Clinical trial NCT04799249: Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: TNBC - Triple-Negative Breast Cancer
Breast Cancer
Keywords: 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
Lead sponsor: G1 Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-16
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Effect on Overall Survival (OS)
timeFrame: Cohort 1:From date of randomization up to 39 months
measure: Effect on Overall Survival (OS)
timeFrame: Cohort 2: From date of randomization up to 28 months
Secondary outcomes:
measure: Quality of life/Effects On Chemotherapy-Induced Fatigue
timeFrame: Cycle 1 Day 1 (each cycle is 21 days) up to 14 months
measure: Myeloprotective Effects
timeFrame: Cycle 1 Day 1 (each cycle is 21 days) up to 14 months
measure: Progression Free Survival
timeFrame: From date of randomization up to 14 months)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner M.D. Anderson Cancer Center
state: Arizona
city: Washington
country: United States
facility: Washington Cancer Institute at MedStar Washington Hospital Center - Oncology Research
state: District of Columbia
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North (SCRI)
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Clinton
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Kansas City
country: United States
facility: Saint Luke's Cancer Specialists
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Genetics of Nevada
state: Nevada
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Pittsburgh
country: United States
facility: UPC Pinnacle Health Cancer Institute
state: Pennsylvania
city: Chattanooga
country: United States
facility: Tennessee Oncology Chattanooga
state: Tennessee
city: Memphis
country: United States
facility: Baptist Cancer Cancer - Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology (SCRI)
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology- Austin Central
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology P.A.
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
state: Queensland
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre - Oncology
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Health
state: Victoria
city: North Sydney
country: Australia
facility: Mater Hospital Sydney
city: Burgas
country: Bulgaria
facility: Complex Oncology Center - Burgas
city: Sofia
country: Bulgaria
facility: Medical Ctr Nadezhda Clinical
city: Chaoyang
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Yuzhong
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Yuexiu
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangzhou
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Anhui Provincial Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Le Mans
country: France
facility: Centre Jean Bernard
state: Europe
city: Caen
country: France
facility: Centre Francois Baclesse
city: Montpellier
country: France
facility: ICM-Val d'Aurelle
city: Poitiers
country: France
facility: Centre Hospitalier de Poitiers
city: Toulouse
country: France
facility: Pharmacie Essais Cliniques
city: Villejuif
country: France
facility: Centre Leon Berard
city: Batumi
country: Georgia
facility: High Technology Hospital MedCenter LTD
state: Ajaria
city: Tbilisi
country: Georgia
facility: Acad.Fridon Todua Medical Center - Research Institute of Clinical Medicine
city: Tbilisi
country: Georgia
facility: ARENSIA Exploratory Medicine Harmony Health
city: Tbilisi
country: Georgia
facility: LTD Israeli-Georgian Medical Research Clinic Helsicore
city: Tbilisi
country: Georgia
facility: LTD Multiprofile Clinic Consilium Medulla
city: Tbilisi
country: Georgia
facility: TIM - Tbilisi Institute of Medicine LTD
city: Tbilisi
country: Georgia
facility: Institute Of Clinical Oncology LTD
city: Chisinau
country: Moldova, Republic of
facility: IMSP Institutul Oncologic, ARENSIA Exploratory Medicine
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Malopolskie
city: Poznan
country: Poland
facility: Med-Polonia Sp. Z o.o.
state: Wielkopolskie
city: Lodz
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi, Oddzial Chorob Rozrostowych
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej - Curie - Panstwowy Instytut Badawczy
city: Łódź
country: Poland
facility: Instytut MSF Sp. z. o.o.
city: Moscow
country: Russian Federation
facility: Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Oncology Dispensary"
state: Balashikha
city: Kazan
country: Russian Federation
facility: SAHI Republcx Clinical Oncology Dispensary of the Ministry of Healthcare of Tatarstan Republix
city: Moscow
country: Russian Federation
facility: FSBI Russian Scientific Center of Roentgenoradiology of the MoH of Russia
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution of Moscow Region "Moscow Reginoal Oncology Dispensary"
city: Omsk
country: Russian Federation
facility: Budgetary Healthcare Institution of Omsk Region "Clinical Oncological Dispensary"
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
state: Majadahonda
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajos
city: Barcelona
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Barcelona
country: Spain
facility: Vall d'Hebrón University Hospital
city: Barcelona
country: Spain
facility: Hospital Clìnic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Kapitanivka
country: Ukraine
facility: Yuri Prokopovich Spizhenko
state: Kyivska Oblast
city: Sumy
country: Ukraine
facility: Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady Sumskyi oblasnyi onkolohichnyi dyspanser
state: Sums'ka Oblast
city: Ternopil
country: Ukraine
facility: Komunalne nekomertsiine pidpryiemstvo Ternopilskyi oblasnyi klinichnyi onkolohichnyi dyspanser Ternopilskoi oblasnoi rady
state: Ternopil's'ka Oblast
city: Lutsk
country: Ukraine
facility: Volynskyi oblasnyi medychnyi tsentr onkolohii
state: Volyns'ka Oblast
city: Dnipro
country: Ukraine
facility: Komunalne nekomertsiine pidpryiemstvo Miska klinichna likarnia No 4 Dniprovskoi miskoi rady
Study officials:
affiliation: G1 Therapeutics, Inc.
name: Clinical Contact
role: STUDY_DIRECTOR
References:
citation: Goel S, Tan AR, Rugo HS, Aftimos P, Andric Z, Beelen A, Zhang J, Yi JS, Malik R, O'Shaughnessy J. Trilaciclib prior to gemcitabine plus carboplatin for metastatic triple-negative breast cancer: phase III PRESERVE 2. Future Oncol. 2022 Oct;18(33):3701-3711. doi: 10.2217/fon-2022-0773. Epub 2022 Sep 22.