Trilaciclib (G1T28) in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy

NCT ID: NCT02514447

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-05
• Study Completion Date: 2021-10-04

Brief Summary

This was a study to investigate the potential clinical benefit of trilaciclib (G1T28), a Cyclin Dependent Kinase (CDK) 4/6 inhibitor, in preserving the bone marrow and the immune system, in order to decrease chemotherapy-induced myelosuppression and improve anti-tumor efficacy when administered prior to topotecan in patients previously treated for extensive-stage SCLC.

The study consisted of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of first dose with study treatment and completes at the Post-Treatment Visit.

Detailed Description

Overall, up to 130 patients were planned to be enrolled in the study. In Part 1, approximately 40 patients were planned to be enrolled, assuming 9 to 10 cohorts. Part 1 was open-label, and no randomization or blinding was required. In Part 2A, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/m2) and topotecan (0.75 mg/m2) or placebo and topotecan (1.5 mg/m2). In Part 2B, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/mg2) and topotecan (1.5 mg/m2) or placebo and topotecan (1.5 mg/m2).

Patients who received placebo in Part 2A and Part 2B were to be combined into a single placebo group for the analysis to compare with trilaciclib+topotecan 1.5 mg/m2 with placebo + topotecan 1.5 mg/m2 (proximately 30 per treatment group).

The sample size calculation was to demonstrate the superiority of trilaciclib + topotecan 1.5 mg/m2 over placebo + topotecan 1.5 mg/m2 with respect to at least 1 of the primary endpoints. The overall type I error rate was 1-sided 0.10. Using the most conservative Bonferroni procedure for the 2 primary endpoints, a 1-sided individual type I error rate 0.10/2=0.05 was assigned to each outcome variable (DSN in Cycle 1 and occurrence of SN) in the sample size calculation. Assuming a common standard deviation of 2.5, a difference in the duration of SN in Cycle 1 of at least 2 days between the treatment groups, a sample size of 28 per arm was required to have 90% power to detect the assumed treatment effect. For occurrence of SN, assuming the event rate was 45% for placebo group, to detect an absolute reduction of 37% by trilaciclib group with 90% power would require a sample size of at least 29 per arm. Thus, 30 per arm was needed to ensure 90% power to detect assumed treatment effect for DSN in Cycle 1 and occurrence of SN. All calculations were carried out using the POWER procedure in SAS®, Version 9.4 procedure in SAS®, Version 9.4 or higher.

The results from endpoints that were commonly collected at Part 1 and part 2 are presented together in this report.

The posted results represent the final results of Study G1T28-03, a Phase 1b/2a safety and pharmacokinetic (PK) study of trilaciclib (G1T28) in patients with previously treated extensive-stage small cell lung cancer (SCLC) receiving topotecan chemotherapy in the second/third-line (2/3L) setting. The final myelopreservation efficacy results for both parts and exposure for Part 1 are from database lock 1 (data cut-off [DCO] for Primary Completion Date [PCD] 28 September 2018). The final anti-tumor efficacy (BOR, DOR, PFS) for both parts, final overall survival for Part 1 and exposure data from Part 2 are from a second database lock 2 (DCO 31 May 2019) and the final overall survival for Part 2 and safety (adverse events) are through the end of the study on October 4, 2021 which resulted in the final database lock (DCO 01 Nov 2021).

The maximum time frames provided reflect the time from when the first patient could be evaluated for an endpoint (ie. date of first dose of first patient) to the time when the data from both parts presented for that endpoint was considered final.

Conditions

Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b

Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²).

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a

Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b

Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²).

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1

Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²).

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1

Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²).

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1

Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1

Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1

Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²).

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1

Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle.

Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Interventions

Trilaciclib

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Other Intervention Names

G1T28; CDK 4/6 inhibitor

Eligibility Criteria

Inclusion Criteria

• Male or female subjects aged ≥18 years
• Confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
• Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy
• At least 1 target lesion that is measurable by RECIST, Version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
• Adequate organ function

Exclusion Criteria

• Presence of brain metastases requiring immediate treatment with radiation therapy or steroids.
• Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure
• Known history of stroke or cerebrovascular accident within 6 months prior to enrollment
• Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol
• Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment or previous radiotherapy to the target lesion sites
• Receipt of any systemic chemotherapy regimen within 4 weeks prior to enrollment or a noncytotoxic investigational medication within 2 weeks prior to enrollment
• History of topotecan treatment for SCLC

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

G1 Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Contact

Role: STUDY_DIRECTOR

G1 Therapeutics, Inc.

Locations

Genesis Cancer Center

Hot Springs, Arkansas, United States

Highlands Oncology Group

Rogers, Arkansas, United States

Compassionate Cancer Care Medical Group, Inc.

Corona, California, United States

Sutter Medical Group

Sacramento, California, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Memorial Hospital - University of Colorado Health

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

University of Colorado Health, Oncology Clinical Research Northern Region

Fort Collins, Colorado, United States

Florida Cancer Specialists - South

Fort Myers, Florida, United States

Florida Cancer Specialists - North

Tavares, Florida, United States

University Cancer and Blood Center, LLC

Athens, Georgia, United States

Emory University

Atlanta, Georgia, United States

Northside Hospital - Georgia Cancer Specialists

Atlanta, Georgia, United States

Saint Luke's Cancer Institute

Kansas City, Missouri, United States

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

North Shore Hematology Oncology Associates PC

East Setauket, New York, United States

Regional Medical Oncology Center

Wilson, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

Oklahoma University - Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Guthrie Medical Group, PC

Sayre, Pennsylvania, United States

AnMed Health

Anderson, South Carolina, United States

Greenville Health System

Greenville, South Carolina, United States

Gibbs Cancer Center

Spartanburg, South Carolina, United States

Hanna Cancer Associates - University of Tennessee

Knoxville, Tennessee, United States

Meharry Medical College

Nashville, Tennessee, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Texas Oncology- Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

M.D. Anderson

Houston, Texas, United States

Millennium Oncology

Houston, Texas, United States

Southwest Cancer Center

Lubbock, Texas, United States

Texas Oncology

Tyler, Texas, United States

The University of Texas Health Science Center at Tyler

Tyler, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Northwest Cancer Specialists, P.C.

Vancouver, Washington, United States

AZ Klina

Brasschaat, , Belgium

University Clinical Centre Banja Luka

Banja Luka, , Bosnia and Herzegovina

University Clinical Centre Sarajevo

Sarajevo, , Bosnia and Herzegovina

Clinical Hospital Centre Osijek

Osijek, , Croatia

University Clinical Hospital Centre " Sestre Milosrdnice"

Zagreb, , Croatia

University Hospital Centre Zagreb, Clinic For Pulmonary Diseases Jordanovac

Zagreb, , Croatia

University Clinic of Radiotherapy and Oncology Skopje

Skopje, , North Macedonia

Clinic for Pulmology, Clinical Centre of Serbia

Belgrade, , Serbia

Clinical Hospital Centre Bezanijska Kosa

Belgrade, , Serbia

Oncology and Radiology Institute of Serbia

Belgrade, , Serbia

Institute for Pulmonary Diseases of Vojvodina Clinic for Thoracic Oncology

Kamenitz, , Serbia

Clinical Center Nis, Clinic for Lung Diseases

Niš, , Serbia

VOU Department of Radiotherapy and Oncology

Košice, , Slovakia

POKO POPRAD, s.r.o.

Poprad, , Slovakia

University Clinic of Respiratory and Allergic Diseases Golnik

Golnik, , Slovenia

Countries

United States; Belgium; Bosnia and Herzegovina; Croatia; North Macedonia; Serbia; Slovakia; Slovenia

References

Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, Hanna WT, Aljumaily R, Owonikoko TK, Verhoeven D, Xiao J, Morris SR, Antal JM, Hussein MA. Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study. Adv Ther. 2021 Jan;38(1):350-365. doi: 10.1007/s12325-020-01538-0. Epub 2020 Oct 29.

Reference Type: RESULT

PMID: 33123968 (View on PubMed)

Li C, Horton JK, Sale M, Curd L, Goti V, Tao W, Beelen A. Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer. Clin Drug Investig. 2022 Aug;42(8):679-692. doi: 10.1007/s40261-022-01179-x. Epub 2022 Jul 16.

Reference Type: DERIVED

PMID: 35842567 (View on PubMed)

Hussein M, Maglakelidze M, Richards DA, Sabatini M, Gersten TA, Lerro K, Sinielnikov I, Spira A, Pritchett Y, Antal JM, Malik R, Beck JT. Myeloprotective Effects of Trilaciclib Among Patients with Small Cell Lung Cancer at Increased Risk of Chemotherapy-Induced Myelosuppression: Pooled Results from Three Phase 2, Randomized, Double-Blind, Placebo-Controlled Studies. Cancer Manag Res. 2021 Aug 9;13:6207-6218. doi: 10.2147/CMAR.S313045. eCollection 2021.

Reference Type: DERIVED

PMID: 34408488 (View on PubMed)

Ferrarotto R, Anderson I, Medgyasszay B, Garcia-Campelo MR, Edenfield W, Feinstein TM, Johnson JM, Kalmadi S, Lammers PE, Sanchez-Hernandez A, Pritchett Y, Morris SR, Malik RK, Csoszi T. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials. Cancer Med. 2021 Sep;10(17):5748-5756. doi: 10.1002/cam4.4089. Epub 2021 Aug 18.

Reference Type: DERIVED

PMID: 34405547 (View on PubMed)

Li C, Hart L, Owonikoko TK, Aljumaily R, Rocha Lima CM, Conkling PR, Webb RT, Jotte RM, Schuster S, Edenfield WJ, Smith DA, Sale M, Roberts PJ, Malik RK, Sorrentino JA. Trilaciclib dose selection: an integrated pharmacokinetic and pharmacodynamic analysis of preclinical data and Phase Ib/IIa studies in patients with extensive-stage small cell lung cancer. Cancer Chemother Pharmacol. 2021 May;87(5):689-700. doi: 10.1007/s00280-021-04239-9. Epub 2021 Feb 17.

Reference Type: DERIVED

PMID: 33595690 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Region 1

View Document

Document Type: Statistical Analysis Plan: Region 2

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/33123968/

Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study

Other Identifiers

2016-004611-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

G1T28-03

Identifier Type: -

Identifier Source: org_study_id