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

Breast Cancer Clinical Trial

— PRESERVE 2  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04799249
• Other study ID #: G1T28-208
• Secondary ID: 2020-004930-39
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 15, 2021
• Est. completion date: October 25, 2024

Study information

• Verified date: May 2023
• Source: G1 Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 194
• Est. completion date: October 25, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Trilaciclib
Trilaciclib administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.
• Placebo
Placebo administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.
• Gemcitabine
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle.
• Carboplatin
Carboplatin administered IV on Day 1 and Day 8 of each 21-day cycle.

Locations

Country	Name	City	State
Australia	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
Bulgaria	Complex Oncology Center - Burgas	Burgas
Bulgaria	Medical Ctr Nadezhda Clinical	Sofia
China	Jilin Cancer Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	Cancer Hospital Chinese Academy of Medical Sciences	Chaoyang	Beijing
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Harbin	Heilongjiang
China	Fudan University Shanghai Cancer Center	Shanghai
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	Sun Yat-sen University Cancer Center	Yuexiu	Guangzhou
China	The First Affiliated Hospital of Chongqing Medical University	Yuzhong	Chongqing
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
France	Centre Francois Baclesse	Caen
France	Centre Jean Bernard	Le Mans	Europe
France	ICM-Val d'Aurelle	Montpellier
France	Centre Hospitalier de Poitiers	Poitiers
France	Pharmacie Essais Cliniques	Toulouse
France	Centre Leon Berard	Villejuif
Georgia	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	Institute Of Clinical Oncology LTD	Tbilisi
Georgia	LTD Israeli-Georgian Medical Research Clinic Helsicore	Tbilisi
Georgia	LTD Multiprofile Clinic Consilium Medulla	Tbilisi
Georgia	TIM - Tbilisi Institute of Medicine LTD	Tbilisi
Moldova, Republic of	IMSP Institutul Oncologic, ARENSIA Exploratory Medicine	Chisinau
Poland	Pratia MCM Krakow	Krakow	Malopolskie
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi, Oddzial Chorob Rozrostowych	Lodz
Poland	Instytut MSF Sp. z. o.o.	Lódz
Poland	Med-Polonia Sp. Z o.o.	Poznan	Wielkopolskie
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej - Curie - Panstwowy Instytut Badawczy	Warszawa
Russian Federation	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	Saint-Petersburg State Budgetary Healthcare Institution "City Clinical Oncology Dispensary"	Moscow	Balashikha
Russian Federation	State Budgetary Healthcare Institution of Moscow Region "Moscow Reginoal Oncology Dispensary"	Moscow
Russian Federation	Budgetary Healthcare Institution of Omsk Region "Clinical Oncological Dispensary"	Omsk
Spain	Hospital Universitario de Badajos	Badajoz
Spain	Hospital Clìnic de Barcelona	Barcelona
Spain	Hospital Universitario 12 de Octubre	Barcelona
Spain	Vall d'Hebrón University Hospital	Barcelona
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Puerta de Hierro Majadahonda	Madrid	Majadahonda
Spain	Hospital Universitario Ramón y Cajal	Madrid
Ukraine	Komunalne nekomertsiine pidpryiemstvo Miska klinichna likarnia No 4 Dniprovskoi miskoi rady	Dnipro
Ukraine	Yuri Prokopovich Spizhenko	Kapitanivka	Kyivska Oblast
Ukraine	Volynskyi oblasnyi medychnyi tsentr onkolohii	Lutsk	Volyns'ka Oblast
Ukraine	Komunalne nekomertsiine pidpryiemstvo Sumskoi oblasnoi rady Sumskyi oblasnyi onkolohichnyi dyspanser	Sumy	Sums'ka Oblast
Ukraine	Komunalne nekomertsiine pidpryiemstvo Ternopilskyi oblasnyi klinichnyi onkolohichnyi dyspanser Ternopilskoi oblasnoi rady	Ternopil	Ternopil's'ka Oblast
United States	Texas Oncology- Austin Central	Austin	Texas
United States	Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	Maryland Oncology Hematology, P.A.	Clinton	Maryland
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Duke Cancer Center	Durham	North Carolina
United States	Banner M.D. Anderson Cancer Center	Gilbert	Arizona
United States	Saint Luke's Cancer Specialists	Kansas City	Missouri
United States	Comprehensive Cancer Genetics of Nevada	Las Vegas	Nevada
United States	Baptist Cancer Cancer - Oncology	Memphis	Tennessee
United States	Tennessee Oncology (SCRI)	Nashville	Tennessee
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	UPC Pinnacle Health Cancer Institute	Pittsburgh	Pennsylvania
United States	Florida Cancer Specialists - North (SCRI)	Saint Petersburg	Florida
United States	Moffitt Cancer Center	Tampa	Florida
United States	Texas Oncology P.A.	Tyler	Texas
United States	Washington Cancer Institute at MedStar Washington Hospital Center - Oncology Research	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
G1 Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  China,  France,  Georgia,  Moldova, Republic of,  Poland,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect on Overall Survival (OS)	(Cohort 1):To evaluate the effect of trilaciclib on overall survival (OS) compared with placebo in patients receiving first-line gemcitabine and carboplatin.	Cohort 1:From date of randomization up to 39 months
Primary	Effect on Overall Survival (OS)	(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	Cohort 2: From date of randomization up to 28 months
Secondary	Quality of life/Effects On Chemotherapy-Induced Fatigue	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	Cycle 1 Day 1 (each cycle is 21 days) up to 14 months
Secondary	Myeloprotective Effects	Occurrence of cytopenias, febrile neutropenia, hospitalization due to chemotherapy-induced myelosuppression, RBC and platelet transfusions, growth factor administration, and dose reductions and delays	Cycle 1 Day 1 (each cycle is 21 days) up to 14 months
Secondary	Progression Free Survival	To evaluate the effect of trilaciclib on progression-free survival (PFS) compared with placebo in patients receiving gemcitabine and carboplatin.	From date of randomization up to 14 months)