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

NCT ID: NCT02978716

Last Updated: 2022-03-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-02
• Study Completion Date: 2020-02-28

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).

Conditions

Triple-Negative Breast Neoplasms; Breast Neoplasm; Breast Cancer; Triple-Negative Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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).

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Gemcitabine

Carboplatin

Intervention Type: DRUG

Carboplatin

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

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.

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

G1T28

Gemcitabine

Intervention Type: DRUG

Gemcitabine

Carboplatin

Intervention Type: DRUG

Carboplatin

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

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.

Group Type: EXPERIMENTAL

Trilaciclib

Intervention Type: DRUG

G1T28

Gemcitabine

Intervention Type: DRUG

Gemcitabine

Carboplatin

Intervention Type: DRUG

Carboplatin

Interventions

Trilaciclib

G1T28

Intervention Type: DRUG

Gemcitabine

Gemcitabine

Intervention Type: DRUG

Carboplatin

Carboplatin

Intervention Type: DRUG

Other Intervention Names

G1T28; CDK 4/6 Inhibitor

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

• 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

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, United States

Disney Family Cancer Center

Burbank, California, United States

Sharp Clinical Oncology

San Diego, California, United States

Innovative Clinical Research Institute

Whittier, California, United States

Memorial UC Health

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers

Lakewood, Colorado, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Florida Cancer Research Institute, LLC.

Plantation, Florida, United States

Florida Cancer Specialists - North (FCS North)

St. Petersburg, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Florida Cancer Specialists - East (FCS East)

West Palm Beach, Florida, United States

Saint Alphonsus Regional Medical Center

Boise, Idaho, United States

Illinois Cancer Specialists

Arlington Heights, Illinois, United States

Community Health Network

Indianapolis, Indiana, United States

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

The University of Maryland St. Joseph Medical Center

Towson, Maryland, United States

Saint Luke's Cancer Institute

Kansas City, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Levine Cancer Center

Charlotte, North Carolina, United States

Forsyth Memorial Hospital, Novant Health Oncology Specialists

Winston-Salem, North Carolina, United States

Tennessee Oncology

Chattanooga, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

Texas Oncology-Dallas Presbyterian Hospital

Austin, Texas, United States

Texas Oncology, P.A.

Austin, Texas, United States

Texas Oncology, P.A.

Bedford, Texas, United States

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Texas Oncology-El Paso Cancer Treatment Center Grandview

El Paso, Texas, United States

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Texas Oncology-San Antonio Northeast

San Antonio, Texas, United States

Tyler Hematology-Oncology, PA

Tyler, Texas, United States

Texas Oncology, P.A.

Tyler, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Virginia Oncology Associates

Virginia Beach, Virginia, United States

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States

Antwerp University Hospital (UZA)

Edegem, , Belgium

University Multiprofile Hospital for Active Treatment

Sofia, , Bulgaria

MHAT for Womens Health - Nadezhda OOD

Sofia, , Bulgaria

Special Hospital For Active Treatment In Oncology

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment

Varna, , Bulgaria

University Hospital Centre Osijek

Osijek, , Croatia

General Hospital Varaždin

Varaždin, , Croatia

University Hospital Centre "Sestre milosrdnice"

Zagreb, , Croatia

University Hospital Centre Zagreb

Zagreb, , Croatia

Clinical Hospital Dr. Trifun Panovski

Bitola, , North Macedonia

University Clinic of Radiotherapy and Oncology

Skopje, , North Macedonia

Special Hospital for Internal Diseases , Oncomed

Belgrade, , Serbia

Clinical Hospital Centre Bezanijska Kosa, Oncology Clinic

Belgrade, , Serbia

Oncology Institute of Vojvodina, Clinic for Internal Oncology

Kamenitz, , Serbia

Center for Oncology and Radiotherapy, Clinical Centre

Kragujevac, , Serbia

Clinical Centre Nis, Clinic of Oncology

Niš, , Serbia

Mammacentrum, Sv.Agáty

Banská Bystrica, , Slovakia

Cancer Institute VOU, Rastislavova

Košice, , Slovakia

University Medical Centre Maribor

Maribor, , Slovenia

Countries

United States; Belgium; Bulgaria; Croatia; North Macedonia; Serbia; Slovakia; Slovenia

References

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.

Reference Type: BACKGROUND

PMID: 31575503 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34887261 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004466-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

G1T28-04

Identifier Type: -

Identifier Source: org_study_id