Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC)

NCT04799249 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: G1T28-2082020-004930-39
• Study Type: interventional
• Target: 194
• Locations: 11 countries
• Sites: 71

Brief Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of trilaciclib versus placebo administered prior to gemcitabine and carboplatin in patients receiving first- or second-line treatment for locally advanced unresectable/metastatic TNBC.

Conditions

TNBC - Triple-Negative Breast Cancer; Breast Cancer

Keywords

breast cancer; gemcitabine; carboplatin; solid tumors; breast; chemotherapy; TNBC; trilaciclib; cyclin-dependent kinase 4/6 inhibitor; CDK 4/6 Inhibitor; triple-negative breast cancer; metastatic; chemotherapy-induced fatigue; HER2-negative; immunotherapy; immune checkpoint inhibitor therapy; chemotherapy-induced myelosuppression; myeloprotection; myeloprotective; PD-1/PD-L1 inhibitor therapy; advanced; stage 4; preserve; PRESERVE 2

Outcome Measures

Primary Outcomes (2)

• Effect on Overall Survival (OS)

  (Cohort 1):To evaluate the effect of trilaciclib on overall survival (OS) compared with placebo in patients receiving first-line gemcitabine and carboplatin.

  Cohort 1:From date of randomization up to 39 months

• Effect on Overall Survival (OS)

  (Cohort 2): To evaluate the effect of trilaciclib on OS compared with placebo in patients receiving gemcitabine and carboplatin as second-line therapy after treatment with a PD-1/PD-L1 inhibitor in the locally advanced unresectable/metastatic setting

  Cohort 2: From date of randomization up to 28 months

Secondary Outcomes (3)

• Quality of life/Effects On Chemotherapy-Induced Fatigue

  Cycle 1 Day 1 (each cycle is 21 days) up to 14 months

• Myeloprotective Effects

  Cycle 1 Day 1 (each cycle is 21 days) up to 14 months

• Progression Free Survival

  From date of randomization up to 14 months)

Study Arms (2)

Trilaciclib + gemcitabine + carboplatin

EXPERIMENTAL

Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)

Drug: Trilaciclib; Drug: Gemcitabine; Drug: Carboplatin

Placebo + gemcitabine + carboplatin

PLACEBO COMPARATOR

The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.

Drug: Placebo; Drug: Gemcitabine; Drug: Carboplatin

Interventions

Trilaciclib DRUG

Trilaciclib administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.

Also known as: G1T28, COSELA

Trilaciclib + gemcitabine + carboplatin

Placebo DRUG

Placebo administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.

Also known as: 0.9% normal saline, 5 % Dextrose in water (D5W)

Placebo + gemcitabine + carboplatin

Gemcitabine DRUG

Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle.

Placebo + gemcitabine + carboplatin; Trilaciclib + gemcitabine + carboplatin

Carboplatin DRUG

Carboplatin administered IV on Day 1 and Day 8 of each 21-day cycle.

Placebo + gemcitabine + carboplatin; Trilaciclib + gemcitabine + carboplatin

Eligibility Criteria

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

You may qualify if:

• Age \>/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.
• Documentation of triple negative breast cancer (estrogen and progesterone receptor \<1% and HER2-negative)
• Prior systemic therapies (Cohort 1 only):
• No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
• Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
• Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.
• Prior systemic therapies (Cohort 2 only):
• Documentation of PD-L1 positive status
• Treated with a PD-1/PD-L1 inhibitor for a minimum duration of 4 months in the locally advanced unresectable/metastatic setting and as the most recent therapy.
• Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Patients should be recovered from the effects of radiation.
• Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function as demonstrated by normal laboratory values

You may not qualify if:

• Prior treatment with gemcitabine in any setting.
• Prior treatment with carboplatin in the locally advanced unresectable/metastatic setting.
• Prior carboplatin in the (neo)adjuvant/curative setting is permitted as long as it was completed ≥ 6 months prior to the first metastatic recurrence.
• Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
• Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.
• QTcF interval \>480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF \>500 msec.
• Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol
• Pregnant or lactating women
• Prior hematopoietic stem cell or bone marrow transplantation

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (71)

Banner M.D. Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Washington Cancer Institute at MedStar Washington Hospital Center - Oncology Research

Washington D.C., District of Columbia, 20010, United States

Location

Florida Cancer Specialists - North (SCRI)

St. Petersburg, Florida, 33705, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Maryland Oncology Hematology, P.A.

Clinton, Maryland, 20735, United States

Location

Saint Luke's Cancer Specialists

Kansas City, Missouri, 64111, United States

Location

Comprehensive Cancer Genetics of Nevada

Las Vegas, Nevada, 89128, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

UPC Pinnacle Health Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Baptist Cancer Cancer - Oncology

Memphis, Tennessee, 38120, United States

Location

Tennessee Oncology (SCRI)

Nashville, Tennessee, 37203, United States

Location

Texas Oncology- Austin Central

Austin, Texas, 78731, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology P.A.

Tyler, Texas, 75702, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Peter MacCallum Cancer Centre - Oncology

East Melbourne, Victoria, 08006, Australia

Location

Cabrini Health

Malvern, Victoria, 3144, Australia

Location

Mater Hospital Sydney

North Sydney, 2060, Australia

Location

Complex Oncology Center - Burgas

Burgas, 8000, Bulgaria

Location

Medical Ctr Nadezhda Clinical

Sofia, 1330, Bulgaria

Location

Cancer Hospital Chinese Academy of Medical Sciences

Chaoyang, Beijing Municipality, 100021, China

Location

The First Affiliated Hospital of Chongqing Medical University

Yuzhong, Chongqing Municipality, 401122, China

Location

Sun Yat-sen University Cancer Center

Yuexiucun, Guangzhou, 510060, China

Location

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050011, China

Location

Anhui Provincial Hospital

Harbin, Heilongjiang, 150081, China

Location

First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130021, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 450052, China

Location

Centre Jean Bernard

Le Mans, Europe, 72000, France

Location

Centre Francois Baclesse

Caen, 14000, France

Location

ICM-Val d'Aurelle

Montpellier, 34298, France

Location

Centre Hospitalier de Poitiers

Poitiers, 86000, France

Location

Pharmacie Essais Cliniques

Toulouse, 31100, France

Location

Centre Leon Berard

Villejuif, 94800, France

Location

High Technology Hospital MedCenter LTD

Batumi, Adjara, 6010, Georgia

Location

Acad.Fridon Todua Medical Center - Research Institute of Clinical Medicine

Tbilisi, 0112, Georgia

Location

ARENSIA Exploratory Medicine Harmony Health

Tbilisi, 0112, Georgia

Location

LTD Israeli-Georgian Medical Research Clinic Helsicore

Tbilisi, 0112, Georgia

Location

LTD Multiprofile Clinic Consilium Medulla

Tbilisi, 0186, Georgia

Location

TIM - Tbilisi Institute of Medicine LTD

Tbilisi, 0186, Georgia

Location

Institute Of Clinical Oncology LTD

Tbilisi, 159, Georgia

Location

IMSP Institutul Oncologic, ARENSIA Exploratory Medicine

Chisinau, MD-2025, Moldova

Location

Med-Polonia Sp. Z o.o.

Poznan, Greater Poland Voivodeship, 60-569, Poland

Location

Pratia MCM Krakow

Krakow, Lesser Poland Voivodeship, 30-510, Poland

Location

Instytut MSF Sp. z. o.o.

Lodz, 90-302, Poland

Location

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi, Oddzial Chorob Rozrostowych

Lodz, 93-513, Poland

Location

Centrum Medyczne Pratia Poznan

Skorzewo, 60-185, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej - Curie - Panstwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Oncology Dispensary"

Moscow, Balashikha, 143900, Russia

Location

SAHI Republcx Clinical Oncology Dispensary of the Ministry of Healthcare of Tatarstan Republix

Kazan', 420029, Russia

Location

FSBI Russian Scientific Center of Roentgenoradiology of the MoH of Russia

Moscow, 117997, Russia

Location

State Budgetary Healthcare Institution of Moscow Region "Moscow Reginoal Oncology Dispensary"

Moscow, 143900, Russia

Location

Budgetary Healthcare Institution of Omsk Region "Clinical Oncological Dispensary"

Omsk, 644013, Russia

Location

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

Location

Hospital Puerta de Hierro Majadahonda

Madrid, Majadahonda, 28222, Spain

Location

Hospital Universitario de Badajos

Badajoz, 06006, Spain

Location

Hospital Universitario 12 de Octubre

Barcelona, 08035, Spain

Location

Vall d'Hebrón University Hospital

Barcelona, 08035, Spain

Location

Hospital Clìnic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Yuri Prokopovich Spizhenko

Kapitanivka, Kyivska Oblast, 08112, Ukraine

Location

Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady Sumskyi oblasnyi onkolohichnyi dyspanser

Sumy, Sumska Oblast, 40022, Ukraine

Location

Komunalne nekomertsiine pidpryiemstvo Ternopilskyi oblasnyi klinichnyi onkolohichnyi dyspanser Ternopilskoi oblasnoi rady

Ternopil, Ternopil Oblast, 46023, Ukraine

Location

Volynskyi oblasnyi medychnyi tsentr onkolohii

Lutsk, Volyn Oblast, 63000, Ukraine

Location

Komunalne nekomertsiine pidpryiemstvo Miska klinichna likarnia No 4 Dniprovskoi miskoi rady

Dnipro, 49102, Ukraine

Location

Related Publications (1)

• Goel S, Tan AR, Rugo HS, Aftimos P, Andric Z, Beelen A, Zhang J, Yi JS, Malik R, O'Shaughnessy J. Trilaciclib prior to gemcitabine plus carboplatin for metastatic triple-negative breast cancer: phase III PRESERVE 2. Future Oncol. 2022 Oct;18(33):3701-3711. doi: 10.2217/fon-2022-0773. Epub 2022 Sep 22.

  PMID: 36135712 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms; Neoplasm Metastasis

Interventions

trilaciclib; Saline Solution; Glucose; Water; 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)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Clinical Contact

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-Blind Trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: March 16, 2021
• Study Start: May 14, 2021
• Primary Completion: May 24, 2024
• Study Completion: May 24, 2024
• Last Updated: August 1, 2024

Record last verified: 2024-07

Locations

UA (5); GE (7); AU (5); ES (7); US (16); FR (6); CN (11); MO (1); BU (2); PL (6); RU (5)