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

Sponsor
G1 Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04799249
Collaborator
(none)
250
Enrollment
112
Locations
2
Arms
42.3
Anticipated Duration (Months)
2.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
Double-Blind Trial
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Apr 15, 2021
Anticipated Primary Completion Date :
Jun 30, 2024
Anticipated Study Completion Date :
Oct 25, 2024

Arms and Interventions

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: 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)

    • 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.

    Outcome Measures

    Primary Outcome Measures

    1. Effect on Overall Survival (OS) [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.

    2. Effect on Overall Survival (OS) [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

    Secondary Outcome Measures

    1. Quality of life/Effects On Chemotherapy-Induced Fatigue [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

    2. Myeloprotective Effects [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

    3. Progression Free Survival [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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):

    4. No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.

    5. Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.

    6. Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.

    7. Prior systemic therapies (Cohort 2 only):

    8. Documentation of PD-L1 positive status

    9. 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.

    10. 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.

    11. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.

    12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    13. 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.

    1. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.

    2. Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.

    3. QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.

    4. Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol

    5. Pregnant or lactating women

    6. Prior hematopoietic stem cell or bone marrow transplantation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alabama Oncology Birmingham Alabama United States 35235
    2 Ironwood Cancer and Research Centers Chandler Arizona United States 85224
    3 3236-Banner M.D. Anderson Cancer Center Gilbert Arizona United States 85234
    4 Sansum Clinic Santa Barbara California United States 93105
    5 Washington Cancer Institute at MedStar Washington Hospital Center - Oncology Research Washington District of Columbia United States 20010
    6 Florida Cancer Specialists - North (SCRI) Saint Petersburg Florida United States 33705
    7 Moffitt Cancer Center Tampa Florida United States 33612
    8 Illinois Cancer Specialists Niles Illinois United States 60005
    9 University of Maryland Greenbaum Comprehensive Cancer Ctr-site# 1128 Baltimore Maryland United States 21021
    10 Maryland Oncology Hematology, P.A. Clinton Maryland United States 20735
    11 Saint Luke's Cancer Specialists Kansas City Missouri United States 64111
    12 Comprehensive Cancer Genetics of Nevada Las Vegas Nevada United States 89128
    13 Atrium Health Levine Cancer Institute Charlotte North Carolina United States 28204
    14 3312-Duke Cancer Center Durham North Carolina United States 27710
    15 Northwest Cancer Specialists, PC Portland Oregon United States 97225
    16 UPC Pinnacle Health Cancer Institute Pittsburgh Pennsylvania United States 15232
    17 Abington Hematology Oncology Willow Grove Pennsylvania United States 19090
    18 Tennessee Oncology Chattanooga Chattanooga Tennessee United States 37404
    19 Baptist Cancer Cancer - Oncology Memphis Tennessee United States 38120
    20 Tennessee Oncology (SCRI) Nashville Tennessee United States 37203
    21 Texas Oncology- Austin Central Austin Texas United States 78731
    22 Texas Oncology P.A. Dallas Texas United States 75231
    23 Texas Oncology-Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    24 Texas Oncology-West Texas El Paso Texas United States 79912
    25 Texas Oncology - Houston Memorial City Houston Texas United States 77024
    26 Texas Oncology P.A. Houston Texas United States 77070
    27 Texas Oncology Cancer Care and Research Center (site# 3317) Irving Texas United States 75063
    28 Texas Oncology P.A. Tyler Texas United States 75702
    29 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
    30 Virginia Oncology Associates Norfolk Virginia United States 23502
    31 (3151) 119-143 Missenden Road Camperdown New South Wales Australia 2050
    32 3138-Sunshine Coast University Hospital Birtinya Queensland Australia 4575
    33 3102-Peter MacCallum Cancer Centre - Oncology East Melbourne Victoria Australia 08006
    34 3150-Cabrini Malvern , Hospital Malvern Victoria Australia 3144
    35 3152 Mater Hospital Sydney North Sydney Australia 2060
    36 1239-Complex Oncology Center - Burgas Burgas Bulgaria 8000
    37 1320-Mhat Dr.Tota Venkova Gabrovo Bulgaria 5300
    38 1315-Medical Ctr Nadezhda Clinical Sofia Bulgaria 1330
    39 1258- Acibadem City Clinic Tokuda Sofia Bulgaria 1407
    40 3269-Anhui Provincial Hospital Hefei Anhui China 230001
    41 3266--Cancer Hospital Chinese Academy of Medical Sciences Chaoyang Beijing China 100021
    42 3274---The First Affiliated Hospital of Chongqing Medical University Yuzhong Chongqing China 401122
    43 3275-Sun Yat-sen University Cancer Center Yuexiu Guangzhou China 510060
    44 3272-The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China 050011
    45 3267__Harbin Medical University Cancer Hospital Harbin Heilongjiang China 150081
    46 3205-First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China 450052
    47 3268---Jiangsu Maternal Child Health Nanjing Jiangsu China 210000
    48 3270-- The First Hospital of Jilin University Changchun Jilin China 130021
    49 3276--Jilin Cancer Hospital Changchun Jilin China 130021
    50 3271---Tianjin Cancer Hospital Tianjin Tianjin China 300060
    51 3273--Zhejiang Cancer Hospital Hangzhou Zhejiang China 310022
    52 3339---No.270 Dong An Road Shanghai China 450052
    53 3124-Centre Francois Baclesse Caen Europe France 14000
    54 3123-Centre Jean Bernard Le Mans Europe France 72000
    55 3118-Centre Hospitalier de Poitiers Poitiers Europe France 86000
    56 3125-Centre Leon Berard Villejuif Europe France 94800
    57 3119-31 rue de la Croix Verte , ICM-Val d'Aurelle Montpellier France 34298
    58 3120--Serv Pharmacie Recherche Clin Nantes France 44000
    59 3122-Pharmacie Essais Cliniques Toulouse France 31100
    60 3113-LTD"Brothers" Batumi Ajaria Georgia 6010'
    61 2822-"High Technology Hospital MedCenter" LTD Batumi Ajaria Georgia 6010
    62 1107-ARENSIA Exploratory Medicine Harmony Health Tbilisi Georgia 0112
    63 3126-Acad.Fridon Todua Medical Center- Research Institute of Clinical Medicine Tbilisi Georgia 0112
    64 3127- LTDIsraeli-Georgian Medical Research Clinic Helsicore Tbilisi Georgia 0112
    65 3362-"Pineo Medical Ecosystem"LTD Tbilisi Georgia 0114
    66 1255-Ljubljana Str "Tbilisi Cancer Center" LTD Tbilisi Georgia 0159
    67 3337-LTD S.Khechinashvili University Hospital Tbilisi Georgia 0179
    68 1256-Institute for Personalized Medicine LTD (site #-1256) Tbilisi Georgia 0186
    69 3111-Consilium Medulla , Multiprofile Clinic Tbilisi Georgia 0186
    70 3363-"TIM - Tbilisi Institute of Medicine" LTD Tbilisi Georgia 0186
    71 3112-LTD "Institute Of Clinical Oncology" Tbilisi Georgia 159
    72 1310_IMSP Institutul Oncologic, ARENSIA Exploratory Medicine Chisinau Moldova, Republic of MD-2025
    73 3146-Pratia MCM Krakow Krakow Malopolskie Poland 30-510
    74 1314-MED-POLONIA Sp.z o.o. Poznan Wielkopolskie Poland 60-569
    75 3147-M.Kopernika.w.Lodzi Lodz Poland 93-513
    76 2709-Centrum Medyczne Pratia Poznan Skorzewo Poland 60-185
    77 3149 NarodowyInstytutiiMariiCurie Warszawa Poland 02-781
    78 3354-Wojewodzki Szpital Specjali. , Wroclawiu Apteka Szpitalna , ul. H. M. Kamienskiego 73a Wroclaw Poland 51-124
    79 1311-Instytut MSF Sp. z. o.o. Łódź Poland 90-302
    80 3133-City Clinical Oncology Dispensary Moscow Balashikha Russian Federation 143900
    81 3116-Moscow City Oncology Hospital #62 Moscow Krasnogorsk Russian Federation 143423
    82 3132-Leningrad Regional Clinical Oncology Dispensary Moscow Vsevolozhsky Russian Federation 188663
    83 3114- Rep Clinical Onco. Disp. Mini Kazan Russian Federation 420029
    84 3166-FSBI Ru.Sci Roentgenoradiol. Moscow Russian Federation 117997
    85 3135-University Clinic of Headaches Moscow Russian Federation 121467
    86 3134-Moscow Regional Oncology Dispensary Moscow Russian Federation 143900
    87 3115-Mikhail Dvorkin, MD Omsk Russian Federation 644013
    88 3136--LLC Clinic "Luch" Saint-Petersburg, Russian Federation 197110
    89 1153-Clinical Hospital Center "Bezanijska Kosa", Oncology Clinic Belgrade Serbia 11000
    90 1171-Special hospital for Internal diseases Oncomed system, Karposeva 91, Belgrade Serbia 11000
    91 3101-Institute for Oncology and Radiology of Serbia Belgrade Serbia 11000
    92 1155-University Clinical Center Nis, Oncology Clinic Nis Serbia 18000
    93 1156- Oncology Institute of Vojvodina, Clinic for internal oncology Sremska Kamenica Serbia 21204
    94 3139---H.G.U. de Elche Elche Alicante Spain 03203
    95 3154----Hospital Universitario Virgen del Rocío Avenida Manuel Siurot s/n Sevilla Andalucía Spain 41013
    96 3343-Hospital Puerta de Hierro Madrid Majadahonda Spain 28222
    97 3342-Hospit.Universit.Infanta, Cristina Servicio Farmacia Planta Badajoz Spain 06006
    98 3142__Hospital Univ Vall d'Hebrón Barcelona Spain 08035
    99 3144__Hospital Universitario 12 de Octubre Barcelona Spain 08035
    100 3141---Hospital Clìnic de Barcelona Barcelona Spain 08036
    101 3143--Hospital Universitari General de Catalunya Servicio de Oncologia Barcelona Spain 08190
    102 3155__Hospital Univ Ramón y Cajal Madrid Spain 28034
    103 3347-Hospital Universitari Son Palma de Mallorca Spain 07120
    104 3140--Hosp Virgen de la Macarena Sevilla Spain 41009
    105 2807--Dniprovske shose Kryvyi Rih Dnipropetrovska Ukraine 50048
    106 2808--ARENSIA Exploratory Medicine Kapitanivka Kyivska Oblast Ukraine 08112
    107 1251---Sumskyi obl. klinichnyi onkol. Sumy Sums'ka Oblast Ukraine 40022
    108 1250--"Ternopil obl klin onkodyspanser" TOR Ternopil Ternopil's'ka Oblast Ukraine 46023
    109 3161-Podilskyi rehionalnyi tsentr onkolohii, viddilennia khimioterapii Vinnytsia Vinnyts'ka Oblast Ukraine 21029
    110 1249---KP "Volynskyi obl med tsentr onkolohii" VOR Lutsk Volyns'ka Oblast Ukraine 63000
    111 1246-Komissiia z pytan Dnipro Ukraine 49102
    112 2806---Zaporizhzhia Regional Antitumor Center Zaporizhzhia Ukraine 69040

    Sponsors and Collaborators

    • G1 Therapeutics, Inc.

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    G1 Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT04799249
    Other Study ID Numbers:
    • G1T28-208
    • 2020-004930-39
    First Posted:
    Mar 16, 2021
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by G1 Therapeutics, Inc.
    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
    Additional relevant MeSH terms:
    Breast Neoplasms
    Triple Negative Breast Neoplasms
    Gemcitabine
    Carboplatin

    Study Results

    No Results Posted as of Aug 2, 2022