PRESERVE1: Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC):

Sponsor
G1 Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04607668
Collaborator
(none)
296
121
2
49.5
2.4
0

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, placebo-controlled, global, multicenter, Phase 3 trial evaluating the impact of trilaciclib on myelopreservation and anti-tumor efficacy when administered prior to FOLFOXIRI/bevacizumab in patients with pMMR/MSS mCRC who have not received systemic therapy for metastatic disease.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Patients will be randomly assigned (1:1) to receive placebo or trilaciclib on Days 1 and 2 administered intravenously (IV) prior to FOLFOXIRI/bevacizumab in 14-day cycles for up to 12 cycles (Induction).

Following completion of Induction, patients will continue in Maintenance, where they will receive trilaciclib or placebo per randomization allocation at study entry. Trilaciclib/placebo will be administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction. The patient may continue to receive treatment on study until disease progression, unacceptable toxicity, withdrawal of consent, discontinuation by Investigator, or the end of the trial, whichever occurs first. Treatment cycles will occur consecutively without interruption, except when necessary to manage toxicities or for administrative reasons.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
296 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
Double-Blinded Trial
Primary Purpose:
Treatment
Official Title:
PRESERVE 1: A Phase 3 Randomized, Double-blind Trial of Trilaciclib Versus Placebo in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer
Actual Study Start Date :
Oct 16, 2020
Anticipated Primary Completion Date :
Nov 25, 2022
Anticipated Study Completion Date :
Nov 30, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: trilaciclib + FOLFOXIRI/bevacizumab

During Induction the following study drugs are administered on Day 1: Irinotecan- IV Oxaliplatin - IV Leucovorin- IV Fluorouracil - continuous infusion (CI) over 48 hours beginning on Day 1; Bevacizumab - IV Following completion of Induction, patients will continue in Maintenance, where they will continue to receive trilaciclib per randomization allocation. Trilaciclib will be administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.

Drug: Trilaciclib
Trilaciclib or placebo
Other Names:
  • G1T28
  • CDK 4/6 inhibitor
  • Placebo Comparator: placebo + FOLFOXIRI/bevacizumab

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

    Drug: Placebo
    dextrose 5% in water or normal saline (sodium chloride solution 0.9%)

    Outcome Measures

    Primary Outcome Measures

    1. Myelopreservation [Through Induction Period- on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab]

      To assess the effects of trilaciclib on the neutrophil lineage compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCRC as measured by duration of severe [Grade 4] neutropenia [DSN] in Cycle 1 and occurrence of severe neutropenia [SN] during Induction

    Secondary Outcome Measures

    1. Quality of Life/ Effects on Chemotherapy-Induced Fatigue [Through Induction Period- on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab]

      To assess the effects of trilaciclib on chemotherapy-induced fatigue compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCRC, as measured by Time To First Confirmed Deterioration of Fatigue (TTCD-fatigue) during Induction, as measured by the FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue).

    2. Anti-tumor Efficacy [From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first]

      To assess the effect of trilaciclib on Progression Free Survival (PFS) compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCRC as measured by Radiographic PFS (per RECIST 1.1) and OS

    3. Anti-tumor Efficacy [From date of randomization until date of death due to any cause]

      To assess the effect of trilaciclib on Overall Survival (OS) compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCRC as measured by Radiographic PFS (per RECIST 1.1) and OS

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Selected Inclusion Criteria:
    1. Age ≥ 18 years of age at the time of signing the informed consent. Patients > 70 years of age must have a G8 Health State Screening Tool (geriatric screening tool) score >.

    2. Proficient mismatch repair/microsatellite stable (pMMR/MSS), histologically or cytologically-confirmed adenocarcinoma of the colon or rectum. Patients with any BRAF or KRAS mutation status are eligible.

    3. Unresectable and measurable or evaluable disease per RECIST v1.1

    4. ECOG performance status of 0 to 1

    5. A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh biopsy) with an associated pathology report documenting pMMR/MSS mCRC must be confirmed to be available to send to the Sponsor for planned retrospective biomarker analyses.

    6. Adequate organ function

    Selected Exclusion Criteria:
    1. Prior systemic therapy for mCRC. Patients who received adjuvant/neoadjuvant therapy (ie, treatment with curative intent) for colorectal cancer are eligible if it has been ≥ 6 months between the last dose of systemic chemotherapy and the date of informed consent.

    2. Any radiotherapy, chemotherapy, immunotherapy, biologic, investigational, or hormonal therapy for cancer treatment (except for adjuvant hormonal therapy for breast cancer or prostate cancer defined as M0 disease or PSA persistence/recurrence without metastatic disease) within 3 weeks prior to the first dose of trilaciclib/placebo.

    3. Receipt of any low-dose systemic chemotherapeutic agent (e.g., low-dose methotrexate for rheumatoid arthritis) administered for a nononcologic purpose within 3 weeks prior to the first dose of trilaciclib/placebo.

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

    5. QTcF interval > 450 msec (males) or > 470 msec (females) at screening. For patients with ventricular pacemakers, QTcF > 500 msec.

    6. Personal or family history of long QT syndrome

    7. Symptomatic peripheral neuropathy

    8. History of interstitial lung disease (ILD)

    9. Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 AZ Oncology Associates - HOPE Tucson Arizona United States 85711
    2 University of Arizona Cancer Center Tucson Arizona United States 85724
    3 Beverly Hills Cancer Center Beverly Hills California United States 90211
    4 Keck Medical Center of USC Pasadena Los Angeles California United States 90033
    5 The Oncology Institute of Hope & Innovation\ Innovative Clinical Research Institute Whittier California United States 90603
    6 University of Colorado Health - Memorial Hospital Colorado Springs Colorado United States 80909
    7 Georgetown University - Lombardi Comprehensive Cancer Center Washington District of Columbia United States 20007
    8 Florida Cancer Specialists (South Region) Fort Myers Florida United States 33916
    9 Florida Cancer Specialists NORTH Fort Myers Florida United States 33916
    10 Mayo Clinic in Florida Jacksonville Florida United States 32224
    11 Mid-Florida Hematology & Oncology Centers, P.A. Orange City Florida United States 32763
    12 Florida Cancer Specialists Saint Petersburg Florida United States 33705
    13 Florida Cancer Specialists - Panhandle Tallahassee Florida United States 32308
    14 AdventHealth Digest. Health Tampa Florida United States 33613
    15 Northside Hospital - Georgia Cancer Specialists Atlanta Georgia United States 30342
    16 Augusta University Augusta Georgia United States 30912
    17 Illinois Cancer Specialists Arlington Heights Illinois United States 60005
    18 Mary Bird Perkins Cancer Center Baton Rouge Louisiana United States 70809
    19 Boston Medical Center Boston Massachusetts United States 02118
    20 University of Massachusetts Memorial Medical Center Worcester Massachusetts United States 01655
    21 Mayo Clinic - Rochester Rochester Minnesota United States 55905
    22 St. Louis Cancer Care, LLP Bridgeton Missouri United States 63044
    23 Health Midwest Ventures Group, Inc d/b/a HCA MidAmerica Division, LLC Kansas City Missouri United States 64132
    24 Comp. Cancer Centers of Nevada Las Vegas Nevada United States 89169
    25 University of Rochester Medical Center Rochester New York United States 14642
    26 The Ohio State University Columbus Ohio United States 43210
    27 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    28 Oregon Health & Science University Portland Oregon United States 97239
    29 Gettysburg Cancer Center Gettysburg Pennsylvania United States 17325
    30 Tennessee Oncology Nashville Tennessee United States 37203
    31 Texas Oncology-Baylor Sammons Dallas Texas United States 75246
    32 UT Southwestern Medical Center Dallas Texas United States 75390
    33 Millennium Oncology Kingswood Texas United States 77339
    34 Inova Schar Cancer Institute Fairfax Virginia United States 22031
    35 Virginia Oncology Associates Newport News Virginia United States 23606
    36 Onc and Hem Assoc of SW VA Roanoke Virginia United States 24014
    37 Henan Cancer Hospital Zijingshan Henan China
    38 Wuhan Union Hospital Wuhan Hubei China
    39 Jilin Provincial Tumor Hospital Changchun Jilin China
    40 The First Affiliated Hospital of Zhejiang University Hangzhou Zhejiang China
    41 Zhejiang Cancer Hospital Hangzhou Zhejiang China
    42 The Affiliated Tumor Hospital of Harbin Medical University Heilongjiang China
    43 Jinan Central hospital Shandong China
    44 Zhongshan Hospital Fudan University Shanghai China 200032
    45 Xuzhou Central hospital Xuzhou China
    46 First Affiliated Hospital of Zhengzhou University Zhengzhou China
    47 Orszagos Onkologiai Intezet Budapest Hungary 1122
    48 Debreceni Egyetem Debrecen Hungary 4032
    49 Petz Aladar Megyei Oktato Korhaz Gyor Hungary 9024
    50 Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza Gyula Hungary 5700
    51 Bacs-Kiskun Megyei Oktatokorhaz Kecskemet Hungary 6000
    52 SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz Nyiregyhaza Hungary 4400
    53 Tolna Megyei Balassa Janos Korhaz Onkologiai Osztaly Szekszard Hungary 7100
    54 ASL Regionale Piemonte - Ospedale Santo Spirito Casale Monferrato (Ospedale di Casale Monferrato) Casale Monferrato Alessandria Italy 15033
    55 AOU Cagliari- P.O. Policlinico Universitario Duilio Casula Monserrato Cagliari Italy 90100
    56 IRCCS Centro di Riferimento Oncologico Aviano Pordenone Italy 33081
    57 Azienda Ospedaliera Universitaria Policlinico Tor Vergata Rome Roma Italy 00133
    58 Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Roma Italy 00168
    59 Ospedale P. Pederzoli - Casa di Cura Privata Spa Presidio Ospedaliero ULSS 9 - Scaligera Peschiera del Garda Verona Italy 37019
    60 Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico Cremona Italy 26100
    61 Azienda Ospedaliera Universitaria Careggi Firenze Italy 50141
    62 Azienda Ospedaliera Bianchi Melacrino Morelli Reggio Calabria Italy 89124
    63 Università Campus Bio-Medico di Roma Roma Italy 00128
    64 Bialostockie Centrum Onkologii im.M.Sklodowskiej-Curie Bialystok Poland 15-027
    65 Szpitale Pomorskie spółka z ograniczoną odpowiedzialnością Gdynia Poland 81-519
    66 Szpital Specjalistyczny im. L.Rydygiera w Krakowie Krakow Poland 31-637
    67 Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli Lublin Poland 20-090
    68 Mrukmed Lekarz Beata Madej Mruk i Partner Spółka Partnerska Oddział nr 1 w Rzeszowie Rzeszów Poland 35-922
    69 Centrum Medyczne Pratia Poznan Skórzewo Poland 60-185
    70 Pratia MCM Krakow Sucha Beskidzka Poland 34-200
    71 Centrum Zdrowia MDM Warszawa Poland 00-635
    72 Onkologicky ustav svatej Alzbety s.r.o. Bratislava Slovakia 55131
    73 Univerzitna nemocnica s poliklinikou, Milosrdni bratia, spol. s.r.o. Onkologicke oddelenie Bratislava Slovakia 81465
    74 Fakultna nemocnica s poliklinikou J.A. Reimana Presov Oddelenie klinickej onkologie Presov Slovakia 081 81
    75 Fakultna nemocnica s poliklinikou Zilina Zilina Slovakia
    76 Complejo Hospitalario Universitario de Orense Ourense Orense Spain 32005
    77 Hospital del Mar Barcelona Spain 08003
    78 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    79 Hospital Clinic de Barcelona Barcelona Spain 08036
    80 ICO l'Hospitalet - Hospital Duran i Reynals Barcelona Spain 08907
    81 Hospital Universitario Virgen de las Nieves Granada Spain 18014
    82 Hospital Universitari Arnau de Vilanova Lleida Spain 25198
    83 Hospital Universitario Lucus Augsti Lugo Spain 27003
    84 Hospital General Universitario Gregorio Marañon Madrid Spain 28007
    85 Hospital Universitario Ramon y Cajal Madrid Spain 28034
    86 Hospital Universitario 12 de Octubre Madrid Spain 28041
    87 Hospital Universitario La Paz Madrid Spain 28046
    88 Hospital Universitario HM Madrid Sanchinarro Madrid Spain 28050
    89 Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain 28222
    90 Hospital Regional Universitario de Malaga Malaga Spain 29010
    91 Hospital Universitario Virgen Macarena Sevilla Spain 41009
    92 Hospital Universitario Virgen del Rocio Sevilla Spain 41013
    93 Hospital Clinico Universitario de Valencia Valencia Spain 46010
    94 Hospital Universitario Miguel Servet Zaragoza Spain 50009
    95 CI Cherkasy Regional Oncological Dispensary of CRC Cherkasy Ukraine 18009
    96 MI Regional Clinical Oncologycal Dispensary Dnipro Ukraine 49100
    97 Dnipropetrovsk City Multispecialty Clinical Hospital #4 Dnipro Ukraine 49102
    98 CI Carpathian Clinical Oncological Center Ivano-Frankivsk Ukraine
    99 Limited Liability Company "Medical Center named by Academician Yuriy Prokopovich Spizhenko" Kapitanivka Ukraine 8112
    100 CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC Kharkiv Ukraine 61037
    101 Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU Kharkiv Ukraine 61070
    102 CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection Kharkiv Ukraine 61166
    103 Cne Kherson Reg Oncological Dispensary of Kherson Rc Kherson Ukraine
    104 Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus Kropyvnytskyi Ukraine
    105 CI Kryvyi Rih Oncological Dispensary of DRC Kryvyi Rih Ukraine 50048
    106 Kyiv Сity Clinical Oncological Center Kyiv Ukraine 03115
    107 Medical Center Asklepion LLC Kyiv Ukraine
    108 Medical Center of Limited Liability Company Medical Center Concilium Medical Kyiv Ukraine
    109 Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council Lutsk Ukraine 43018
    110 LISOD Hospital of Israeli Oncology Obukhiv Ukraine 08720
    111 Communal Institution Odesa Regional Clinical Hospital; Department of Surgery Odesa Ukraine 65025
    112 University Hospital of Sumy State University Sumy Ukraine 40022
    113 CNE CCCH of Uzh CC Oncological Center, Ther Dept, SHEI UNU Uzhgorod Ukraine
    114 Communal Enterprise Kremenchuk Regional Oncology Dispensary of Poltava Regional Council Zaporizhzhia Ukraine 39617
    115 CI Zaporizhzhia Regional Clinical Oncological Dispensary of ZRC Thoracic Department Zaporizhzhia Ukraine 69040
    116 Medical center "Oncolife" LLC Zaporizhzhia Ukraine 69059
    117 Torbay Hospital Torquay Devon United Kingdom TQ2 7AA
    118 Barts Hospital London Greater London United Kingdom EC1A 7BE
    119 Royal Free Hospital London Greater London United Kingdom NW3 2QG
    120 The Christie Manchester Greater Manchester United Kingdom M20 4BX
    121 Velindre Cancer Centre Cardiff South Glamorgan United Kingdom CF14 2TL

    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:
    NCT04607668
    Other Study ID Numbers:
    • G1T28-207
    First Posted:
    Oct 29, 2020
    Last Update Posted:
    Dec 27, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by G1 Therapeutics, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 27, 2021