This is a multicenter, randomized, double-blind, placebo-controlled study to assess whether trilaciclib administered prior to topotecan is non-inferior to placebo administered prior to topotecan with regard to overall survival.
The study will include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. Patients randomized in this study will receive trilaciclib/placebo + topotecan 1.5 mg/m2 until disease progression, unacceptable toxicity, withdrawal of consent, Investigator decision to discontinue treatment, or the end of the trial, whichever comes first. Trilaciclib was approved by the United States (US) Food and Drug Administration (FDA) as a treatment to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for ES-SCLC. As a post-marketing requirement, the FDA asked the Sponsor to conduct a study in patients with ES-SCLC undergoing chemotherapy to evaluate survival and disease progression following trilaciclib administration in patients treated with a platinum/etoposide-containing regimen or topotecan-containing regimen with at least 2 years of follow-up. This study is designed to fulfill this requirement.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
302
Participants will receive intravenous trilaciclib infusion
Participants will receive intravenous placebo infusion
Participants will receive intravenous topotecan infusion
Hospital
Seville, Spain
RECRUITINGOverall survival (OS)
To assess the effect of trilaciclib on OS compared with placebo in patients receiving topotecan
Time frame: From date of randomization until date of death due to any cause for those who died; or date of last contact known as alive for those who survived in the study (censored cases), assessed up to 52 months
Anti-tumor efficacy
To assess the effect of trilaciclib on Progression Free Survival (PFS) compared with placebo in patients receiving Topotecan
Time frame: From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first, assessed up to 52 months
Anti-tumor efficacy
To assess the effect of trilaciclib on objective response rate (ORR) compared with placebo in patients receiving Topotecan
Time frame: From date of randomization until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, assessed up to 52 months
Anti-tumor efficacy
To assess the effect of trilaciclib on duration of response (DOR) compared with placebo in patients receiving Topotecan
Time frame: From date of first objective response of complete response (CR) or partial response (PR) and the first date that progressive disease is objectively documented or death, whichever comes first, assessed up to 52 months
Neutrophil-related myeloprotection efficacy
Duration of severe (CTCAE Grade 4) neutropenia in Cycle 1
Time frame: From date of randomization until end of cycle 1 (each cycle is 21 days)
Neutrophil-related myeloprotection efficacy
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Occurrence of severe (CTCAE Grade 4) neutropenia and febrile neutropenia AEs
Time frame: From date of randomization until end of treatment, assessed up to 52 months
Neutrophil-related myeloprotection efficacy
Occurrence of G-CSF administration
Time frame: From date of randomization until end of treatment, assessed up to 52 months
RBC related myeloprotection efficacy
Occurrence of CTCAE Grade 3 or 4 decreased hemoglobin laboratory values and ESA administration
Time frame: From date of randomization until end of treatment, assessed up to 52 months
RBC related myeloprotection efficacy
RBC transfusions on or after Week 5 (occurrence)
Time frame: From date of randomization until end of Week 5
RBC related myeloprotection efficacy
RBC transfusions on or after Week 5 (number of transfusions)
Time frame: From date of randomization until end of Week 5
Platelet related myeloprotection efficacy
Occurrence of CTCAE Grade 3 or 4 decreased platelet count laboratory values and Platelet transfusions (occurrence)
Time frame: From date of randomization until end of treatment, assessed up to 52 months
Platelet related myeloprotection efficacy
Occurrence of CTCAE Grade 3 or 4 decreased platelet count laboratory values and Platelet transfusions (number of transfusions)
Time frame: From date of randomization until end of treatment, assessed up to 52 months
Myeloprotection efficacy
Occurrence of hospitalizations due to chemotherapy-induced myelosuppression
Time frame: From date of randomization until end of treatment, assessed up to 52 months
Myeloprotection efficacy
Number of hospitalizations due to chemotherapy-induced myelosuppression
Time frame: From date of randomization until end of treatment, assessed up to 52 months
Chemotherapy dosing
To assess the effects of trilaciclib on chemotherapy dosing (delays) compared with placebo when administered prior to topotecan.
Time frame: From the date of randomization until end of treatment, assessed up to 52 months
Chemotherapy dosing
To assess the effects of trilaciclib on chemotherapy dosing (reductions) compared with placebo when administered prior to topotecan.
Time frame: From the date of randomization until end of treatment, assessed up to 52 months
Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE
To assess the effects of trilaciclib administered prior to topotecan compared with placebo administered prior to topotecan on occurrence and severity of adverse events by CTCAE, study treatment discontinuation due to adverse events, and trilaciclib adverse events of special interest
Time frame: From the date of randomization until end of treatment, assessed up to 52 months