Purpose

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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)
Masking Description
Double-Blinded Trial

Arm Groups

ArmDescriptionAssigned Intervention
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%)

Recruiting Locations

Boston Medical Center
Boston, Massachusetts 02118
Contact:
Thomas Medina
617-638-6256
thomas.medina@bmc.org

More Details

Status
Recruiting
Sponsor
G1 Therapeutics, Inc.

Study Contact

G1Therapeutics Clinical Contact
919-213-9835
clinicalinfo@g1therapeutics.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.