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

NCT02978716 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: G1T28-042016-004466-26
• Study Type: interventional
• Target: 102
• Locations: 7 countries
• Sites: 53

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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".

  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 Outcomes (32)

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

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

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

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

• Overall Survival (OS)

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

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

  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

• Relative Dose Intensity of Gemcitabine and Carboplatin

  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

Other Outcomes (1)

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

  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 1116 days

Study Arms (3)

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

EXPERIMENTAL

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).

Drug: Gemcitabine; Drug: Carboplatin

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

EXPERIMENTAL

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.

Drug: Trilaciclib; Drug: Gemcitabine; Drug: Carboplatin

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

EXPERIMENTAL

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.

Drug: Trilaciclib; Drug: Gemcitabine; Drug: Carboplatin

Interventions

Trilaciclib DRUG

G1T28

Also known as: G1T28, CDK 4/6 Inhibitor

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

Gemcitabine DRUG

Gemcitabine

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)

Carboplatin DRUG

Carboplatin

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (54)

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85704, United States

Location

Disney Family Cancer Center

Burbank, California, 91505, United States

Location

Sharp Clinical Oncology

San Diego, California, 92123, United States

Location

Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Memorial UC Health

Colorado Springs, Colorado, 80909, United States

Location

Rocky Mountain Cancer Centers

Lakewood, Colorado, 80228, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Research Institute, LLC.

Plantation, Florida, 33324, United States

Location

Florida Cancer Specialists - North (FCS North)

St. Petersburg, Florida, 33705, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Florida Cancer Specialists - East (FCS East)

West Palm Beach, Florida, 33401, United States

Location

Saint Alphonsus Regional Medical Center

Boise, Idaho, 83706, United States

Location

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

Location

Community Health Network

Indianapolis, Indiana, 46250, United States

Location

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201-1544, United States

Location

The University of Maryland St. Joseph Medical Center

Towson, Maryland, 21204, United States

Location

Saint Luke's Cancer Institute

Kansas City, Missouri, 64113, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89128, United States

Location

Levine Cancer Center

Charlotte, North Carolina, 28204, United States

Location

Forsyth Memorial Hospital, Novant Health Oncology Specialists

Winston-Salem, North Carolina, 27103, United States

Location

Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology-Dallas Presbyterian Hospital

Austin, Texas, 75231, United States

Location

Texas Oncology, P.A.

Austin, Texas, 78745, United States

Location

Texas Oncology, P.A.

Bedford, Texas, 76022, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology-El Paso Cancer Treatment Center Grandview

El Paso, Texas, 79902, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Texas Oncology-San Antonio Northeast

San Antonio, Texas, 78217, United States

Location

Tyler Hematology-Oncology, PA

Tyler, Texas, 75701, United States

Location

Texas Oncology, P.A.

Tyler, Texas, 75702, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates

Virginia Beach, Virginia, 23456, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

Antwerp University Hospital (UZA)

Edegem, 10 2650, Belgium

Location

University Multiprofile Hospital for Active Treatment

Sofia, 1000, Bulgaria

Location

MHAT for Womens Health - Nadezhda OOD

Sofia, 1330, Bulgaria

Location

Special Hospital For Active Treatment In Oncology

Sofia, 1756, Bulgaria

Location

Multiprofile Hospital for Active Treatment

Varna, 9000, Bulgaria

Location

University Hospital Centre Osijek

Osijek, 31000, Croatia

Location

General Hospital Varaždin

Varaždin, 42000, Croatia

Location

University Hospital Centre "Sestre milosrdnice"

Zagreb, 10000, Croatia

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Clinical Hospital Dr. Trifun Panovski

Bitola, 7000, North Macedonia

Location

University Clinic of Radiotherapy and Oncology

Skopje, 1000, North Macedonia

Location

Special Hospital for Internal Diseases , Oncomed

Belgrade, 11000, Serbia

Location

Clinical Hospital Centre Bezanijska Kosa, Oncology Clinic

Belgrade, 11070, Serbia

Location

Oncology Institute of Vojvodina, Clinic for Internal Oncology

Kamenitz, 21204, Serbia

Location

Center for Oncology and Radiotherapy, Clinical Centre

Kragujevac, 34000, Serbia

Location

Clinical Centre Nis, Clinic of Oncology

Niš, 18000, Serbia

Location

Mammacentrum, Sv.Agáty

Banská Bystrica, 974 01, Slovakia

Location

Cancer Institute VOU, Rastislavova

Košice, 040 01, Slovakia

Location

University Medical Centre Maribor

Maribor, 2000, Slovenia

Location

Related Publications (2)

• 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.

  PMID: 31575503 BACKGROUND

• 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.

  PMID: 34887261 BACKGROUND

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms; Neoplasm Metastasis

Interventions

trilaciclib; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Limitations and Caveats

Limitations of this study are the small sample size and open-label design. Antitumor outcomes were not the primary endpoints.

Results Point of Contact

• Title: Clinical Trial Info
• Organization: G1 Therapeutics, Inc

clinicalinfo@g1therapeutics.com

+1 9192139835

Study Officials

• Clinical Contact

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: December 1, 2016
• Study Start: February 2, 2017
• Primary Completion: June 28, 2019
• Study Completion: February 28, 2020
• Last Updated: March 23, 2022
• Results First Posted: March 23, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2); US (35); SE (5); SL (2); CR (4); BU (4); BE (1)