors of CYP3A4 concomitantly within 2 weeks before taking the study drug;
• Toxicity from prior anticancer therapy has not recovered to Grade 0 or 1 (except alopecia);
• Hypersensitivity to the study drug (Trilaciclib, etoposide, carboplatin, topotecan) or components thereof;
• Persons who are unable to act independently due to legal restriction or legal sense;
• Pregnant or lactating women;

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead
• G1 Therapeutics, Inc.: collaborator

Study Sites (1)

Jilin Cancer Hopspital

Changchun, China

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

trilaciclib; Carboplatin; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Therapeutics

Results Point of Contact

• Title: Study Director
• Organization: Jiangsu Simcere Pharmaceutical Co., Ltd.

simcere@simcere.com

86-025-85566666

Study Officials

• Ying Cheng, Doctor

  Jilin Provincial Cancer Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2021
• First Posted: May 26, 2021
• Study Start: May 25, 2021
• Primary Completion: December 29, 2021
• Study Completion: December 31, 2022
• Last Updated: July 10, 2024
• Results First Posted: July 10, 2024

Record last verified: 2024-04

Locations

CN (1)