Trilaciclib vs Placebo in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) Receiving Topotecan

Sponsor

G1 Therapeutics, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05874401

Collaborator

(none)

302

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Extensive-stage Small-cell Lung Cancer	Drug: Trilaciclib Drug: Placebo Drug: Topotecan	Phase 4

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

302 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled Study of Trilaciclib vs Placebo in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) Receiving Topotecan Chemotherapy

Anticipated Study Start Date :

Jun 30, 2023

Anticipated Primary Completion Date :

Jul 30, 2027

Anticipated Study Completion Date :

Jul 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² Patients randomized 1:1 to trilaciclib. Patients receive trilaciclib (240 mg/m²) administered once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients receive topotecan (1.5 mg/m²)	Drug: Trilaciclib Participants will receive intravenous trilaciclib infusion Other Names: G1T28 CDK 4/6 inhibitor cyclin-dependent kinase 4/6 inhibitor Drug: Topotecan Participants will receive intravenous topotecan infusion Other Names: Hycamtin
Placebo Comparator: Placebo + Topotecan 1.5 mg/m² Patients are randomized 1:1 to placebo. Patients receive placebo administered once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients receive topotecan (1.5 mg/m²).	Drug: Placebo Participants will receive intravenous placebo infusion Drug: Topotecan Participants will receive intravenous topotecan infusion Other Names: Hycamtin

Arm

Intervention/Treatment

Experimental: Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m²

Patients randomized 1:1 to trilaciclib. Patients receive trilaciclib (240 mg/m²) administered once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients receive topotecan (1.5 mg/m²)

Drug: Trilaciclib

Participants will receive intravenous trilaciclib infusion

Other Names:

G1T28

CDK 4/6 inhibitor

cyclin-dependent kinase 4/6 inhibitor

Drug: Topotecan

Participants will receive intravenous topotecan infusion

Other Names:

Hycamtin

Placebo Comparator: Placebo + Topotecan 1.5 mg/m²

Patients are randomized 1:1 to placebo. Patients receive placebo administered once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients receive topotecan (1.5 mg/m²).

Drug: Placebo

Participants will receive intravenous placebo infusion

Drug: Topotecan

Participants will receive intravenous topotecan infusion

Other Names:

Hycamtin

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [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]
To assess the effect of trilaciclib on OS compared with placebo in patients receiving topotecan

Secondary Outcome Measures

Anti-tumor efficacy [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]
To assess the effect of trilaciclib on Progression Free Survival (PFS) compared with placebo in patients receiving Topotecan
Anti-tumor efficacy [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]
To assess the effect of trilaciclib on objective response rate (ORR) compared with placebo in patients receiving Topotecan
Anti-tumor efficacy [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]
To assess the effect of trilaciclib on duration of response (DOR) compared with placebo in patients receiving Topotecan
Neutrophil-related myeloprotection efficacy [From date of randomization until end of cycle 1 (each cycle is 21 days)]
Duration of severe (CTCAE Grade 4) neutropenia in Cycle 1
Neutrophil-related myeloprotection efficacy [From date of randomization until end of treatment, assessed up to 52 months]
Occurrence of severe (CTCAE Grade 4) neutropenia and febrile neutropenia AEs
Neutrophil-related myeloprotection efficacy [From date of randomization until end of treatment, assessed up to 52 months]
Occurrence of G-CSF administration
RBC related myeloprotection efficacy [From date of randomization until end of treatment, assessed up to 52 months]
Occurrence of CTCAE Grade 3 or 4 decreased hemoglobin laboratory values and ESA administration
RBC related myeloprotection efficacy [From date of randomization until end of Week 5]
RBC transfusions on or after Week 5 (occurrence)
RBC related myeloprotection efficacy [From date of randomization until end of Week 5]
RBC transfusions on or after Week 5 (number of transfusions)
Platelet related myeloprotection efficacy [From date of randomization until end of treatment, assessed up to 52 months]
Occurrence of CTCAE Grade 3 or 4 decreased platelet count laboratory values and Platelet transfusions (occurrence)
Platelet related myeloprotection efficacy [From date of randomization until end of treatment, assessed up to 52 months]
Occurrence of CTCAE Grade 3 or 4 decreased platelet count laboratory values and Platelet transfusions (number of transfusions)
Myeloprotection efficacy [From date of randomization until end of treatment, assessed up to 52 months]
Occurrence of hospitalizations due to chemotherapy-induced myelosuppression
Myeloprotection efficacy [From date of randomization until end of treatment, assessed up to 52 months]
Number of hospitalizations due to chemotherapy-induced myelosuppression
Chemotherapy dosing [From the date of randomization until end of treatment, assessed up to 52 months]
To assess the effects of trilaciclib on chemotherapy dosing (delays) compared with placebo when administered prior to topotecan.
Chemotherapy dosing [From the date of randomization until end of treatment, assessed up to 52 months]
To assess the effects of trilaciclib on chemotherapy dosing (reductions) compared with placebo when administered prior to topotecan.
Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE [From the date of randomization until end of treatment, assessed up to 52 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

ES-SCLC with confirmed diagnosis of SCLC by histology or cytology
Progression during or after prior first or second line chemotherapy. First-line regimen must have been a platinum-containing combination.
Measurable or evaluable disease as defined by RECIST v1.1

Exclusion Criteria:

History of topotecan (or other topoisomerase I inhibitor) or trilaciclib treatment for SCLC
Any chemotherapy, immunotherapy, biologic, investigational, or hormonal therapy for cancer treatment within 3 weeks, except for adjuvant hormonal therapy for breast cancer and prostate cancer
Presence of brain metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids
Radiotherapy within 2 weeks
History of ILD/pneumonitis
History of other malignancies, except for curatively treated solid tumors with no evidence of disease for ≥ 2 years or other NCS cancers