Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC)
- Conditions
- TNBC - Triple-Negative Breast CancerBreast Cancer
- Interventions
- Registration Number
- NCT04799249
- Lead Sponsor
- G1 Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 194
-
Age >/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.
-
Documentation of triple negative breast cancer (estrogen and progesterone receptor <1% and HER2-negative)
-
Prior systemic therapies (Cohort 1 only):
- No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
- Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
- Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.
-
Prior systemic therapies (Cohort 2 only):
- Documentation of PD-L1 positive status
- 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.
-
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.
-
Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
-
Adequate organ function as demonstrated by normal laboratory values
-
Prior treatment with gemcitabine in any setting.
-
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.
-
Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
-
Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.
-
QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.
-
Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol
-
Pregnant or lactating women
-
Prior hematopoietic stem cell or bone marrow transplantation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + gemcitabine + carboplatin Placebo The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib. Trilaciclib + gemcitabine + carboplatin Gemcitabine Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2) Trilaciclib + gemcitabine + carboplatin Trilaciclib Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2) Trilaciclib + gemcitabine + carboplatin Carboplatin Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2) Placebo + gemcitabine + carboplatin Carboplatin The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib. Placebo + gemcitabine + carboplatin Gemcitabine The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
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.
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
Trial Locations
- Locations (71)
Banner M.D. Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Florida Cancer Specialists - North (SCRI)
🇺🇸Saint Petersburg, Florida, United States
Maryland Oncology Hematology, P.A.
🇺🇸Clinton, Maryland, United States
Comprehensive Cancer Genetics of Nevada
🇺🇸Las Vegas, Nevada, United States
UPC Pinnacle Health Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Oncology P.A.
🇺🇸Tyler, Texas, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Sunshine Coast University Hospital
🇦🇺Birtinya, Queensland, Australia
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Peter MacCallum Cancer Centre - Oncology
🇦🇺East Melbourne, Victoria, Australia
Cabrini Health
🇦🇺Malvern, Victoria, Australia
Mater Hospital Sydney
🇦🇺North Sydney, Australia
Complex Oncology Center - Burgas
🇧🇬Burgas, Bulgaria
Medical Ctr Nadezhda Clinical
🇧🇬Sofia, Bulgaria
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Chaoyang, Beijing, China
Sun Yat-sen University Cancer Center
🇨🇳Yuexiu, Guangzhou, China
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Yuzhong, Chongqing, China
The Fourth Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
ICM-Val d'Aurelle
🇫🇷Montpellier, France
Tianjin Cancer Hospital
🇨🇳Tianjin, Tianjin, China
Centre Jean Bernard
🇫🇷Le Mans, Europe, France
Centre Francois Baclesse
🇫🇷Caen, France
Pharmacie Essais Cliniques
🇫🇷Toulouse, France
Centre Hospitalier de Poitiers
🇫🇷Poitiers, France
Centre Leon Berard
🇫🇷Villejuif, France
High Technology Hospital MedCenter LTD
🇬🇪Batumi, Ajaria, Georgia
Acad.Fridon Todua Medical Center - Research Institute of Clinical Medicine
🇬🇪Tbilisi, Georgia
ARENSIA Exploratory Medicine Harmony Health
🇬🇪Tbilisi, Georgia
TIM - Tbilisi Institute of Medicine LTD
🇬🇪Tbilisi, Georgia
IMSP Institutul Oncologic, ARENSIA Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
Med-Polonia Sp. Z o.o.
🇵🇱Poznan, Wielkopolskie, Poland
Centrum Medyczne Pratia Poznan
🇵🇱Skorzewo, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi, Oddzial Chorob Rozrostowych
🇵🇱Lodz, Poland
Instytut MSF Sp. z. o.o.
🇵🇱Łódź, Poland
SAHI Republcx Clinical Oncology Dispensary of the Ministry of Healthcare of Tatarstan Republix
🇷🇺Kazan, Russian Federation
FSBI Russian Scientific Center of Roentgenoradiology of the MoH of Russia
🇷🇺Moscow, Russian Federation
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Budgetary Healthcare Institution of Omsk Region "Clinical Oncological Dispensary"
🇷🇺Omsk, Russian Federation
State Budgetary Healthcare Institution of Moscow Region "Moscow Reginoal Oncology Dispensary"
🇷🇺Moscow, Russian Federation
Hospital Puerta de Hierro Majadahonda
🇪🇸Madrid, Majadahonda, Spain
Hospital Universitario de Badajos
🇪🇸Badajoz, Spain
Hospital Clìnic de Barcelona
🇪🇸Barcelona, Spain
Vall d'Hebrón University Hospital
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Barcelona, Spain
Volynskyi oblasnyi medychnyi tsentr onkolohii
🇺🇦Lutsk, Volyns'ka Oblast, Ukraine
Komunalne nekomertsiine pidpryiemstvo Miska klinichna likarnia No 4 Dniprovskoi miskoi rady
🇺🇦Dnipro, Ukraine
Anhui Provincial Hospital
🇨🇳Harbin, Heilongjiang, China
First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Tennessee Oncology (SCRI)
🇺🇸Nashville, Tennessee, United States
Narodowy Instytut Onkologii im. Marii Sklodowskiej - Curie - Panstwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Yuri Prokopovich Spizhenko
🇺🇦Kapitanivka, Kyivska Oblast, Ukraine
Komunalne nekomertsiine pidpryiemstvo Ternopilskyi oblasnyi klinichnyi onkolohichnyi dyspanser Ternopilskoi oblasnoi rady
🇺🇦Ternopil, Ternopil's'ka Oblast, Ukraine
Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
LTD Israeli-Georgian Medical Research Clinic Helsicore
🇬🇪Tbilisi, Georgia
Institute Of Clinical Oncology LTD
🇬🇪Tbilisi, Georgia
Washington Cancer Institute at MedStar Washington Hospital Center - Oncology Research
🇺🇸Washington, District of Columbia, United States
Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady Sumskyi oblasnyi onkolohichnyi dyspanser
🇺🇦Sumy, Sums'ka Oblast, Ukraine
Baptist Cancer Cancer - Oncology
🇺🇸Memphis, Tennessee, United States
LTD Multiprofile Clinic Consilium Medulla
🇬🇪Tbilisi, Georgia
Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Oncology Dispensary"
🇷🇺Moscow, Balashikha, Russian Federation
Pratia MCM Krakow
🇵🇱Krakow, Malopolskie, Poland
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Saint Luke's Cancer Specialists
🇺🇸Kansas City, Missouri, United States
Texas Oncology- Austin Central
🇺🇸Austin, Texas, United States