We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Docetaxel for Metastatic Non-Small Cell Lung Cancer (NSCLC) (PRESERVE 4) (PRESERVE 4)

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: NCT04863248
Recruitment Status : Terminated (Treatment paradigm in second- and third-line NSCLC is shifting away from docetaxel, the backbone chemotherapy therapy used in this study.)
First Posted : April 28, 2021
Last Update Posted : March 2, 2022
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

Brief Summary:
This is a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 trial evaluating the effect of trilaciclib on overall survival when administered prior to docetaxel in patients with mNSCLC treated in the 2nd or 3rd line setting.

Condition or disease Intervention/treatment Phase
Metastatic Non-Small Cell Lung Cancer NSCLC Lung Cancer Drug: Trilaciclib Drug: Placebo Drug: Docetaxel Phase 2

Detailed Description:

Patients must have documented disease progression during or after one or two lines of systemic therapy for recurrent or metastatic NSCLC. Prior treatment must have included, either in the same line or as separate lines of therapy: 1) a maximum of 1 line of platinum-containing chemotherapy for recurrent/metastatic disease and 2) a maximum of 1 line of a locally approved/authorized programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) containing regimen for recurrent/metastatic disease.

Patients will be randomly assigned (1:1) to receive trilaciclib or placebo intravenously (IV) prior to docetaxel on Day 1 of each 21-day cycle.

The study will include a screening phase, a treatment phase and a survival follow-up phase. 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Double-blind, Clinical Trial of Trilaciclib Versus Placebo in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) Treated With Docetaxel in the 2nd/3rd Line Setting (PRESERVE 4)
Actual Study Start Date : April 16, 2021
Actual Primary Completion Date : February 2, 2022
Actual Study Completion Date : February 2, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: trilaciclib + docetaxel
Patients will receive trilaciclib administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle.
Drug: Trilaciclib
Trilaciclib administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.
Other Names:
  • COSELA
  • G1T28

Drug: Docetaxel
Docetaxel administered IV on Day 1 of each 21-day cycle.
Other Names:
  • Taxotere
  • Docefrez

Placebo Comparator: placebo + docetaxel
Patients will receive placebo administered IV prior to docetaxel administered IV on Day 1 of each 21-day cycle.
Drug: Placebo
Placebo administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.
Other Names:
  • 0.9% normal saline
  • 5 % Dextrose in water (D5W)

Drug: Docetaxel
Docetaxel administered IV on Day 1 of each 21-day cycle.
Other Names:
  • Taxotere
  • Docefrez




Primary Outcome Measures :
  1. Effect of trilaciclib on Overall Survival (OS) compared with placebo [ Time Frame: From the date of randomization to the date of death for patients who died in the study due to any cause, or to the last contact date known to be alive for those who survived as of the data cutoff date, assessed up to 30 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on overall survival (OS) in patients with metastatic NSCLC receiving docetaxel in the second or third line.


Secondary Outcome Measures :
  1. Effect of trilaciclib on Progression Free Survival (PFS) compared with placebo [ Time Frame: From date of randomization to the date of documented radiologic PD per RECIST v1.1 or date of death regardless of the cause, whichever comes first, for those who had the events. Otherwise, PFS is calculated per censoring rules, assessed up to 30 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on progression free survival (PFS) in patients with metastatic NSCLC receiving docetaxel in the second or third line.

  2. Effect of trilaciclib on other anti-tumor endpoints compared with placebo [ Time Frame: From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on objective response rate (ORR) and duration of objective response (DOR) in patients with metastatic NSCLC receiving docetaxel in the second or third line.

  3. Effect of trilaciclib on the neutrophil lineage compared with placebo [ Time Frame: From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on duration of severe (grade 4) neutropenia in cycle 1, occurrence of severe (grade 4) neutropenia, occurrence of febrile neutropenia AEs, and occurrence of granulocyte colony-stimulating factor (G-CSF) administration in patients with metastatic NSCLC receiving docetaxel in the second or third line.

  4. Effect of trilaciclib on the red blood cell (RBC) lineage compared with placebo [ Time Frame: From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence of grade 3 or 4 decreased hemoglobin laboratory values, red blood cell (RBC) transfusions on or after week 5 (occurrence and number of transfusions), occurrence of erythropoiesis stimulating agent (ESA) administration in patients with metastatic NSCLC receiving docetaxel in the second or third line.

  5. Effect of trilaciclib on the platelet lineage compared with placebo [ Time Frame: From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence of grade 3 or 4 decreased platelet count laboratory values and platelet transfusions (occurrence and number of transfusions) in patients with metastatic NSCLC receiving docetaxel in the second or third line.

  6. Effect of trilaciclib on chemotherapy dosing compared with placebo [ Time Frame: From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on all-cause dose reductions (occurrence and number of reductions) and all-cause cycle delays (occurrence and number of delays) in patients with metastatic NSCLC receiving docetaxel in the second or third line.

  7. Effect of trilaciclib on hospitalizations due to chemotherapy induced myelosuppression compared with placebo [ Time Frame: From randomization to the end of the last study treatment cycle (each cycle is 21 days), assessed up to 19 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence and number of hospitalizations due to chemotherapy induced myelosuppression in patients with metastatic NSCLC receiving docetaxel in the second or third line.

  8. Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 [ Time Frame: Time from date of first dose of trilaciclib/placebo and docetaxel through 30 days following the last dose of trilaciclib/placebo and docetaxel, assessed up to 30 months. ]
    To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence and severity of adverse events (AEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5, study treatment discontinuation due to adverse events (AEs), and trilaciclib adverse events of special interest (AESI) in patients with metastatic NSCLC receiving docetaxel in the second or third line.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years of age at the time of signing the informed consent.
  • Histologically or cytologically confirmed metastatic NSCLC (squamous or nonsquamous) with no known actionable driver mutations (ex. EGFR, ROS1, ALK).

    1. Patients must have had documented disease progression during or after 1 or 2 lines of systemic treatment for recurrent or metastatic disease.
    2. Two components of treatment must have been received in the same line or as separate lines of therapy: (i) a maximum of 1 line of platinum-containing chemotherapy regimen for recurrent/metastatic disease, and (ii) a maximum of 1 line of a locally approved/authorized PD-1/PD-L1 mAb containing regimen for recurrent/metastatic disease.
    3. Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate line of therapy. Maintenance therapy is defined as therapy given within 42 days after the last dose of platinum-based chemotherapy in patients with ongoing clinical benefit (complete response [CR], partial response [PR] or stable disease [SD]).
  • Measurable or non-measurable disease per RECIST v1.1.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
  • A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh biopsy) with an associated pathology report documenting NSCLC must be available to send to the Sponsor, within the specified timeframe, for planned retrospective biomarker analyses.
  • Adequate organ function defined by the normal laboratory values.

Exclusion Criteria:

  • Prior therapy with docetaxel.
  • Any contraindication to the administration of docetaxel at the discretion of the investigator.
  • Mixed NSCLC/SCLC, or lung tumors whose predominant histology is sarcomatoid, or neuroendocrine.
  • Any 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 prostate-specific antigen (PSA) persistence/recurrence without metastatic disease) within 3 weeks prior to the first dose of trilaciclib/placebo.
  • Any radiotherapy within 2 weeks prior to the first dose of trilaciclib/placebo.
  • Presence of central nervous system (CNS) metastases requiring immediate treatment with radiation therapy or steroids (i.e., patient must be off steroids administered for brain metastases for at least 14 days prior to the first dose of trilaciclib/placebo).
  • Presence of leptomeningeal disease.
  • Significant third-space fluid retention (ex. ascites or pleural effusion) not amenable to required repeat drainage.
  • QT corrected using Fridericia's formula (QTcF) interval >480 msec at screening (confirmed on repeat). For patients with ventricular pacemakers, QTcF >500 msec.
  • Symptomatic peripheral neuropathy.
  • History of interstitial lung disease (ILD).
  • Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation.

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): NCT04863248


Locations
Layout table for location information
United States, Arizona
Ironwood Cancer &Research Centers
Phoenix, Arizona, United States, 85028
United States, California
Valkyrie Clinical Trials
Los Angeles, California, United States, 90067
Desert Hematology Oncology Medical Group, Inc
Rancho Mirage, California, United States, 92270
Innovative Clinical Research Institute - Oncology
Whittier, California, United States, 90602
United States, Florida
Mid-Florida Hematology Oncology
Orange City, Florida, United States, 32763
United States, Indiana
Indiana University Health Goshen Cancer Center
Goshen, Indiana, United States, 46526
United States, Missouri
St. Louis Cancer Care, LLP
Bridgeton, Missouri, United States, 63044
United States, New Jersey
Summit Medical Group
Florham Park, New Jersey, United States, 07932
Regional Cancer Car Associates LLC
Little Silver, New Jersey, United States, 07739
United States, Pennsylvania
Gettysburg Cancer Center
Gettysburg, Pennsylvania, United States, 17325
United States, Tennessee
University of Tennessee Medical Center
Knoxville, Tennessee, United States, 37920
United States, Texas
Millennium Oncology
Houston, Texas, United States, 77090
Sponsors and Collaborators
G1 Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Director: Clinical Contact G1 Therapeutics, Inc.
Layout table for additonal information
Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04863248    
Other Study ID Numbers: G1T28-210
2021-000186-32 ( EudraCT Number )
First Posted: April 28, 2021    Key Record Dates
Last Update Posted: March 2, 2022
Last Verified: February 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by G1 Therapeutics, Inc.:
Trilaciclib
Lung Cancer
Non-Small Cell Lung Cancer
PRESERVE 4
CDK 4/6 Inhibitor
cyclin-dependent kinase 4/6 inhibitor
Preserve
NSCLC
solid tumors
chemotherapy
metastatic
myeloprotection
advanced
stage 4
lung
docetaxel
COSELA
G1T28
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action