Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC): (PRESERVE1)
Colorectal Cancer Metastatic, Myelosuppression-Adult, Chemotherapeutic Toxicity
About this trial
This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring 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
Eligibility Criteria
Selected Inclusion Criteria:
- 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 >.
- 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.
- Unresectable and measurable or evaluable disease 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.
- Adequate organ function
Selected Exclusion Criteria:
- 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
- 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)
- Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation
Sites / Locations
- AZ Oncology Associates - HOPE
- Beverly Hills Cancer Center
- Keck Medical Center of USC Pasadena
- The Oncology Institute of Hope & Innovation\ Innovative Clinical Research Institute
- Georgetown University - Lombardi Comprehensive Cancer Center
- Florida Cancer Specialists (South Region)
- Florida Cancer Specialists NORTH
- Mid-Florida Hematology & Oncology Centers, P.A.
- Florida Cancer Specialists
- Florida Cancer Specialists - Panhandle
- Northside Hospital - Georgia Cancer Specialists
- Illinois Cancer Specialists
- Boston Medical Center
- University of Massachusetts Memorial Medical Center
- Mayo Clinic - Rochester
- Comp. Cancer Centers of Nevada
- University of Oklahoma Health Sciences Center
- Oregon Health & Science University
- Gettysburg Cancer Center
- Tennessee Oncology
- UT Southwestern Medical Center
- Millennium Oncology
- Inova Schar Cancer Institute
- Onc and Hem Assoc of SW VA
- Henan Cancer Hospital
- Wuhan Union Hospital
- Jilin Provincial Tumor Hospital
- The First Affiliated Hospital of Zhejiang University
- Zhejiang Cancer Hospital
- The Affiliated Tumor Hospital of Harbin Medical University
- Jinan Central hospital
- Zhongshan Hospital Fudan University
- Xuzhou Central hospital
- First Affiliated Hospital of Zhengzhou University
- Orszagos Onkologiai Intezet
- Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
- Bacs-Kiskun Megyei Oktatokorhaz
- SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
- ASL Regionale Piemonte - Ospedale Santo Spirito Casale Monferrato (Ospedale di Casale Monferrato)
- Azienda Ospedaliera Universitaria Policlinico Tor Vergata
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
- Azienda Ospedaliera Universitaria Careggi
- Szpitale Pomorskie spółka z ograniczoną odpowiedzialnością
- Szpital Specjalistyczny im. L.Rydygiera w Krakowie
- Mrukmed Lekarz Beata Madej Mruk i Partner Spółka Partnerska Oddział nr 1 w Rzeszowie
- Centrum Medyczne Pratia Poznan
- Centrum Zdrowia MDM
- Hospital Universitari Vall d'Hebron
- Hospital Clinic de Barcelona
- ICO l'Hospitalet - Hospital Duran i Reynals
- Hospital Universitari Arnau de Vilanova
- Hospital Universitario Lucus Augsti
- Hospital General Universitario Gregorio Marañon
- Hospital Universitario Ramon y Cajal
- Hospital Universitario 12 de Octubre
- Hospital Universitario La Paz
- Hospital Universitario HM Madrid Sanchinarro
- Hospital Universitario Puerta de Hierro Majadahonda
- Hospital Universitario Virgen Macarena
- Hospital Universitario Virgen del Rocio
- Hospital Clinico Universitario de Valencia
- Hospital Universitario Miguel Servet
- CI Cherkasy Regional Oncological Dispensary of CRC
- MI Regional Clinical Oncologycal Dispensary
- Dnipropetrovsk City Multispecialty Clinical Hospital #4
- Limited Liability Company "Medical Center named by Academician Yuriy Prokopovich Spizhenko"
- CNE Prof. O.O. Shalimov Kharkiv City Clinical Hospital #2 of KCC
- Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU
- Treatment-Diagnostic Center of Private Enterprise of PPC Atsynus
- CI Kryvyi Rih Oncological Dispensary of DRC
- Medical Center Asklepion LLC
- Medical Center of Limited Liability Company Medical Center Concilium Medical
- Communal Enterprise Volyn Regional Medical Center of Oncology of Volyn Regional Council
- Communal Institution Odesa Regional Clinical Hospital; Department of Surgery
- University Hospital of Sumy State University
- CNE CCCH of Uzh CC Oncological Center, Ther Dept, SHEI UNU
- Medical center "Oncolife" LLC
- Barts Hospital
- Royal Free Hospital
- The Christie
- Velindre Cancer Centre
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
trilaciclib + FOLFOXIRI/bevacizumab
placebo + 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.
The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib