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

• ClinicalTrials.gov Identifier: NCT02514447
• Recruitment Status: Terminated
• First Posted: August 3, 2015
• Results First Posted: June 9, 2022
• Last Update Posted: June 9, 2022
• Sponsor: G1 Therapeutics, Inc.
• Information provided by (Responsible Party): G1 Therapeutics, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Small Cell Lung Cancer	Drug: Trilaciclib; Drug: Placebo; Drug: Topotecan	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients With Previously Treated Extensive Stage Small Cell Lung Cancer (SCLC) Receiving Topotecan Chemotherapy
• Actual Study Start Date: October 5, 2015
• Actual Primary Completion Date: September 28, 2018
• Actual Study Completion Date: October 4, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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).	Drug: Placebo; Drug: Topotecan
Experimental: 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).	Drug: Trilaciclib; Other Names: G1T28; CDK 4/6 inhibitor; Drug: Topotecan
Experimental: 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).	Drug: Trilaciclib; Other Names: G1T28; CDK 4/6 inhibitor; Drug: Topotecan
Experimental: 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).	Drug: Trilaciclib; Other Names: G1T28; CDK 4/6 inhibitor; Drug: Topotecan
Experimental: 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).	Drug: Trilaciclib; Other Names: G1T28; CDK 4/6 inhibitor; Drug: Topotecan
Experimental: 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).	Drug: Trilaciclib; Other Names: G1T28; CDK 4/6 inhibitor; Drug: Topotecan
Experimental: 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).	Drug: Trilaciclib; Other Names: G1T28; CDK 4/6 inhibitor; Drug: Topotecan
Experimental: 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).	Drug: Trilaciclib; Other Names: G1T28; CDK 4/6 inhibitor; Drug: Topotecan
Experimental: 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).	Drug: Trilaciclib; Other Names: G1T28; CDK 4/6 inhibitor; Drug: Topotecan

Outcome Measures

Primary Outcome Measures :

1. Duration of Severe (Grade 4) Neutropenia in Cycle 1 [ Time Frame: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days) ]
   Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: (1) occurred after the ANC value of <0.5 × 10^9/L and (2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. DSN is set to 0 for patients who did not experience SN in a cycle, including those who were randomized but never treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.
2. Occurrence of Severe (Grade 4) Neutropenia [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
   Number of Participants with severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value <0.5 × 10^9/L during the Treatment Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
3. Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 [ Time Frame: Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1) to the end of Cycle 1, each cycle = 21 days) ]

   The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including:

   • Absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting for ≥ 7 days
   • ≥ Grade 3 neutropenic infection/febrile neutropenia
   • Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia with bleeding
   • Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10^9/L and platelet count ≥ 100 × 10^9/L; a delay of up to 1 week from the scheduled start of Cycle 2 is allowed for recovery of ANC and platelet count, and is not considered a DLT
   • ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for > 72 hours)

Secondary Outcome Measures :

1. Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan [ Time Frame: Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose. ]
   Maximum concentration (Cmax) of trilaciclib (G1T28) when administered with topotecan
2. Progression Free Survival (PFS) [ Time Frame: From date of first dose of study drug (Part 1)/randomization (Part 2), until date of documented disease progression or death due to any cause (evaluated up to a maximum of 1335 days). ]

   Median time (months) and 95% CI from date of first dose of study drug/randomization until date of documented disease progression or death due to any cause.

   Investigators followed the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines for tumor assessments to determine progression. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

3. Overall Survival (OS) [ Time Frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2220 days). ]
   Median time (months) and 95% CI from date of first dose date of study drug/randomization until date of death. Patients who do not die during the study will be censored at the date last known to be alive.
4. Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
   The weekly event rate of Major Adverse Hematologic Events (MAHE) events
5. Tumor Response Based on RECIST, Version 1.1 [ Time Frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days). ]

   The percentage of patients who fall into each category of Best overall response (BOR) as defined by RECIST, Version 1.1.

   Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.

   Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions.

   Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

   When no imaging/measurement is done, the patient is not evaluable (NE); and if only a subset of lesion measurements are made, usually the case is also considered NE.

6. Occurrence of RBC Transfusions [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1056 days). ]
   Percentage of patients requiring a RBC transfusion on/after week 5
7. Need for Treatment With Hematopoietic Growth Factors [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
   Percentage of patients requiring G-CSF administration.
8. Chemotherapy Cycles and Modifications Overall [ Time Frame: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days). ]
   Average exposure and cycle modifications in chemotherapy (topotecan)
9. Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) [ Time Frame: Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose. ]
   Maximum concentration (Cmax) of topotecan when administered with trilaciclib (G1T28)
10. Duration of Response (DOR) [ Time Frame: From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days). ]
    The median months and 95% CIs of duration of response.
11. Occurrence of Intravenous (IV) Antibiotic Use [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    Percentage of patients requiring systemic/IV antibiotics
12. Occurrence of Platelet Transfusions [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    Percentage of patients requiring a platelet transfusion
13. Occurrence of Febrile Neutropenia Adverse Events [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    Percentage of patients who experience febrile neutropenia adverse events
14. Occurrence of Infection Serious Adverse Events (SAEs) [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations
15. Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations and falls into a preferred term (PT) categorized as a pulmonary infection custom MedDRA query (CMQ)
16. Dose Reductions in Chemotherapy (Topotecan) [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    Overall event rate of dose reductions in chemotherapy (topotecan)
17. Occurrence of Grade 3 and 4 Hematologic Toxicities [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    The count of patients with any hematologic lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug). Labs include: Hemoglobin (HGB), hematocrit, white blood cell (WBC), platelet counts, ANC, ALC, Monocyte Absolute, Basophil Absolute, and Eosinophil Absolute.
18. Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    The count of patients with any platelet lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug).
19. Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations [ Time Frame: During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). ]
    The count of patients who received any ESA administration.
20. Chemotherapy Exposure [ Time Frame: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days). ]
    Average duration of exposure to chemotherapy (topotecan) in days.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key 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

Key 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

Contacts and Locations

Locations

United States, Arkansas

Genesis Cancer Center

Hot Springs, Arkansas, United States, 71913

Highlands Oncology Group

Rogers, Arkansas, United States, 72758

United States, California

Compassionate Cancer Care Medical Group, Inc.

Corona, California, United States, 92879

Sutter Medical Group

Sacramento, California, United States, 95816

The Oncology Institute of Hope and Innovation

Whittier, California, United States, 90603

United States, Colorado

Memorial Hospital - University of Colorado Health

Colorado Springs, Colorado, United States, 80909

Rocky Mountain Cancer Centers

Denver, Colorado, United States, 80218

University of Colorado Health, Oncology Clinical Research Northern Region

Fort Collins, Colorado, United States, 80528

United States, Florida

Florida Cancer Specialists - South

Fort Myers, Florida, United States, 33916

Florida Cancer Specialists - North

Tavares, Florida, United States, 32778

United States, Georgia

University Cancer and Blood Center, LLC

Athens, Georgia, United States, 30607

Emory University

Atlanta, Georgia, United States, 30322

Northside Hospital - Georgia Cancer Specialists

Atlanta, Georgia, United States, 30341

United States, Missouri

Saint Luke's Cancer Institute

Kansas City, Missouri, United States, 64111

United States, New Hampshire

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States, 03756

United States, New York

North Shore Hematology Oncology Associates PC

East Setauket, New York, United States, 11733

United States, North Carolina

Regional Medical Oncology Center

Wilson, North Carolina, United States, 27893

United States, Ohio

Gabrail Cancer Center

Canton, Ohio, United States, 44718

United States, Oklahoma

Oklahoma University - Peggy and Charles Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73117

United States, Pennsylvania

Guthrie Medical Group, PC

Sayre, Pennsylvania, United States, 18840

United States, South Carolina

AnMed Health

Anderson, South Carolina, United States, 29621

Greenville Health System

Greenville, South Carolina, United States, 29605

Gibbs Cancer Center

Spartanburg, South Carolina, United States, 29303

United States, Tennessee

Hanna Cancer Associates - University of Tennessee

Knoxville, Tennessee, United States, 37920

Meharry Medical College

Nashville, Tennessee, United States, 37208

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Oncology- Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States, 75246

M.D. Anderson

Houston, Texas, United States, 77030

Millennium Oncology

Houston, Texas, United States, 77090

Southwest Cancer Center

Lubbock, Texas, United States, 79415

Texas Oncology

Tyler, Texas, United States, 75702

The University of Texas Health Science Center at Tyler

Tyler, Texas, United States, 75708

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

Virginia Oncology Associates

Norfolk, Virginia, United States, 23502

United States, Washington

Northwest Cancer Specialists, P.C.

Vancouver, Washington, United States, 98684

Belgium

AZ Klina

Brasschaat, Belgium, 2930

Bosnia and Herzegovina

University Clinical Centre Banja Luka

Banja Luka, Bosnia and Herzegovina, 78000

University Clinical Centre Sarajevo

Sarajevo, Bosnia and Herzegovina, 71000

Croatia

Clinical Hospital Centre Osijek

Osijek, Croatia, 31000

University Clinical Hospital Centre " Sestre Milosrdnice"

Zagreb, Croatia, 10000

University Hospital Centre Zagreb, Clinic For Pulmonary Diseases Jordanovac

Zagreb, Croatia, 10000

North Macedonia

University Clinic of Radiotherapy and Oncology Skopje

Skopje, North Macedonia, 1000

Serbia

Clinic for Pulmology, Clinical Centre of Serbia

Belgrade, Serbia, 11000

Clinical Hospital Centre Bezanijska Kosa

Belgrade, Serbia, 11000

Oncology and Radiology Institute of Serbia

Belgrade, Serbia, 11000

Clinical Center Nis, Clinic for Lung Diseases

Nis, Serbia, 18204

Institute for Pulmonary Diseases of Vojvodina Clinic for Thoracic Oncology

Sremska Kamenica, Serbia, 21204

Slovakia

VOU Department of Radiotherapy and Oncology

Kosice, Slovakia, 04191

POKO POPRAD, s.r.o.

Poprad, Slovakia, 05801

Slovenia

University Clinic of Respiratory and Allergic Diseases Golnik

Golnik, Slovenia

Sponsors and Collaborators

G1 Therapeutics, Inc.

Investigators

• Study Director: Clinical Contact; G1 Therapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by G1 Therapeutics, Inc.:

Study Protocol  [PDF] June 27, 2018

Statistical Analysis Plan: Region 1  [PDF] December 5, 2018

Statistical Analysis Plan: Region 2  [PDF] December 5, 2018

More Information

Additional Information:

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

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

• Responsible Party: G1 Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02514447
• Other Study ID Numbers: G1T28-03; 2016-004611-13 ( EudraCT Number )
• First Posted: August 3, 2015
• Results First Posted: June 9, 2022
• Last Update Posted: June 9, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by G1 Therapeutics, Inc.:

SCLC; CDK4/6 Inhibitor

Additional relevant MeSH terms:

Lung Neoplasms; Small Cell Lung Carcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Topotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents