Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC) (PRESERVE 2)

July 31, 2024 updated by: G1 Therapeutics, Inc.

A Phase 3, Randomized, Double-Blind Study of Trilaciclib or Placebo in Patients Receiving First- or Second-Line Gemcitabine and Carboplatin Chemotherapy for Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (PRESERVE 2)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will have two separate cohorts (Cohort 1 and Cohort 2). Both cohorts will follow the same general study conduct/design with similar primary and key secondary endpoints and identical treatment arms.

  • Cohort 1 will evaluate patients receiving first-line therapy, regardless of programmed death-ligand 1 (PD-L1) status, who are programmed cell death protein 1 (PD-1)/PD-L1 inhibitor therapy naïve.
  • Cohort 2 will evaluate PD-L1 positive patients receiving second-line therapy following prior PD-1/PD-L1 inhibitor therapy in the locally advanced unresectable/metastatic setting.

Study Type

Interventional

Enrollment (Actual)

194

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • North Sydney, Australia, 2060
        • Mater Hospital Sydney
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris O'Brien Lifehouse
    • Queensland
      • Birtinya, Queensland, Australia, 4575
        • Sunshine Coast University Hospital
    • Victoria
      • East Melbourne, Victoria, Australia, 08006
        • Peter MacCallum Cancer Centre - Oncology
      • Malvern, Victoria, Australia, 3144
        • Cabrini Health
  • Bulgaria
      • Burgas, Bulgaria, 8000
        • Complex Oncology Center - Burgas
      • Sofia, Bulgaria, 1330
        • Medical Ctr Nadezhda Clinical
  • China
      • Shanghai, China, 450052
        • Fudan University Shanghai Cancer Center
    • Beijing
      • Chaoyang, Beijing, China, 100021
        • Cancer Hospital Chinese Academy of Medical Sciences
    • Chongqing
      • Yuzhong, Chongqing, China, 401122
        • The First Affiliated Hospital of Chongqing Medical University
    • Guangzhou
      • Yuexiu, Guangzhou, China, 510060
        • Sun yat-sen University Cancer Center
    • Hebei
      • Shijiazhuang, Hebei, China, 050011
        • The Fourth Hospital of Hebei Medical University
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Anhui Provincial Hospital
    • Henan
      • Zhengzhou, Henan, China, 450052
        • First Affiliated Hospital of Zhengzhou University
    • Jilin
      • Changchun, Jilin, China, 130021
        • The First Hospital of Jilin University
      • Changchun, Jilin, China, 130021
        • Jilin Cancer Hospital
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Tianjin Cancer Hospital
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • Zhejiang Cancer Hospital
  • France
      • Caen, France, 14000
        • Centre Francois Baclesse
      • Montpellier, France, 34298
        • ICM-Val d'Aurelle
      • Poitiers, France, 86000
        • Centre Hospitalier de Poitiers
      • Toulouse, France, 31100
        • Pharmacie Essais Cliniques
      • Villejuif, France, 94800
        • Centre Leon Berard
    • Europe
      • Le Mans, Europe, France, 72000
        • Centre Jean Bernard
  • Georgia
      • Tbilisi, Georgia, 0186
        • ltd Multiprofile Clinic Consilium Medulla
      • Tbilisi, Georgia, 0112
        • Ltd Israeli-Georgian Medical Research Clinic Helsicore
      • Tbilisi, Georgia, 0112
        • Acad.Fridon Todua Medical Center - Research Institute of Clinical Medicine
      • Tbilisi, Georgia, 0112
        • ARENSIA Exploratory Medicine Harmony Health
      • Tbilisi, Georgia, 0186
        • TIM - Tbilisi Institute of Medicine LTD
      • Tbilisi, Georgia, 159
        • Institute of Clinical Oncology Ltd
    • Ajaria
      • Batumi, Ajaria, Georgia, 6010
        • High Technology Hospital MedCenter Ltd
  • Moldova, Republic of
      • Chisinau, Moldova, Republic of, MD-2025
        • IMSP Institutul Oncologic, ARENSIA Exploratory Medicine
  • Poland
      • Lodz, Poland, 93-513
        • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi, Oddzial Chorob Rozrostowych
      • Skorzewo, Poland, 60-185
        • Centrum Medyczne Pratia Poznań
      • Warszawa, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej - Curie - Panstwowy Instytut Badawczy
      • Łódź, Poland, 90-302
        • Instytut MSF Sp. z. o.o.
    • Malopolskie
      • Krakow, Malopolskie, Poland, 30-510
        • PRATIA MCM Kraków
    • Wielkopolskie
      • Poznan, Wielkopolskie, Poland, 60-569
        • Med-Polonia Sp. z o.o.
  • Russian Federation
      • Kazan, Russian Federation, 420029
        • SAHI Republcx Clinical Oncology Dispensary of the Ministry of Healthcare of Tatarstan Republix
      • Moscow, Russian Federation, 117997
        • FSBI Russian Scientific Center of Roentgenoradiology of the MoH of Russia
      • Moscow, Russian Federation, 143900
        • State Budgetary Healthcare Institution of Moscow Region "Moscow Reginoal Oncology Dispensary"
      • Omsk, Russian Federation, 644013
        • Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary"
    • Balashikha
      • Moscow, Balashikha, Russian Federation, 143900
        • Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Oncology Dispensary"
  • Spain
      • Badajoz, Spain, 06006
        • Hospital Universitario de Badajos
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • Barcelona, Spain, 08035
        • Vall d'Hebron University Hospital
      • Barcelona, Spain, 08035
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche
    • Majadahonda
      • Madrid, Majadahonda, Spain, 28222
        • Hospital Puerta de Hierro Majadahonda
  • Ukraine
      • Dnipro, Ukraine, 49102
        • Komunalne nekomertsiine pidpryiemstvo Miska klinichna likarnia No 4 Dniprovskoi miskoi rady
    • Kyivska Oblast
      • Kapitanivka, Kyivska Oblast, Ukraine, 08112
        • Yuri Prokopovich Spizhenko
    • Sums'ka Oblast
      • Sumy, Sums'ka Oblast, Ukraine, 40022
        • Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady Sumskyi oblasnyi onkolohichnyi dyspanser
    • Ternopil's'ka Oblast
      • Ternopil, Ternopil's'ka Oblast, Ukraine, 46023
        • Komunalne nekomertsiine pidpryiemstvo Ternopilskyi oblasnyi klinichnyi onkolohichnyi dyspanser Ternopilskoi oblasnoi rady
    • Volyns'ka Oblast
      • Lutsk, Volyns'ka Oblast, Ukraine, 63000
        • Volynskyi oblasnyi medychnyi tsentr onkolohii
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner M.D. Anderson Cancer Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Washington Cancer Institute at MedStar Washington Hospital Center - Oncology Research
    • Florida
      • Saint Petersburg, Florida, United States, 33705
        • Florida Cancer Specialists - North (SCRI)
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Maryland
      • Clinton, Maryland, United States, 20735
        • Maryland Oncology Hematology, P.A.
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Cancer Specialists
    • Nevada
      • Las Vegas, Nevada, United States, 89128
        • Comprehensive Cancer Genetics of Nevada
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Cancer Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPC Pinnacle Health Cancer Institute
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Tennessee Oncology Chattanooga
      • Memphis, Tennessee, United States, 38120
        • Baptist Cancer Cancer - Oncology
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology (SCRI)
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology- Austin Central
      • Dallas, Texas, United States, 75246
        • Texas Oncology - Baylor Charles A. Sammons Cancer Center
      • Tyler, Texas, United States, 75702
        • Texas Oncology P.A.
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age >/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.
  2. Documentation of triple negative breast cancer (estrogen and progesterone receptor <1% and HER2-negative)

  3. Prior systemic therapies (Cohort 1 only):

    1. No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
    2. Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
    3. Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.

  4. Prior systemic therapies (Cohort 2 only):

    1. Documentation of PD-L1 positive status
    2. 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.
  5. 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.
  6. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  8. Adequate organ function as demonstrated by normal laboratory values

Exclusion Criteria:

  1. Prior treatment with gemcitabine in any setting.

  2. 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.

  3. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
  4. Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.
  5. QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.
  6. Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol
  7. Pregnant or lactating women
  8. Prior hematopoietic stem cell or bone marrow transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Trilaciclib + gemcitabine + carboplatin
Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
Drug: Trilaciclib
Trilaciclib administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.
Other Names:
  • G1T28
  • COSELA
Drug: Gemcitabine
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle.
Drug: Carboplatin
Carboplatin administered IV on Day 1 and Day 8 of each 21-day cycle.
Placebo Comparator: Placebo + gemcitabine + carboplatin
The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
Drug: Gemcitabine
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle.
Drug: Carboplatin
Carboplatin administered IV on Day 1 and Day 8 of each 21-day cycle.
Drug: Placebo
Placebo administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.
Other Names:
  • 0.9% normal saline
  • 5 % Dextrose in water (D5W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect on Overall Survival (OS)
Time Frame: Cohort 1:From date of randomization up to 39 months
(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)
Time Frame: Cohort 2: From date of randomization up to 28 months
(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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life/Effects On Chemotherapy-Induced Fatigue
Time Frame: Cycle 1 Day 1 (each cycle is 21 days) up to 14 months
To assess the effect of trilaciclib on patients' quality of life as measured by time to first confirmed deterioration of fatigue compared with placebo in patients receiving gemcitabine and carboplatin
Cycle 1 Day 1 (each cycle is 21 days) up to 14 months
Myeloprotective Effects
Time Frame: Cycle 1 Day 1 (each cycle is 21 days) up to 14 months
Occurrence of cytopenias, febrile neutropenia, hospitalization due to chemotherapy-induced myelosuppression, RBC and platelet transfusions, growth factor administration, and dose reductions and delays
Cycle 1 Day 1 (each cycle is 21 days) up to 14 months
Progression Free Survival
Time Frame: From date of randomization up to 14 months)
To evaluate the effect of trilaciclib on progression-free survival (PFS) compared with placebo in patients receiving gemcitabine and carboplatin.
From date of randomization up to 14 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

G1 Therapeutics, Inc.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 14, 2021

Primary Completion (Actual)

May 24, 2024

Study Completion (Actual)

May 24, 2024

Study Registration Dates

First Submitted

February 18, 2021

First Submitted That Met QC Criteria

March 11, 2021

First Posted (Actual)

March 16, 2021

Study Record Updates

Last Update Posted (Actual)

August 1, 2024

Last Update Submitted That Met QC Criteria

July 31, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • G1T28-208
  • 2020-004930-39 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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