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Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC): (PRESERVE1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04607668
Recruitment Status : Terminated (Despite achieving co-primary endpoints & other secondary measures of myeloprotection & tolerability, early anti-tumor efficacy data favor patients receiving placebo. Given the low likelihood of achieving PFS & OS endpoints, G1 decided to discontinue)
First Posted : October 29, 2020
Last Update Posted : April 7, 2023
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Myelosuppression-Adult Chemotherapeutic Toxicity Drug: Trilaciclib Drug: Placebo Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 326 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double-Blinded Trial
Primary Purpose: Treatment
Official Title: PRESERVE 1: A Phase 3 Randomized, Double-blind Trial of Trilaciclib Versus Placebo in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer
Actual Study Start Date : October 16, 2020
Actual Primary Completion Date : February 13, 2023
Actual Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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%)


Outcome Measures
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Primary Outcome Measures :
  1. Myelopreservation [ Time Frame: Through Induction Period- on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab ]
    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 :
  1. Quality of Life/ Effects on Chemotherapy-Induced Fatigue [ Time Frame: Through Induction Period- on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab ]
    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).

  2. 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 ]
    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

  3. Anti-tumor Efficacy [ Time Frame: From date of randomization until date of death due to any cause ]
    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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 >.
  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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04607668


Locations
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Sponsors and Collaborators
G1 Therapeutics, Inc.
Investigators
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Study Director: Clinical Contact G1 Therapeutics, Inc.
More Information
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Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04607668    
Other Study ID Numbers: G1T28-207
First Posted: October 29, 2020    Key Record Dates
Last Update Posted: April 7, 2023
Last Verified: April 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by G1 Therapeutics, Inc.:
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
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
 Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases