PRESERVE1: Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC):
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 |
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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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
- 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
- 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).
- 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
- 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
Selected Inclusion Criteria:
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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 >.
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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.
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Unresectable and measurable or evaluable disease per RECIST v1.1
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ECOG performance status of 0 to 1
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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.
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Adequate organ function
Selected Exclusion Criteria:
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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.
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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.
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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.
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Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids
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QTcF interval > 450 msec (males) or > 470 msec (females) at screening. For patients with ventricular pacemakers, QTcF > 500 msec.
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Personal or family history of long QT syndrome
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Symptomatic peripheral neuropathy
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History of interstitial lung disease (ILD)
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Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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.- G1T28-207