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

NCT04607668 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: G1T28-207
• Study Type: interventional
• Target: 326
• Locations: 8 countries
• Sites: 82

Brief Summary

This was 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.

Conditions

Colorectal Cancer Metastatic; Myelosuppression-Adult; Chemotherapeutic Toxicity

Keywords

Colorectal Cancer; mCRC; colon; chemotherapy-induced myelosuppression; chemotherapy-induced neutropenia; chemotherapy-induced anemia; CDK 4/6 inhibitor; trilaciclib; FOLFOXIRI; bevacizumab; myelosuppression; cyclin-dependent kinase 4/6 inhibitor; myelopreservation; rectum; Preserve; PRESERVE 1

Outcome Measures

Primary Outcomes (2)

• Duration of Severe Neutropenia (DSN)

  The DSN was defined as the number of days for the first severe neutropenia (SN) event in Cycles 1, 2, 3, or 4 for participants who had at least one SN event in the first 4 cycles of Induction. It was calculated as the days from the date of the first absolute neutrophil count (ANC) value of \< 0.5 × 10\^9/L to the date of the first ANC value ≥ 0.5 × 10\^9/L where no additional ANC values \< 0.5 × 10\^9/L were observed for the remainder of that cycle.

  Cycles 1 to 4 (14-day cycles up to 56 days)

• Occurrence of Severe Neutropenia (SN) During Induction

  Severe neutropenia was defined as the absolute neutrophil count (ANC) laboratory value that met the Common Terminology Criteria for Adverse vents (CTCAE) criteria for ≥ Grade 4 toxicity (ie, ANC \< 0.5 × 10\^9/L in SI Unit)

  Induction Period, cycles 1-12 (14-day cycles up to 168 days)

Secondary Outcomes (13)

• Overall Survival (OS)

  Up to 52 months

• Additional Myelopreservation Measures

  Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

• Red Blood Cell Lineage

  Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

• Platelet Lineage

  Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

• Multiple Lineage

  Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Study Arms (2)

trilaciclib + FOLFOXIRI/bevacizumab

EXPERIMENTAL

During Induction the following study drugs are administered on Day 1: Irinotecan - IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil - continuous infusion (CI) over 46 to 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 at study entry. Trilaciclib will be administered prior to infusional- 5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.

Drug: Trilaciclib

placebo + FOLFOXIRI/bevacizumab

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Trilaciclib DRUG

Trilaciclib diluted in dextrose 5% in water or normal saline (sodium chloride solution 0.9%) administered by IV infusion over approximately 30 (±10) minutes no more than 4 hours prior to each Day 1 chemotherapy administration. Second dose of trilaciclib was administered on Day 2.

Also known as: G1T28, CDK 4/6 inhibitor

trilaciclib + FOLFOXIRI/bevacizumab

Placebo DRUG

Dextrose 5% in water or normal saline (sodium chloride solution 0.9%) administered by IV infusion over 30 (±10) minutes no more than 4 hours prior to each Day 1 chemotherapy administration. Second dose of placebo was administered on Day 2.

placebo + FOLFOXIRI/bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \> 14.
• Unresectable and measurable or metastatic colorectal cancer per RECIST v1.1
• ECOG performance status of 0 to 1
• 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 (tissue requirements are provided in the associated laboratory manual).
• Hemoglobin ≥ 9.0 g/dL in the absence of RBC transfusion or ESA administration within 14 days prior to first dose of trilaciclib/placebo
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9 /L
• Platelet count ≥ 100 × 10\^9 /L
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/minute/1.73m\^2
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• AST, ALT, and alkaline phosphatase ≤ 3 × ULN for patients without liver or bone metastases; AST, ALT and alkaline phosphatase ≤ 5 × ULN in the presence of liver metastases; AST and ALT ≤ 3 x ULN and alkaline phosphatase ≤ 5 × ULN in the presence of bone metastases
• Resolution of nonhematologic toxicities from prior therapy or surgical procedures to ≤ Grade 1 or baseline (except alopecia)
• Urine dipstick protein \< 2+. If ≥ 2+ at Screening, then a 24-hour urine collection must be done to demonstrate ≤ 1 g of protein/24 hours
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Please see Section 17.4 for detailed instructions on methods of contraception requirements.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• 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.
• 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.
• 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.
• Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids (i.e., patient must be off steroids administered for brain metastases for at least 14 days prior to the first dose of trilaciclib/placebo).
• QTcF interval \> 450 msec (males) or \> 470 msec (females) at screening. For patients with ventricular pacemakers, QTcF \> 500 msec.
• Personal or family history of long QT syndrome
• Symptomatic peripheral neuropathy
• History of interstitial lung disease (ILD)
• Uncontrolled hypertension (blood pressure ≥ 150/90mm Hg)
• Clinically significant (i.e., active) cardiovascular disease at the time of signing the informed consent; for example cerebrovascular accidents (≤ 6 months before the first dose of trilaciclib/placebo), myocardial infarction (≤ 6 months before the first dose of trilaciclib/placebo), unstable angina, serious cardiac arrhythmia requiring medication, or uncontrolled symptomatic congestive heart failure \[Class II or higher as defined by the New York Heart Association \[NYHA\] functional classification system\])
• Serious, non-healing wound, ulcer, or bone fracture
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
• Known serious active infection (e.g., human immunodeficiency virus \[HIV\], hepatitis B or C, tuberculosis, etc.)
• Known Gilbert's Syndrome or homozygous for the UGT1A1\*28 allele. UGT1A1 genotyping is not required for this study.
• Chronic inflammatory bowel disease and/or active intestinal obstruction. Patients should not be treated until the intestinal obstruction has resolved.

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (82)

AZ Oncology Associates - HOPE

Tucson, Arizona, 85711, United States

Location

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

Keck Medical Center of USC Pasadena

Los Angeles, California, 90033, United States

Location

The Oncology Institute of Hope & Innovation\ Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Georgetown University - Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists (South Region)

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists NORTH

Fort Myers, Florida, 33916, United States

Location

Mid-Florida Hematology & Oncology Centers, P.A.

Orange City, Florida, 32763, United States

Location

Florida Cancer Specialists

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists - Panhandle

Tallahassee, Florida, 32308, United States

Location

Northside Hospital - Georgia Cancer Specialists

Atlanta, Georgia, 30342, United States

Location

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Comp. Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Millennium Oncology

Kingswood, Texas, 77339, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Onc and Hem Assoc of SW VA

Roanoke, Virginia, 24014, United States

Location

Henan Cancer Hospital

Zijingshan, Henan, China

Location

Wuhan Union Hospital

Wuhan, Hubei, China

Location

Jilin Provincial Tumor Hospital

Changchun, Jilin, China

Location

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Location

The Affiliated Tumor Hospital of Harbin Medical University

Heilongjiang, China

Location

Jinan Central hospital

Shandong, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Xuzhou Central hospital

Xuzhou, China

Location

First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza

Gyula, 5700, Hungary

Location

Bacs-Kiskun Megyei Oktatokorhaz

Kecskemét, 6000, Hungary

Location

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, 4400, Hungary

Location

ASL Regionale Piemonte - Ospedale Santo Spirito Casale Monferrato (Ospedale di Casale Monferrato)

Casale Monferrato, Alessandria, 15033, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Rome, Roma, 00133, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Roma, 00168, Italy

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Cremona, 26100, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50141, Italy

Location

Szpitale Pomorskie spółka z ograniczoną odpowiedzialnością

Gdynia, 81-519, Poland

Location

Szpital Specjalistyczny im. L.Rydygiera w Krakowie

Krakow, 31-637, Poland

Location

Mrukmed Lekarz Beata Madej Mruk i Partner Spółka Partnerska Oddział nr 1 w Rzeszowie

Rzeszów, 35-922, Poland

Location

Centrum Medyczne Pratia Poznan

Skórzewo, 60-185, Poland

Location

Centrum Zdrowia MDM

Warsaw, 00-635, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

ICO l'Hospitalet - Hospital Duran i Reynals

Barcelona, 08907, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital Universitario Lucus Augsti

Lugo, 27003, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario HM Madrid Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, 28222, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

CI Cherkasy Regional Oncological Dispensary of CRC

Cherkasy, 18009, Ukraine

Location

MI Regional Clinical Oncologycal Dispensary

Dnipro, 49100, Ukraine

Location

Dnipropetrovsk City Multispecialty Clinical Hospital #4

Dnipro, 49102, Ukraine

Location

Limited Liability Company "Medical Center named by Academician Yuriy Prokopovich Spizhenko"

Kapitanivka, 8112, Ukraine

Location

CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC

Kharkiv, 61037, Ukraine

Location

Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU

Kharkiv, 61070, Ukraine

Location

Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus

Kropyvnytskyi, Ukraine

Location

CI Kryvyi Rih Oncological Dispensary of DRC

Kryvyi Rih, 50048, Ukraine

Location

Medical Center Asklepion LLC

Kyiv, Ukraine

Location

Medical Center of Limited Liability Company Medical Center Concilium Medical

Kyiv, Ukraine

Location

Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council

Lutsk, 43018, Ukraine

Location

Communal Institution Odesa Regional Clinical Hospital; Department of Surgery

Odesa, 65025, Ukraine

Location

University Hospital of Sumy State University

Sumy, 40022, Ukraine

Location

CNE CCCH of Uzh CC Oncological Center, Ther Dept, SHEI UNU

Uzhhorod, Ukraine

Location

Medical center "Oncolife" LLC

Zaporizhzhia, 69059, Ukraine

Location

Barts Hospital

London, Greater London, EC1A 7BE, United Kingdom

Location

Royal Free Hospital

London, Greater London, NW3 2QG, United Kingdom

Location

The Christie

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Velindre Cancer Centre

Cardiff, South Glamorgan, CF14 2TL, United Kingdom

Location

Related Publications (1)

• Lenz HJ, Liu T, Chen EY, Horvath Z, Bondarenko I, Danielewicz I, Ghidini M, Garcia-Alfonso P, Jones R, Aapro M, Zhang Y, Wang J, Wang W, Adeleye J, Beelen A, Hubbard J. Trilaciclib prior to FOLFOXIRI/bevacizumab for patients with untreated metastatic colorectal cancer: phase 3 PRESERVE 1 trial. JNCI Cancer Spectr. 2025 Jan 3;9(1):pkae116. doi: 10.1093/jncics/pkae116.

  PMID: 39579142 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

trilaciclib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Clinical Trial Info
• Organization: G1 Therapeutics, Inc

clinicalinfo@g1therapeutics.com

+1 9192139835

Study Officials

• Clinical Contact

  G1 Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-Blinded Trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: October 29, 2020
• Study Start: January 6, 2021
• Primary Completion: February 13, 2023
• Study Completion: March 31, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

PL (5); ES (15); IT (5); CN (10); GB (4); UA (15); US (24); HU (4)