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

Colorectal Cancer Metastatic Clinical Trial

— PRESERVE1  

Official title:

PRESERVE 1: A Phase 3 Randomized, Double-blind Trial of Trilaciclib Versus Placebo in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04607668
• Other study ID #: G1T28-207
• Status: Terminated
• Phase: Phase 3
• Start date: October 16, 2020
• Est. completion date: March 31, 2023

Study information

• Verified date: April 2023
• Source: G1 Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 326
• Est. completion date: March 31, 2023
• Est. primary completion date: February 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chemotherapeutic Toxicity
• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Myelosuppression-Adult

Intervention

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

Locations

Country	Name	City	State
China	Jilin Provincial Tumor Hospital	Changchun	Jilin
China	The First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	The Affiliated Tumor Hospital of Harbin Medical University	Heilongjiang
China	Jinan Central hospital	Shandong
China	Zhongshan Hospital Fudan University	Shanghai
China	Wuhan Union Hospital	Wuhan	Hubei
China	Xuzhou Central hospital	Xuzhou
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou
China	Henan Cancer Hospital	Zijingshan	Henan
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza	Gyula
Hungary	Bacs-Kiskun Megyei Oktatokorhaz	Kecskemet
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza
Italy	ASL Regionale Piemonte - Ospedale Santo Spirito Casale Monferrato (Ospedale di Casale Monferrato)	Casale Monferrato	Alessandria
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Cremona
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Rome	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Roma
Poland	Szpitale Pomorskie spólka z ograniczona odpowiedzialnoscia	Gdynia
Poland	Szpital Specjalistyczny im. L.Rydygiera w Krakowie	Krakow
Poland	Mrukmed Lekarz Beata Madej Mruk i Partner Spólka Partnerska Oddzial nr 1 w Rzeszowie	Rzeszów
Poland	Centrum Medyczne Pratia Poznan	Skórzewo
Poland	Centrum Zdrowia MDM	Warszawa
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	Barcelona
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital Universitario Lucus Augsti	Lugo
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Madrid Sanchinarro	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Ukraine	CI Cherkasy Regional Oncological Dispensary of CRC	Cherkasy
Ukraine	Dnipropetrovsk City Multispecialty Clinical Hospital #4	Dnipro
Ukraine	MI Regional Clinical Oncologycal Dispensary	Dnipro
Ukraine	Limited Liability Company "Medical Center named by Academician Yuriy Prokopovich Spizhenko"	Kapitanivka
Ukraine	CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC	Kharkiv
Ukraine	Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU	Kharkiv
Ukraine	Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus	Kropyvnytskyi
Ukraine	CI Kryvyi Rih Oncological Dispensary of DRC	Kryvyi Rih
Ukraine	Medical Center Asklepion LLC	Kyiv
Ukraine	Medical Center of Limited Liability Company Medical Center Concilium Medical	Kyiv
Ukraine	Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council	Lutsk
Ukraine	Communal Institution Odesa Regional Clinical Hospital; Department of Surgery	Odesa
Ukraine	University Hospital of Sumy State University	Sumy
Ukraine	CNE CCCH of Uzh CC Oncological Center, Ther Dept, SHEI UNU	Uzhgorod
Ukraine	Medical center "Oncolife" LLC	Zaporizhzhia
United Kingdom	Velindre Cancer Centre	Cardiff	South Glamorgan
United Kingdom	Barts Hospital	London	Greater London
United Kingdom	Royal Free Hospital	London	Greater London
United Kingdom	The Christie	Manchester	Greater Manchester
United States	Illinois Cancer Specialists	Arlington Heights	Illinois
United States	Northside Hospital - Georgia Cancer Specialists	Atlanta	Georgia
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Boston Medical Center	Boston	Massachusetts
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Florida Cancer Specialists (South Region)	Fort Myers	Florida
United States	Florida Cancer Specialists NORTH	Fort Myers	Florida
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Millennium Oncology	Kingswood	Texas
United States	Comp. Cancer Centers of Nevada	Las Vegas	Nevada
United States	Keck Medical Center of USC Pasadena	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Mid-Florida Hematology & Oncology Centers, P.A.	Orange City	Florida
United States	Oregon Health & Science University	Portland	Oregon
United States	Onc and Hem Assoc of SW VA	Roanoke	Virginia
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	Florida Cancer Specialists - Panhandle	Tallahassee	Florida
United States	AZ Oncology Associates - HOPE	Tucson	Arizona
United States	Georgetown University - Lombardi Comprehensive Cancer Center	Washington	District of Columbia
United States	The Oncology Institute of Hope & Innovation\ Innovative Clinical Research Institute	Whittier	California
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
G1 Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  China,  Hungary,  Italy,  Poland,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myelopreservation	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	Through Induction Period- on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab
Secondary	Quality of Life/ Effects on Chemotherapy-Induced Fatigue	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).	Through Induction Period- on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab
Secondary	Anti-tumor Efficacy	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	From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first
Secondary	Anti-tumor Efficacy	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	From date of randomization until date of death due to any cause