Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC): (PRESERVE1)
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|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
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|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer Metastatic Myelosuppression-Adult Chemotherapeutic Toxicity||Drug: Trilaciclib Drug: Placebo||Phase 3|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||326 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Masking Description:||Double-Blinded Trial|
|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|
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.
Trilaciclib or placebo
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
dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
- 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
- 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).
- 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
- 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
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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
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
|Study Director:||Clinical Contact||G1 Therapeutics, Inc.|
|Responsible Party:||G1 Therapeutics, Inc.|
|Other Study ID Numbers:||
|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|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
CDK 4/6 inhibitor
cyclin-dependent kinase 4/6 inhibitor
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases