Extensive-stage Small-cell Lung CancerPhase 3NCT04902885
Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Small Cell Lung Cancer Patients
A Phase 3 study testing Trilaciclib, carboplatin, etoposide，or Topotecan in people with Extensive-stage Small-cell Lung Cancer, run by Jiangsu Simcere Pharmaceutical Co., Ltd. at 1 site in China.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extensive-stage Small-cell Lung Cancer
- What is being tested?
- Trilaciclib, carboplatin, etoposide，or Topotecan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 95 participants
- Where
- 1 siteChina
- Study dates
- 25 May 2021to 31 Dec 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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:
- Females: All females of childbearing potential must have a negative serum pregnancy test at screening and must use reliable contraception from signing of informed consent through 3 months after the last dose; Male: Female partners of childbearing potential must use reliable contraception from signing the informed consent until 3 months after the last dose;
- Understand and sign informed consent
Who cannot join
- 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;
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- 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;
- Not suitable for participating in this study in the investigator 's opinion.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
This is a multi-center Phase 3 clinical trial with an open-label single-arm safety run-in and PK evaluation part and a randomized double-blind, placebo controlled part in patients with ES-SCLC to evaluate the safety, efficacy, and pharmacokinetic profile of Trilaciclib based on completed clinical studies abroad.
The study consists of 2 parts. The first part, safety run-in and PK evaluation, enrolled approximately 12 patients with extensive-stage small-cell lung cancer, 6 patients each with 1st line ES-SCLC and 2nd/3rd line ES-SCLC to receive Trilaciclib in combination with carboplatin and etoposide (EC regimen) or with topotecan, and based on evaluable data from Cycle 1, evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy (prevention of myelosuppression) of Trilaciclib. The second part is a randomized double-blind, placebo-controlled efficacy validation study, and approximately 80 patients with ES-SCLC will be enrolled in Part II, stratified by 1st line vs 2nd/3rd line ES-SCLC, ECOG PS (0-1 vs 2), and presence vs absence of brain metastases, and randomized in a 1:1 ratio to Trilaciclib and placebo, in which patients with 1st line ES-SCLC receive Trilaciclib/placebo combined with EC regimen (Trilaciclib-EC group and placebo-EC group), and patients with 2nd/3rd line ES-SCLC receive Trilaciclib/placebo combined with topotecan (Trilaciclib-TPT group and placeboTPT group), and the efficacy of Trilaciclib (prevention of myelosuppression) will be evaluated with duration of severe neutropenia (DSN) in Cycle 1 as the primary endpoint. The planned dose of Trilaciclib is 240 mg/m2. If the safety data from the first part of the study suggest that the dose of Trilaciclib needs to be adjusted, 12 additional patients (6 patients each for 1st line ES-SCLC and 2nd/3rd line ESSCLC) will be enrolled in the first part of the study to explore the PK and safety of Trilaciclib 200 mg/m2. The study process includes screening period, treatment period, safety followup and survival follow-up.
The end of the study was defined as death in 75% of subjects, or 12 months after the last subject was enrolled, or the sponsor decided to terminate the study, whichever came first.
- Conditions
- Extensive-stage Small-cell Lung Cancer
- Being tested
- Trilaciclib, carboplatin, etoposide，or Topotecan, placebo, carboplatin, etoposide，or Topotecan
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trilaciclib, carboplatin, etoposide，or TopotecanDrug
Also called Trilaciclib plus chemotherapy
Trilaciclib plus carboplatin, etoposide for first line patients ;Trilaciclib plus Topotecan for second or third line patients
placebo, carboplatin, etoposide，or TopotecanDrug
Also called placebo plus chemotherapy
placebo plus carboplatin, etoposide for first line patients ;placebo plus Topotecan for second or third line patients
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Trilaciclib, carboplatin, etoposide，or Topotecan |
| Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group | Placebo comparator | 42 patients received placebo plus chemotherapy Receives: Drug: placebo, carboplatin, etoposide，or Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle
Secondary outcomes (15)
Occurrence of Severe Neutropenia (SN)
Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period.
Measured: 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)
The occurrence of RBC transfusions was defined as at least 1 cycle with RBC transfusion during the treatment period. For the treatment period, the total number of RBC transfusions was the number of cycles with RBC transfusions.
Measured: 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
Administration of G-CSF was collected with concomitant medications, which were coded using World Health Organization Drug Dictionary (WHO-DD) . A cycle where G-CSF was administered concurrently was identified by comparing the start and stop dates of each administration of G-CSF to the start of cycle and end of cycle. The occurrence of G-CSF administrations was defined as at least 1 cycle with G-CSF administrations during the treatment period. For the treatment period, the total number of G-CSF administrations was the number of cycles with G-CSF administrations.
Measured: 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.
MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelopreservation into a single endpoint. The individual components for MAHE were hospitalization for a hematologic event, febrile neutropenia, death related to treatment, dose delay/reduction due to ANC or platelet counts, prolonged severe neutropenia (duration >5 days), RBC transfusion (actual or eligible) and platelet transfusion (actual or eligible).
Event rate per week， calculated as the total number of events divided by duration of in weeks.
Measured: 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
Occurrence of Grade 3 and 4 hematological toxicities was defined according to CTCAE 5.0 during the treatment period.
Measured: 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
Erythropoiesis Stimulating Agent (ESA) Use Rate
Administration of ESA was collected with concomitant medications, which were coded using WHO-DD . A cycle where an ESA was administered concurrently was identified by comparing the start and stop dates of each administration of an ESA to the start of cycle and end of cycle. The occurrence of ESA administration was at least 1 cycle with an ESA administration during the treatment period. For the treatment period, the total number of ESA administrations was the number of cycles with ESA administrations.
Measured: 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
Recombinant Human Interleukin-11 Use Rate
Administration of interleukin-11 was collected with concomitant medications, which were coded using WHO-DD Version. A cycle where interleukin-11 was administered concurrently was identified by comparing the start and stop dates of each administration of interleukin-11 to the start of cycle and end of cycle. The occurrence of interleukin-11 administration was at least 1 cycle with interleukin-11 administration during the treatment period.
Measured: 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
Thrombopoietin (TPO) Use Rate
Administration of TPO was collected with concomitant medications, which were coded using WHO-DD Version. A cycle where TPO was administered concurrently was identified by comparing the start and stop dates of each administration of TPO to the start of cycle and end of cycle. The occurrence of TPO administration was at least 1 cycle with TPO administration during the treatment period.
Measured: 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 Intravenous or Oral Antibiotic Administration
Administration of intravenous or oral antibiotic was collected with concomitant medications, which were coded using WHO-DD Version. A cycle where intravenous or oral antibiotic was administered concurrently was identified by comparing the start and stop dates of each administration of intravenous or oral antibiotic to the start of cycle and end of cycle. The occurrence of intravenous or oral antibiotic administration was at least 1 cycle with intravenous or oral antibiotic administration during the treatment period.
Measured: 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 Infectious Serious Adverse Events
SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. An infectious SAE was a serious event in the Medical Dictionary for Regulatory Activities (MedDRA) system organ class "infections and infestations" and a preferred term of anal abscess, bacteraemia, bronchitis, candida infection, chronic sinusitis, conjunctivitis, infection, influenza, nasopharyngitis, oral candidiasis, oral herpes, pharyngitis streptococcal, pneumonia, pneumonia bacterial, respiratory tract infection, sepsis, skin infection, upper respiratory tract infection, urinary tract infection, urosepsis or viral upper respiratory tract infection.
Measured: 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 Lung Infection SAEs
SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. A lung infection SAE was a serious event in the MedDRA system organ class "infections and infestations" and a preferred term of bronchitis, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection or viral upper respiratory tract infection.
Measured: 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 Febrile Neutropenia
Each febrile neutropenia event (as defined by Common Terminology Criteria for Adverse Events [CTCAE]) was captured as an AE. The occurrence of febrile neutropenia was defined as at least 1 febrile neutropenia event during the treatment period. For the treatment period, the total number of febrile neutropenia events was the number of febrile neutropenia events with a unique start date.
Measured: 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 Platelet Transfusion
The occurrence of platelet transfusions was defined as at least 1 cycle with platelet transfusion during the treatment period. For the treatment period, the total number of platelet transfusions was the number of cycles with platelet transfusions.
Measured: 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
Objective Tumor Response Rate (ORR)
ORR was performed based on the Response Evaluation Analysis Set (RES). Based on the assessments at each visit, the number and percentage of patients with best response of CR, PR, SD, PD and NE will be summarized by treatment group when CR/PR confirmation is not required and CR/PR confirmation is required, respectively . In particular, SD BOR requires at least 35 days or more after enrollment.ORR was calculated based on the number of patients with best response of CR or PR.
Measured: 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 18 months
Disease Control Rate (DCR)
DCR was performed based on the Response Evaluation Analysis Set (RES). Based on the assessments at each visit, the number and percentage of patients with best response of CR, PR, SD, PD and NE will be summarized by treatment group when CR/PR confirmation is not required and CR/PR confirmation is required, respectively . In particular, SD BOR requires at least 35 days or more after enrollment. DCR was calculated based on the number of patients with best response of CR PR or SD.
Measured: 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 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2021
- Study start25 May 2021
- Primary completion29 Dec 2021
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Extensive-stage Small-cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Jiangsu Simcere Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jiangsu Simcere Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- G1 Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Ying Cheng, Doctor, Principal investigator, Jilin Provincial Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04902885
- Sponsor's protocol ID
- B02B00801-TRILA-301
- Status last verified
- Apr 2024
- First submitted
- 8 May 2021
- Last updated
- 10 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04902885
- Acronym / sponsor ID
- B02B00801-TRILA-301
- Conditions
- Extensive-stage Small-cell Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Jiangsu Simcere Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- G1 Therapeutics, Inc.
- Study start
- 25 May 2021 (actual)
- Primary completion
- 29 Dec 2021 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 26 May 2021 (actual)
- Results
- Posted 10 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multi-center Phase 3 clinical trial with an open-label single-arm safety run-in and PK evaluation part and a randomized double-blind, placebo controlled part in patients with ES-SCLC to evaluate the safety, efficacy, and pharmacokinetic profile of Trilaciclib based on completed clinical studies abroad.
The study consists of 2 parts. The first part, safety run-in and PK evaluation, enrolled approximately 12 patients with extensive-stage small-cell lung cancer, 6 patients each with 1st line ES-SCLC and 2nd/3rd line ES-SCLC to receive Trilaciclib in combination with carboplatin and etoposide (EC regimen) or with topotecan, and based on evaluable data from Cycle 1, evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy (prevention of myelosuppression) of Trilaciclib. The second part is a randomized double-blind, placebo-controlled efficacy validation study, and approximately 80 patients with ES-SCLC will be enrolled in Part II, stratified by 1st line vs 2nd/3rd line ES-SCLC, ECOG PS (0-1 vs 2), and presence vs absence of brain metastases, and randomized in a 1:1 ratio to Trilaciclib and placebo, in which patients with 1st line ES-SCLC receive Trilaciclib/placebo combined with EC regimen (Trilaciclib-EC group and placebo-EC group), and patients with 2nd/3rd line ES-SCLC receive Trilaciclib/placebo combined with topotecan (Trilaciclib-TPT group and placeboTPT group), and the efficacy of Trilaciclib (prevention of myelosuppression) will be evaluated with duration of severe neutropenia (DSN) in Cycle 1 as the primary endpoint. The planned dose of Trilaciclib is 240 mg/m2. If the safety data from the first part of the study suggest that the dose of Trilaciclib needs to be adjusted, 12 additional patients (6 patients each for 1st line ES-SCLC and 2nd/3rd line ESSCLC) will be enrolled in the first part of the study to explore the PK and safety of Trilaciclib 200 mg/m2. The study process includes screening period, treatment period, safety followup and survival follow-up.
The end of the study was defined as death in 75% of subjects, or 12 months after the last subject was enrolled, or the sponsor decided to terminate the study, whichever came first.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part I ( Safety run-in and PK Evaluation); Trilaciclib Group | Active comparator | Drug: Trilaciclib, carboplatin, etoposide，or Topotecan12 patients( 6 patients are first line, 6 patients are second or third line) recieved Trilaciclib(240mg/m^2) plus chemotherapy. |
| Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group | Active comparator | Drug: Trilaciclib, carboplatin, etoposide，or Topotecan41 patients received trilaciclib(240mg/m^2) plus chemotherapy |
| Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group | Placebo comparator | Drug: placebo, carboplatin, etoposide，or Topotecan42 patients received placebo plus chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age ≥ 18 years, male or female;
- Histologically or cytologically confirmed extensive stage small cell lung cancer (ES-SCLC):
- 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;
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trilaciclib, carboplatin, etoposide，or TopotecanAlso: Trilaciclib plus chemotherapyTrilaciclib plus carboplatin, etoposide for first line patients ;Trilaciclib plus Topotecan for second or third line patients | Drug | Part I ( Safety run-in and PK Evaluation); Trilaciclib Group, Part II ( Randomized Double-blind, Placebo-controlled ), Trilaciclib Group |
| placebo, carboplatin, etoposide，or TopotecanAlso: placebo plus chemotherapyplacebo plus carboplatin, etoposide for first line patients ;placebo plus Topotecan for second or third line patients | Drug | Part II ( Randomized Double-blind, Placebo-controlled ), Placebo Group |
Primary outcome
Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity(AUC0-inf) for Part 1
Time frame: Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle
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.
Duration of Severe Neutropenia in Cycle 1 (DSN)
Time frame: At the end of Cycle 1 (each cycle is 21 days)
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.
Maximum Observed Plasma Concentration(Cmax) of Trilaciclib for Part 1
Time frame: Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle
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.
15 secondary outcomes
Occurrence of Severe Neutropenia (SN)
Time frame: 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)
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Erythropoiesis Stimulating Agent (ESA) Use Rate
Time frame: 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
Recombinant Human Interleukin-11 Use Rate
Time frame: 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
Thrombopoietin (TPO) Use Rate
Time frame: 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 Intravenous or Oral Antibiotic Administration
Time frame: 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 Infectious Serious Adverse Events
Time frame: 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 Lung Infection SAEs
Time frame: 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 Febrile Neutropenia
Time frame: 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 Platelet Transfusion
Time frame: 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
Objective Tumor Response Rate (ORR)
Time frame: 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 18 months
Disease Control Rate (DCR)
Time frame: 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 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ying Cheng, Doctor principal investigator
Jilin Provincial Cancer Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trilaciclib, carboplatin, etoposide，or Topotecan in people with Extensive-stage Small-cell Lung Cancer, run by Jiangsu Simcere Pharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity(AUC0-inf) for Part 1 (time frame: Day1 and Day 3( or Day 5) of Cycle 1 for a 21-day cycle). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.