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Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC) (PRESERVE 2)

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ClinicalTrials.gov Identifier: NCT04799249
Recruitment Status : Recruiting
First Posted : March 16, 2021
Last Update Posted : May 12, 2022
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

Study Description
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Brief Summary:
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of trilaciclib versus placebo administered prior to gemcitabine and carboplatin in patients receiving first- or second-line treatment for locally advanced unresectable/metastatic TNBC.

Condition or disease Intervention/treatment Phase
TNBC - Triple-Negative Breast Cancer Breast Cancer Drug: Trilaciclib Drug: Placebo Drug: Gemcitabine Drug: Carboplatin Phase 3

Detailed Description:

This study will have two separate cohorts (Cohort 1 and Cohort 2). Both cohorts will follow the same general study conduct/design with similar primary and key secondary endpoints and identical treatment arms.

  • Cohort 1 will evaluate patients receiving first-line therapy, regardless of programmed death-ligand 1 (PD-L1) status, who are programmed cell death protein 1 (PD-1)/PD-L1 inhibitor therapy naïve.
  • Cohort 2 will evaluate PD-L1 positive patients receiving second-line therapy following prior PD-1/PD-L1 inhibitor therapy in the locally advanced unresectable/metastatic setting.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double-Blind Trial
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind Study of Trilaciclib or Placebo in Patients Receiving First- or Second-Line Gemcitabine and Carboplatin Chemotherapy for Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (PRESERVE 2)
Actual Study Start Date : April 15, 2021
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : October 25, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Trilaciclib + gemcitabine + carboplatin
Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
 Drug: Trilaciclib
Trilaciclib administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.
Other Names:
  • G1T28
  • COSELA

Drug: Gemcitabine
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle.

Drug: Carboplatin
Carboplatin administered IV on Day 1 and Day 8 of each 21-day cycle.
Placebo Comparator: Placebo + gemcitabine + carboplatin
The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
 Drug: Placebo
Placebo administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.
Other Names:
  • 0.9% normal saline
  • 5 % Dextrose in water (D5W)

Drug: Gemcitabine
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle.

Drug: Carboplatin
Carboplatin administered IV on Day 1 and Day 8 of each 21-day cycle.


Outcome Measures
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Primary Outcome Measures :
  1. Effect on Overall Survival (OS) [ Time Frame: Cohort 1:From date of randomization up to 39 months ]
    (Cohort 1):To evaluate the effect of trilaciclib on overall survival (OS) compared with placebo in patients receiving first-line gemcitabine and carboplatin.

  2. Effect on Overall Survival (OS) [ Time Frame: Cohort 2: From date of randomization up to 28 months ]
    (Cohort 2): To evaluate the effect of trilaciclib on OS compared with placebo in patients receiving gemcitabine and carboplatin as second-line therapy after treatment with a PD-1/PD-L1 inhibitor in the locally advanced unresectable/metastatic setting


Secondary Outcome Measures :
  1. Quality of life/Effects On Chemotherapy-Induced Fatigue [ Time Frame: Cycle 1 Day 1 (each cycle is 21 days) up to 14 months ]
    To assess the effect of trilaciclib on patients' quality of life as measured by time to first confirmed deterioration of fatigue compared with placebo in patients receiving gemcitabine and carboplatin

  2. Myeloprotective Effects [ Time Frame: Cycle 1 Day 1 (each cycle is 21 days) up to 14 months ]
    Occurrence of cytopenias, febrile neutropenia, hospitalization due to chemotherapy-induced myelosuppression, RBC and platelet transfusions, growth factor administration, and dose reductions and delays

  3. Progression Free Survival [ Time Frame: From date of randomization up to 14 months) ]
    To evaluate the effect of trilaciclib on progression-free survival (PFS) compared with placebo in patients receiving gemcitabine and carboplatin.


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

Inclusion Criteria:

  1. Age >/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.
  2. Documentation of triple negative breast cancer (estrogen and progesterone receptor <1% and HER2-negative)

  3. Prior systemic therapies (Cohort 1 only):

    1. No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
    2. Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
    3. Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.

  4. Prior systemic therapies (Cohort 2 only):

    1. Documentation of PD-L1 positive status
    2. Treated with a PD-1/PD-L1 inhibitor for a minimum duration of 4 months in the locally advanced unresectable/metastatic setting and as the most recent therapy.
  5. Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Patients should be recovered from the effects of radiation.
  6. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  8. Adequate organ function as demonstrated by normal laboratory values

Exclusion Criteria:

  1. Prior treatment with gemcitabine in any setting.

  2. Prior treatment with carboplatin in the locally advanced unresectable/metastatic setting.

    Prior carboplatin in the (neo)adjuvant/curative setting is permitted as long as it was completed ≥ 6 months prior to the first metastatic recurrence.

  3. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
  4. Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.
  5. QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.
  6. Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol
  7. Pregnant or lactating women
  8. Prior 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): NCT04799249


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

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: NCT04799249    
Other Study ID Numbers: G1T28-208
2020-004930-39 ( EudraCT Number )
First Posted: March 16, 2021    Key Record Dates
Last Update Posted: May 12, 2022
Last Verified: May 2022

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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.:
breast cancer
gemcitabine
carboplatin
solid tumors
breast
chemotherapy
TNBC
trilaciclib
cyclin-dependent kinase 4/6 inhibitor
CDK 4/6 Inhibitor
triple-negative breast cancer
metastatic
 chemotherapy-induced fatigue
HER2-negative
immunotherapy
immune checkpoint inhibitor therapy
chemotherapy-induced myelosuppression
myeloprotection
myeloprotective
PD-1/PD-L1 inhibitor therapy
advanced
stage 4
preserve
PRESERVE 2
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Carboplatin
Antineoplastic Agents
 Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs