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

Sponsor
G1 Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04799249
Collaborator
(none)
250
Enrollment
29
Locations
2
Arms
42.3
Anticipated Duration (Months)
8.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
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

Study Type:
Interventional
Anticipated 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 :
Apr 15, 2021
Anticipated Primary Completion Date :
Jun 30, 2024
Anticipated Study Completion Date :
Oct 25, 2024

Arms and Interventions

ArmIntervention/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

    Primary Outcome Measures

    1. Effect on Overall Survival (OS) [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) [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 [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 [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 [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

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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):

    4. No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.

    5. Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.

    6. Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.

    7. Prior systemic therapies (Cohort 2 only):

    8. Documentation of PD-L1 positive status

    9. 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.

    10. 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.

    11. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.

    12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    13. 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.

    1. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.

    2. Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.

    3. QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.

    4. Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol

    5. Pregnant or lactating women

    6. Prior hematopoietic stem cell or bone marrow transplantation

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Alabama OncologyBirminghamAlabamaUnited States35235
    2Ironwood Cancer and Research CentersChandlerArizonaUnited States85224
    3Sansum ClinicSanta BarbaraCaliforniaUnited States93105
    4Florida Cancer Specialists - North (SCRI)Saint PetersburgFloridaUnited States33705
    5Moffitt Cancer CenterTampaFloridaUnited States33612
    6Illinois Cancer SpecialistsNilesIllinoisUnited States60005
    7Maryland Oncology Hematology, P.A.ClintonMarylandUnited States20735
    8Saint Luke's Cancer SpecialistsKansas CityMissouriUnited States64111
    9Comprehensive Cancer Genetics of NevadaLas VegasNevadaUnited States89128
    10Atrium Health Levine Cancer InstituteCharlotteNorth CarolinaUnited States28204
    11Northwest Cancer Specialists, PCPortlandOregonUnited States97225
    12UPC Pinnacle Health Cancer InstitutePittsburghPennsylvaniaUnited States15232
    13Abington Hematology OncologyWillow GrovePennsylvaniaUnited States19090
    14Tennessee Oncology ChattanoogaChattanoogaTennesseeUnited States37404
    15Tennessee Oncology (SCRI)NashvilleTennesseeUnited States37203
    16Texas Oncology- Austin CentralAustinTexasUnited States78731
    17Texas Oncology P.A.DallasTexasUnited States75231
    18Texas Oncology-Baylor Charles A. Sammons Cancer CenterDallasTexasUnited States75246
    19Texas Oncology-West TexasEl PasoTexasUnited States79912
    20Texas Oncology - Houston Memorial CityHoustonTexasUnited States77024
    21Texas Oncology P.A.HoustonTexasUnited States77070
    22Texas Oncology P.A.TylerTexasUnited States75702
    23Virginia Cancer Specialists, PCFairfaxVirginiaUnited States22031
    24Virginia Oncology AssociatesNorfolkVirginiaUnited States23502
    25Complex Oncology Center - BurgasBurgasBulgaria8000
    26Mhat Dr.Tota VenkovaGabrovoBulgaria5300
    27IMSP Institutul Oncologic, ARENSIA Exploratory MedicineChisinauMoldova, Republic ofMD-2025
    28MED-POLONIA Sp.z o.o.PoznanWielkopolskiePoland60-569
    29Instytut MSF Sp. z. o.o.ŁódźPoland90-302

    Sponsors and Collaborators

    • G1 Therapeutics, Inc.

    Investigators

    • Study Director: Clinical Contact, G1 Therapeutics, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    G1 Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT04799249
    Other Study ID Numbers:
    • G1T28-208
    • 2020-004930-39
    First Posted:
    Mar 16, 2021
    Last Update Posted:
    Oct 14, 2021
    Last Verified:
    Oct 1, 2021

    Study Results

    No Results Posted as of Oct 14, 2021