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Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)

Primary Purpose

Triple-Negative Breast Neoplasms, Breast Neoplasm, Breast Cancer

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Trilaciclib

Gemcitabine

Carboplatin

About this trial

This is an interventional treatment trial for Triple-Negative Breast Neoplasms focused on measuring Breast Cancer, CDK 4/6 Inhibitor, Triple Negative Breast Cancer, Metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Confirmed diagnosis of hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-negative (locally recurrent or metastatic TNBC) breast cancer
Available TNBC diagnostic tumor tissue (archived tissue allowed)
Evaluable disease
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Adequate organ function
Predicted life expectancy of 3 or more months

Exclusion Criteria:

More than 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC. If > 12 months have elapsed between the date of last adjuvant/neoadjuvant chemotherapy administration and first documented local or distant disease recurrence the therapy will not be considered a line of therapy in the locally recurrent or metastatic TNBC setting.
CNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
Investigational drug within 30 days of first trilaciclib (G1T28) dose
Concurrent radiotherapy, radiotherapy within 14 days of first trilaciclib (G1T28) dose
Cytotoxic chemotherapy within 3 weeks of first trilaciclib (G1T28) dose
Prior hematopoietic stem cell or bone marrow transplantation

Sites / Locations

Arizona Oncology Associates, PC - HOPE
Disney Family Cancer Center
Sharp Clinical Oncology
Innovative Clinical Research Institute
Memorial UC Health
Rocky Mountain Cancer Centers
Florida Cancer Specialists
Florida Cancer Research Institute, LLC.
Florida Cancer Specialists - North (FCS North)
Moffitt Cancer Center
Florida Cancer Specialists - East (FCS East)
Saint Alphonsus Regional Medical Center
Illinois Cancer Specialists
Community Health Network
University of Maryland Greenebaum Comprehensive Cancer Center
The University of Maryland St. Joseph Medical Center
Saint Luke's Cancer Institute
Comprehensive Cancer Centers of Nevada
Levine Cancer Center
Forsyth Memorial Hospital, Novant Health Oncology Specialists
Tennessee Oncology
Tennessee Oncology
Texas Oncology-Dallas Presbyterian Hospital
Texas Oncology, P.A.
Texas Oncology, P.A.
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Texas Oncology-El Paso Cancer Treatment Center Grandview
The Center for Cancer and Blood Disorders
Texas Oncology-San Antonio Northeast
Tyler Hematology-Oncology, PA
Texas Oncology, P.A.
University of Virginia
Virginia Cancer Specialists, PC
Virginia Oncology Associates
Northwest Medical Specialties, PLLC
Antwerp University Hospital (UZA)
University Multiprofile Hospital for Active Treatment
MHAT for Womens Health - Nadezhda OOD
Special Hospital For Active Treatment In Oncology
Multiprofile Hospital for Active Treatment
University Hospital Centre Osijek
General Hospital Varaždin
University Hospital Centre "Sestre milosrdnice"
University Hospital Centre Zagreb
Clinical Hospital Dr. Trifun Panovski
University Clinic of Radiotherapy and Oncology
Special Hospital for Internal Diseases , Oncomed
Clinical Hospital Centre Bezanijska Kosa, Oncology Clinic
Center for Oncology and Radiotherapy, Clinical Centre
Clinical Centre Nis, Clinic of Oncology
Oncology Institute of Vojvodina, Clinic for Internal Oncology
Mammacentrum, Sv.Agáty
Cancer Institute VOU, Rastislavova
University Medical Centre Maribor

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Group 1: Gemcitabine/Carboplatin (Days 1 and 8)

Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8)

Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)

Arm Description

Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square [mg/m^2] and carboplatin area under the curve [AUC] 2) on Days 1 and 8 of 21-day cycle. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).

Participants received IV infusion of trilaciclib 240 mg/m^2 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycle. Trilaciclib was administered prior to chemotherapy.

Participants received IV infusion of trilaciclib 240 mg/m^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day Cycle. Trilaciclib was administered prior to chemotherapy.

Outcomes

Primary Outcome Measures

Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1

DSN was defined as the number of days from the date of the first absolute neutrophil count (ANC) value of less than (<) 0.5 × 10^9 cells/liter (L) observed between Day 1 Cycle 1 and the end of Cycle 1 to the date of the first ANC value greater than or equal to (>=) 0.5 × 10^9/L that met the following: (1) occurred after the ANC value of < 0.5 × 10^9 cells/L and (2) no other ANC values < 0.5 × 10^9 cells/L occurred between this day and the end of Cycle 1. Severe neutropenia (SN) was set to zero for participants who did not experience severe (Grade 4) neutropenia in Cycle 1, including those who were randomized but never treated.

Number of Participants With Severe (Grade 4) Neutropenia (SN)

Number of participants with Grade 4 SN was a binary variable. If a participants had at least 1 ANC value < 0.5 ×10^9/L during the treatment period, the participants was assigned as "yes" to the occurrence of SN. Otherwise, it was "no".

Secondary Outcome Measures

Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

BOR was defined as the best response across all time points (RECIST v1.1). The best overall response was determined once all the data for the participant is known. Each participant has been assigned one of the following categories (RECIST 1.1): complete response (CR): disappearance of all target lesions; partial response (PR): >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; progression disease (PD): >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study); stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD); NE: not evaluable and missing.

Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator

DOR is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Participants who do not experience PD or death was censored at the last tumor assessment date. 95% Confidence Interval (CI) was calculated using the Kaplan-Meier method.

Overall Survival (OS)

Overall survival was defined as the time (months) from date of randomization to the date of death due to any cause. Participants who do not die during the study were censored at the date last known to be alive. The OS was calculated using Kaplan-Meier method.

Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator

PFS was defined as the time (months) from date of randomization until date of documented PD or death due to any cause, whichever comes first. PD: >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study). The PFS was calculated using Kaplan-Meier method.

Relative Dose Intensity of Gemcitabine and Carboplatin

Relative dose intensity was defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity was defined as the cumulative planned dose through the study divided by (number of cycles × 3 weeks). Relative dose intensity (%) was calculated as: for gemcitabine (100 * [Dose intensity (mg/m2/week) / (2000/3 (mg/m2/week)]); for carboplatin (100 * [Dose intensity (AUC/week)/ (4/3) (AUC/week)]) and for trilaciclib (100 * [Dose intensity (mg/m2/week)/ (480 /3 (mg/m2/week)] for Group 2 and 100 * [Dose intensity (mg/m2/week) / (960 /3 (mg/m2/week)] for Group 3).

Duration of Exposure

Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21.

Number of Cycles Participants Received Treatment in Each Treatment Arm

Participants were considered to have started a cycle if they have received at least 1 dose of any study drug.

Cumulative Dose of Gemcitabine

Cumulative dose: Sum of the total doses by cycle administered to a participant in the duration of exposure, i.e. total number of cycles received (milligram per meter square [mg/m^2]).

Cumulative Dose of Carboplatin

Cumulative dose: Sum of the total doses by cycle (AUC) administered to a participant in the duration of exposure, i.e. total number of cycles received (in total prescribed AUC).

Maximum Observed Plasma Concentration (Cmax) of Trilaciclib

The observed peak plasma concentration was determined from the plasma concentration-versus time data.

Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib

AUC0-t was calculated with the linear/log-trapezoidal method, which uses linear interpolation between data points to calculate the AUC. The linear/log-trapezoidal method will be employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method will be used for those arising from decreasing concentrations.

Terminal Elimination Half-Life (t1/2) of Trilaciclib

t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve, the actual body exposure to drug after administration of a dose of the drug ( in mg*h/L).

Maximum Observed Plasma Concentration (Cmax) of Gemcitabine

The observed peak plasma concentration was determined from the plasma concentration-versus time data.

Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine

AUC0-t was calculated with the linear/log-trapezoidal method.

Terminal Elimination Half-Life (t1/2) of Free Carboplatin

Clearance (CL) of of Free Carboplatin

Clearance after intravenous infusion administration was calculated as: CL=Dose/AUC0-inf. AUC0-inf was calculated as: AUC0-inf=AUClast+Clast/lambdaz where Clast is the last quantifiable concentration in the terminal elimination phase.

Volume of Distribution at Steady State (Vss) of Free Carboplatin

Vss was the volume of distribution at steady state of free carboplatin was reported.

Number of Participants With Grade 3 and 4 Hematologic Toxicities

Hematologic toxicities events were defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 hematologic toxicities during the treatment period, the participant was assigned as Yes to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was No. If a participant did not have an event, the value of 0 was assigned to that participant.

Number of Participants With Grade 3 or 4 Thrombocytopenia

Hematologic toxicities events are defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 thrombocytopenia was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 thrombocytopenia during the treatment period, the participant was assigned as "Yes" to the occurrence of Grade 3 and 4 thrombocytopenia; otherwise, it was "No". If a participant did not have an event, the value of 0 was assigned to that participant.

Major Adverse Hematologic Event (MAHE) Rate

MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelosuppression into a single endpoint by summing of the total number of events across a set of pre-specified components.The individual components for MAHE were all-cause hospitalizations, all-cause dose reductions, febrile neutropenia, prolonged severe neutropenia (duration > 5 days), RBC transfusion and platelet transfusion. Event rate for MAHE was calculated as the number of events/durations of treatment period divided by 7 days/1 week.

Number of Participants With Febrile Neutropenia (FN)

The criterion for identifying FN was if the PT was "FEBRILE NEUTROPENIA" the occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.

Number of Participants With Infection SAEs

Number of participants with infection SAEs during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion for identifying the proper infection SAE records was as follows: If the system organ class (SOC) from Medical Dictionary for Regulatory Activities (MedDRA) takes value "INFECTIONS AND INFESTATIONS," and the AE was a serious event.

Number of Participants With Red Blood Cell (RBC) Transfusions On/After Week 5 (Day 35)

Each RBC transfusion with a unique start date on/after 5 weeks on study during the treatment period was defined as a separate event. Occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events >=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.

Number of Participants With Platelet Transfusions

Each platelet transfusion with a unique start date during the treatment period was defined as a separate event. The occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if the total number of events >=1 was observed and No for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.

Number of Participants With Granulocyte Colony-stimulating Factor (G-CSF) Administration

The criterion for selecting proper records is as follows: If the chemical subgroup from the World Health Organization-Drug Dictionary (WHO-DD) takes value "COLONY STIMULATING FACTOR," the medication was classified as G-CSF. The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events >=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.

Number of Participants With Erythropoiesis Stimulating Agent (ESA) Administration

The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events >=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion to select proper records was as follows: If the chemical subgroup from WHO-DD Version September 2017 (i.e., TEXT4 for CODE4) takes value "OTHER ANTIANEMIC PREPARATIONS", the medication was classified as ESAs.

Number of Participants With Intravenous Antibiotics Use

The criteria for identifying an IV antibiotic administration event was (1) if the Therapeutic subgroup from WHO-DD version takes value "ANTIBACTERIALS FOR SYSTEMIC USE", and (2) the route of medication was "intravenous" or the route was "other" with the detailed specification as "IVPB". The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events >=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.

All-cause Dose Reductions, Event Rate (Per Cycle)

Dose reductions were not permitted for trilaciclib. Dose reductions for gemcitabine or carboplatin were collected on the dosing page. No more than 3 dose modifications for toxicity in total were allowed for any participant. All dose reductions were counted as a separate event. Discontinuations of an individual component of the chemotherapy regimen were counted as a dose reduction If the participant continued the other chemotherapy drug as a monotherapy. Event rate was calculated as the total number of cycles with an event divided by the total number of cycles.

Dose Modifications: Number of Participants With Cycle Delays

Dose modifications was summarized for each study drug based on number of cycles received during the treatment period. If the participant was unable to start a new cycle at that next visit, then the cycle is delayed, the reason entered, and the question was asked again at the next visit until the participant either starts a new cycle or discontinues treatment.

Dose Modifications - Number of Participants With Skipped Doses

Dose modifications was summarized for each study drug based on skipped doses not received during the treatment period. Primary reasons for skipped doses included toxicity, investigator decision and administrative reasons (e.g., holidays).

Dose Modifications: Number of Participants With Any Dose Interruptions

Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.

Dose Modifications - Number of Participants With Dose Reductions

Dose (mg/m2) reductions were not permitted for trilaciclib. Dose reductions for carboplatin and gemcitabine were determined by comparing the planned dose on the respective drug administration pages between the current cycle and the previous cycle.

Full Information

NCT ID

NCT02978716

First Posted

November 18, 2016

Last Updated

February 24, 2022

Sponsor

G1 Therapeutics, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02978716

Brief Title

Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)

Official Title

Phase 2 Study of the Safety, Efficacy, and Pharmacokinetics of G1T28 in Patients With Metastatic Triple Negative Breast Cancer Receiving Gemcitabine and Carboplatin Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Terminated

Why Stopped

Primary Analysis and survival follow up completed per protocol. Not stopped due to safety concerns

Study Start Date

February 2, 2017 (Actual)

Primary Completion Date

June 28, 2019 (Actual)

Study Completion Date

February 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

G1 Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This was a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and gemcitabine (GC therapy) for participants with metastatic triple negative breast cancer. The study was an open-label and 102 participants were randomly assigned (1:1:1 fashion) to 1 of the 3 following treatment groups: Group 1: GC therapy (Days 1 and 8 of 21-day cycles) only (n=34) Group 2: GC therapy (Days 1 and 8) plus trilaciclib (G1T28) on Days 1 and 8 of 21-day cycles (n=33) Group 3: GC therapy (Days 2 and 9) plus trilaciclib (G1T28) on Days 1, 2, 8, and 9 of 21-day cycles (n=35) The study included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit.

Detailed Description

The posted results represent the final results of Study G1T28-04, a Phase 2 study of the safety, efficacy and pharmacokinetics of trilaciclib (G1T28) in patients with locally recurrent/metastatic triple negative breast cancer receiving gemcitabine and carboplatin chemotherapy. The final myelopreservation efficacy results are reported from database lock 1 ([DBL1], data cut-off [DCO] date of 30 July 2018). Final anti-tumor efficacy (ORR, PFS), and final summary exposure and safety data are reported from database lock 2 ([DBL2], DCO 28 June 2019) which occurred to support filing of the trilaciclib New Drug Application (NDA). Final overall survival (OS) data are reported from the final database lock which occurred on 17 July 2020 (with a last patient last visit date of 28 February 2020).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Triple-Negative Breast Neoplasms, Breast Neoplasm, Breast Cancer, Triple-Negative Breast Cancer

Keywords

Breast Cancer, CDK 4/6 Inhibitor, Triple Negative Breast Cancer, Metastatic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

102 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: Gemcitabine/Carboplatin (Days 1 and 8)

Arm Type

Experimental

Arm Description

Arm Title

Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8)

Arm Type

Experimental

Arm Description

Arm Title

Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Trilaciclib

Other Intervention Name(s)

G1T28, CDK 4/6 Inhibitor

Intervention Description

G1T28

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Intervention Description

Gemcitabine

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

Carboplatin

Primary Outcome Measure Information:

Title

Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1

Description

Time Frame

From randomization to the end of Cycle 1 (Each cycle= 21 days)

Title

Number of Participants With Severe (Grade 4) Neutropenia (SN)

Description

Time Frame

During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Secondary Outcome Measure Information:

Title

Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Description

Time Frame

From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days

Title

Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator

Description

Time Frame

From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days

Title

Overall Survival (OS)

Description

Time Frame

From date of randomization to date of death due to any cause, assessed up to a maximum of 1120 days

Title

Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator

Description

Time Frame

From date of randomization until the occurrence of disease progression, death due to any cause or a censoring event, assessed up to a maximum of 875 days

Title

Relative Dose Intensity of Gemcitabine and Carboplatin

Description

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 871 days

Title

Duration of Exposure

Description

Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21.

Time Frame

Title

Number of Cycles Participants Received Treatment in Each Treatment Arm

Description

Participants were considered to have started a cycle if they have received at least 1 dose of any study drug.

Time Frame

Title

Cumulative Dose of Gemcitabine

Description

Cumulative dose: Sum of the total doses by cycle administered to a participant in the duration of exposure, i.e. total number of cycles received (milligram per meter square [mg/m^2]).

Time Frame

Title

Cumulative Dose of Carboplatin

Description

Cumulative dose: Sum of the total doses by cycle (AUC) administered to a participant in the duration of exposure, i.e. total number of cycles received (in total prescribed AUC).

Time Frame

Title

Maximum Observed Plasma Concentration (Cmax) of Trilaciclib

Description

The observed peak plasma concentration was determined from the plasma concentration-versus time data.

Time Frame

Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Title

Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib

Description

Time Frame

Title

Terminal Elimination Half-Life (t1/2) of Trilaciclib

Description

Time Frame

Title

Maximum Observed Plasma Concentration (Cmax) of Gemcitabine

Description

The observed peak plasma concentration was determined from the plasma concentration-versus time data.

Time Frame

Title

Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine

Description

AUC0-t was calculated with the linear/log-trapezoidal method.

Time Frame

Title

Terminal Elimination Half-Life (t1/2) of Free Carboplatin

Description

Time Frame

Title

Clearance (CL) of of Free Carboplatin

Description

Time Frame

Title

Volume of Distribution at Steady State (Vss) of Free Carboplatin

Description

Vss was the volume of distribution at steady state of free carboplatin was reported.

Time Frame

Title

Number of Participants With Grade 3 and 4 Hematologic Toxicities

Description

Time Frame

Title

Number of Participants With Grade 3 or 4 Thrombocytopenia

Description

Time Frame

Title

Major Adverse Hematologic Event (MAHE) Rate

Description

Time Frame

Title

Number of Participants With Febrile Neutropenia (FN)

Description

Time Frame

Title

Number of Participants With Infection SAEs

Description

Time Frame

Title

Number of Participants With Red Blood Cell (RBC) Transfusions On/After Week 5 (Day 35)

Description

Time Frame

From Day 35 through the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 508 days

Title

Number of Participants With Platelet Transfusions

Description

Time Frame

Title

Number of Participants With Granulocyte Colony-stimulating Factor (G-CSF) Administration

Description

Time Frame

Title

Number of Participants With Erythropoiesis Stimulating Agent (ESA) Administration

Description

Time Frame

Title

Number of Participants With Intravenous Antibiotics Use

Description

Time Frame

Title

All-cause Dose Reductions, Event Rate (Per Cycle)

Description

Time Frame

Title

Dose Modifications: Number of Participants With Cycle Delays

Description

Time Frame

Title

Dose Modifications - Number of Participants With Skipped Doses

Description

Time Frame

Title

Dose Modifications: Number of Participants With Any Dose Interruptions

Description

Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.

Time Frame

Title

Dose Modifications - Number of Participants With Dose Reductions

Description

Time Frame

Other Pre-specified Outcome Measures:

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

Description

An Adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. Any AE that started on or after the first dose of study drugs was included as a TEAE. A Serious AE was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) and regardless of causality that met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. TEAEs included serious and non-serious TEAEs.

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Confirmed diagnosis of hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-negative (locally recurrent or metastatic TNBC) breast cancer Available TNBC diagnostic tumor tissue (archived tissue allowed) Evaluable disease Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 Adequate organ function Predicted life expectancy of 3 or more months Exclusion Criteria: More than 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC. If > 12 months have elapsed between the date of last adjuvant/neoadjuvant chemotherapy administration and first documented local or distant disease recurrence the therapy will not be considered a line of therapy in the locally recurrent or metastatic TNBC setting. CNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids. Investigational drug within 30 days of first trilaciclib (G1T28) dose Concurrent radiotherapy, radiotherapy within 14 days of first trilaciclib (G1T28) dose Cytotoxic chemotherapy within 3 weeks of first trilaciclib (G1T28) dose Prior hematopoietic stem cell or bone marrow transplantation

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Contact

Organizational Affiliation

G1 Therapeutics, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Arizona Oncology Associates, PC - HOPE

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85704

Country

United States

Facility Name

Disney Family Cancer Center

City

Burbank

State/Province

California

ZIP/Postal Code

91505

Country

United States

Facility Name

Sharp Clinical Oncology

City

San Diego

State/Province

California

ZIP/Postal Code

92123

Country

United States

Facility Name

Innovative Clinical Research Institute

City

Whittier

State/Province

California

ZIP/Postal Code

90603

Country

United States

Facility Name

Memorial UC Health

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80909

Country

United States

Facility Name

Rocky Mountain Cancer Centers

City

Lakewood

State/Province

Colorado

ZIP/Postal Code

80228

Country

United States

Facility Name

Florida Cancer Specialists

City

Fort Myers

State/Province

Florida

ZIP/Postal Code

33916

Country

United States

Facility Name

Florida Cancer Research Institute, LLC.

City

Plantation

State/Province

Florida

ZIP/Postal Code

33324

Country

United States

Facility Name

Florida Cancer Specialists - North (FCS North)

City

Saint Petersburg

State/Province

Florida

ZIP/Postal Code

33705

Country

United States

Facility Name

Moffitt Cancer Center

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

Florida Cancer Specialists - East (FCS East)

City

West Palm Beach

State/Province

Florida

ZIP/Postal Code

33401

Country

United States

Facility Name

Saint Alphonsus Regional Medical Center

City

Boise

State/Province

Idaho

ZIP/Postal Code

83706

Country

United States

Facility Name

Illinois Cancer Specialists

City

Arlington Heights

State/Province

Illinois

ZIP/Postal Code

60005

Country

United States

Facility Name

Community Health Network

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46250

Country

United States

Facility Name

University of Maryland Greenebaum Comprehensive Cancer Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201-1544

Country

United States

Facility Name

The University of Maryland St. Joseph Medical Center

City

Towson

State/Province

Maryland

ZIP/Postal Code

21204

Country

United States

Facility Name

Saint Luke's Cancer Institute

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64113

Country

United States

Facility Name

Comprehensive Cancer Centers of Nevada

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89128

Country

United States

Facility Name

Levine Cancer Center

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

Forsyth Memorial Hospital, Novant Health Oncology Specialists

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27103

Country

United States

Facility Name

Tennessee Oncology

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37404

Country

United States

Facility Name

Tennessee Oncology

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Texas Oncology-Dallas Presbyterian Hospital

City

Austin

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Texas Oncology, P.A.

City

Austin

State/Province

Texas

ZIP/Postal Code

78745

Country

United States

Facility Name

Texas Oncology, P.A.

City

Bedford

State/Province

Texas

ZIP/Postal Code

76022

Country

United States

Facility Name

Texas Oncology - Baylor Charles A. Sammons Cancer Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Texas Oncology-El Paso Cancer Treatment Center Grandview

City

El Paso

State/Province

Texas

ZIP/Postal Code

79902

Country

United States

Facility Name

The Center for Cancer and Blood Disorders

City

Fort Worth

State/Province

Texas

ZIP/Postal Code

76104

Country

United States

Facility Name

Texas Oncology-San Antonio Northeast

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78217

Country

United States

Facility Name

Tyler Hematology-Oncology, PA

City

Tyler

State/Province

Texas

ZIP/Postal Code

75701

Country

United States

Facility Name

Texas Oncology, P.A.

City

Tyler

State/Province

Texas

ZIP/Postal Code

75702

Country

United States

Facility Name

University of Virginia

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22908

Country

United States

Facility Name

Virginia Cancer Specialists, PC

City

Fairfax

State/Province

Virginia

ZIP/Postal Code

22031

Country

United States

Facility Name

Virginia Oncology Associates

City

Virginia Beach

State/Province

Virginia

ZIP/Postal Code

23456

Country

United States

Facility Name

Northwest Medical Specialties, PLLC

City

Tacoma

State/Province

Washington

ZIP/Postal Code

98405

Country

United States

Facility Name

Antwerp University Hospital (UZA)

City

Edegem

ZIP/Postal Code

10 2650

Country

Belgium

Facility Name

University Multiprofile Hospital for Active Treatment

City

Sofia

ZIP/Postal Code

1000

Country

Bulgaria

Facility Name

MHAT for Womens Health - Nadezhda OOD

City

Sofia

ZIP/Postal Code

1330

Country

Bulgaria

Facility Name

Special Hospital For Active Treatment In Oncology

City

Sofia

ZIP/Postal Code

1756

Country

Bulgaria

Facility Name

Multiprofile Hospital for Active Treatment

City

Varna

ZIP/Postal Code

9000

Country

Bulgaria

Facility Name

University Hospital Centre Osijek

City

Osijek

ZIP/Postal Code

31000

Country

Croatia

Facility Name

General Hospital Varaždin

City

Varazdin

ZIP/Postal Code

42000

Country

Croatia

Facility Name

University Hospital Centre "Sestre milosrdnice"

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

University Hospital Centre Zagreb

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

Clinical Hospital Dr. Trifun Panovski

City

Bitola

ZIP/Postal Code

7000

Country

North Macedonia

Facility Name

University Clinic of Radiotherapy and Oncology

City

Skopje

ZIP/Postal Code

1000

Country

North Macedonia

Facility Name

Special Hospital for Internal Diseases , Oncomed

City

Belgrade

ZIP/Postal Code

11000

Country

Serbia

Facility Name

Clinical Hospital Centre Bezanijska Kosa, Oncology Clinic

City

Belgrade

ZIP/Postal Code

11070

Country

Serbia

Facility Name

Center for Oncology and Radiotherapy, Clinical Centre

City

Kragujevac

ZIP/Postal Code

34000

Country

Serbia

Facility Name

Clinical Centre Nis, Clinic of Oncology

City

Nis

ZIP/Postal Code

18000

Country

Serbia

Facility Name

Oncology Institute of Vojvodina, Clinic for Internal Oncology

City

Sremska Kamenica

ZIP/Postal Code

21204

Country

Serbia

Facility Name

Mammacentrum, Sv.Agáty

City

Banská Bystrica

ZIP/Postal Code

974 01

Country

Slovakia

Facility Name

Cancer Institute VOU, Rastislavova

City

Košice

ZIP/Postal Code

040 01

Country

Slovakia

Facility Name

University Medical Centre Maribor

City

Maribor

ZIP/Postal Code

2000

Country

Slovenia

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

31575503

Citation

Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnovic Z, Vasev N, Ma L, Richards DA, Wilks ST, Milenkovic D, Yang Z, Antal JM, Morris SR, O'Shaughnessy J. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2019 Nov;20(11):1587-1601. doi: 10.1016/S1470-2045(19)30616-3. Epub 2019 Sep 28.

Results Reference

background

PubMed Identifier

34887261

Citation

Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnovic Z, Vasev N, Ma L, Richards DA, Wilks ST, Milenkovic D, Xiao J, Sorrentino J, Horton J, O'Shaughnessy J. Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study. Clin Cancer Res. 2022 Feb 15;28(4):629-636. doi: 10.1158/1078-0432.CCR-21-2272.

Results Reference

background

Learn more about this trial

Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)

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