Clinical Trials /

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

NCT04607668

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Enrolling by invitation

Phase:

Phase 3

Trial Eligibility

Document

Title

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

  • ORG STUDY ID: G1T28-207
  • NCT ID: NCT04607668

Conditions

  • Colorectal Cancer Metastatic
  • Myelosuppression Adult
  • Chemotherapeutic Toxicity

Interventions

DrugSynonymsArms
TrilaciclibG1T28, CDK 4/6 inhibitortrilaciclib + FOLFOXIRI/bevacizumab
Placeboplacebo + FOLFOXIRI/bevacizumab

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
trilaciclib + FOLFOXIRI/bevacizumabExperimentalDuring 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.
  • Trilaciclib
placebo + FOLFOXIRI/bevacizumabPlacebo ComparatorThe subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib
  • Placebo

Eligibility Criteria

        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 >
             14.

          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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Myelopreservation
Time Frame:Through Induction Period- on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab
Safety Issue:
Description: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

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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:G1 Therapeutics, Inc.

Trial 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

Last Updated

October 23, 2020