Back to resultsTrilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab (PRESERVE3)
Primary Purpose
Urothelial Carcinoma, Bladder Cancer, Myelosuppression Adult
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Trilaciclib
Gemcitabine
Cisplatin
Carboplatin
Avelumab
Sponsored by
About this trial
This is an interventional treatment trial for Urothelial Carcinoma focused on measuring Trilaciclib dihydrochloride/Cosela, Metastatic Urothelial Carcinoma, Cyclin-dependent kinase 4/6 inhibitor, Immuno-oncology, Solid tumor, Chemotherapy-induced myelosuppression, Myeloprotective
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years
- Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV)
- Measurable disease as defined by RECIST v1.1
- No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents
- 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 0-2
- Adequate organ function as demonstrated by normal laboratory values
Exclusion Criteria:
- Prior treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or CD137 agonists, or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody (including ipilimumab), or any other therapeutic antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways in any setting
- Malignancies other than urothelial carcinoma within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration)
- Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
- QTcF interval > 480 msec. For patients with ventricular pacemakers, QTcF > 500 msec
- Known hypersensitivity or allergy to avelumab, gemcitabine, cisplatin or carboplatin
- Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma
- Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation
- Pregnant or lactating women
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
Current use of immunosuppressive medication, EXCEPT for the following:
- Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
- Systemic corticosteroids at physiological doses ≤10 mg/day of prednisone or equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Sites / Locations
- Valkyrie Clinical Trial
- The Oncology Institute of Hope and Innovation
- Rocky Mountain Cancer Centers
- Florida Cancer Specialists - South
- Woodlands Medical Specialists
- Florida Cancer Specialists - North
- Beacon Cancer Center PLLC
- The Harry and Jeanette Weinberg Cancer Institute
- New York Oncology Hematology, P.C.
- Montefiore Medical Center
- University of North Carolina at Chapel Hill
- Northwest Cancer Specialists, P.C.
- Tennessee Oncology, PLLC
- Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie
- Institut Bergonié - Oncologie Médicale et Pédiatrique
- Centre Léon Bérard - Département d'oncologie médicale
- Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale
- Institut de Cancérologie de Lorraine
- High Technology Hospital MedCenter LTD
- National Center of Urology Named after Laur Managadze
- LTD "Multiprofile Clinic Consilium Medulla"
- Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint
- Országos Onkológiai Intézet
- Uzsoki Utcai Kórház
- Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
- ALTHAIA, Xarxa Assistencial Universitiria de Manresa
- Hospital Universitario Puerta de Hierro Majadahonda
- Hospital Universitario Vall d´Hebron
- Hospital Clinic de Barcelona - Servicio de Oncología Médica
- Hospital de la Santa Creu i Sant Pau
- H.U. V. de las Nieves
- Hospital Universitario Lucus Augusti
- Fundación Instituto Valenciano de Oncología
- Hospital Politecnic Universitari La Fe
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Platinum-based chemotherapy followed by avelumab maintenance therapy
Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy
Arm Description
Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg)
Trilaciclib (240 mg/m2) + Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Trilaciclib (240 mg/m2) + Avelumab (800 mg)
Outcomes
Primary Outcome Measures
Progression-Free Survival
To evaluate the effect of trilaciclib on progression-free survival (PFS) when administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy alone.
Secondary Outcome Measures
Anti-tumor Effects
To assess objective response rates as measured by RECIST 1.1
Anti-tumor Effects
To evaluate the effect of trilaciclib on overall survival (OS) when administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy alone.
Myeloprotective Effects
To assess the effects of trilaciclib on the neutrophil lineage as measured by the occurrence of severe neutropenia during platinum-based chemotherapy treatment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04887831
Brief Title
Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab
Acronym
PRESERVE3
Official Title
A Phase 2, Randomized, Open-Label Study of Trilaciclib Administered With First-Line Platinum-Based Chemotherapy and Avelumab Maintenance Therapy in Patients With Untreated, Locally Advanced or Metastatic Urothelial Carcinoma (PRESERVE 3)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 4, 2021 (Actual)
Primary Completion Date
June 1, 2023 (Actual)
Study Completion Date
May 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
G1 Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 2, multicenter, randomized, open-label study evaluating the safety and efficacy of trilaciclib administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy in patients receiving first-line treatment for advanced/metastatic bladder cancer.
Detailed Description
Patients will be randomly assigned (1:1) to receive standard of care platinum-based chemotherapy (with or without the addition of trilaciclib) administered intravenously (IV) in 21-day cycles followed by standard of care avelumab maintenance therapy (with or without the addition of trilaciclib) administered IV in 14-day cycles.
Patients enrolled in the study will be eligible to receive 4-6 cycles of platinum-based chemotherapy, and patients without progressive disease (PD) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (i.e., with an ongoing complete response [CR], partial response [PR], or stable disease) after platinum-based chemotherapy will be eligible to receive avelumab maintenance therapy until disease progression, unacceptable toxicity, withdrawal of consent, Investigator decision, or the end of the trial, whichever comes first.
Patients will be followed for survival approximately every 3 months after receiving the last dose of study medication.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma, Bladder Cancer, Myelosuppression Adult, Chemotherapy-induced Neutropenia, Metastatic Bladder Cancer
Keywords
Trilaciclib dihydrochloride/Cosela, Metastatic Urothelial Carcinoma, Cyclin-dependent kinase 4/6 inhibitor, Immuno-oncology, Solid tumor, Chemotherapy-induced myelosuppression, Myeloprotective
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Random assignment (1:1) to one of two treatment arms
Masking
None (Open Label)
Allocation
Randomized
Enrollment
92 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Platinum-based chemotherapy followed by avelumab maintenance therapy
Arm Type
Active Comparator
Arm Description
Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg)
Arm Title
Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy
Arm Type
Experimental
Arm Description
Trilaciclib (240 mg/m2) + Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Trilaciclib (240 mg/m2) + Avelumab (800 mg)
Intervention Type
Drug
Intervention Name(s)
Trilaciclib
Other Intervention Name(s)
Cosela, G1T28
Intervention Description
Trilaciclib administered IV prior to chemotherapy and avelumab maintenance therapy on each day chemotherapy and avelumab maintenance therapy is administered.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin administered IV on Day 1 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin administered IV on Day 1 of each 21-day cycle
Intervention Type
Drug
Intervention Name(s)
Avelumab
Other Intervention Name(s)
Bavencio
Intervention Description
Avelumab will be dosed on Day 1 of each 14-day maintenance cycle
Primary Outcome Measure Information:
Title
Progression-Free Survival
Description
To evaluate the effect of trilaciclib on progression-free survival (PFS) when administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy alone.
Time Frame
From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first (on average 7 months)
Secondary Outcome Measure Information:
Title
Anti-tumor Effects
Description
To assess objective response rates as measured by RECIST 1.1
Time Frame
From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first (on average 7 months)
Title
Anti-tumor Effects
Description
To evaluate the effect of trilaciclib on overall survival (OS) when administered with platinum-based chemotherapy followed by trilaciclib administered with avelumab maintenance therapy compared with platinum-based chemotherapy followed by avelumab maintenance therapy alone.
Time Frame
From date of randomization until date of death due to any cause (on average 25 months)
Title
Myeloprotective Effects
Description
To assess the effects of trilaciclib on the neutrophil lineage as measured by the occurrence of severe neutropenia during platinum-based chemotherapy treatment
Time Frame
Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy (up to 4 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years
Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV)
Measurable disease as defined by RECIST v1.1
No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents
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 0-2
Adequate organ function as demonstrated by normal laboratory values
Exclusion Criteria:
Prior treatment with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or CD137 agonists, or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody (including ipilimumab), or any other therapeutic antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways in any setting
Malignancies other than urothelial carcinoma within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration)
Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
QTcF interval > 480 msec. For patients with ventricular pacemakers, QTcF > 500 msec
Known hypersensitivity or allergy to avelumab, gemcitabine, cisplatin or carboplatin
Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma
Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation
Pregnant or lactating women
Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
Current use of immunosuppressive medication, EXCEPT for the following:
Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
Systemic corticosteroids at physiological doses ≤10 mg/day of prednisone or equivalent
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Contact
Organizational Affiliation
G1 Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Valkyrie Clinical Trial
City
Los Angeles
State/Province
California
ZIP/Postal Code
90067
Country
United States
Facility Name
The Oncology Institute of Hope and Innovation
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Littleton
State/Province
Colorado
ZIP/Postal Code
80120
Country
United States
Facility Name
Florida Cancer Specialists - South
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
Woodlands Medical Specialists
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32503
Country
United States
Facility Name
Florida Cancer Specialists - North
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33705
Country
United States
Facility Name
Beacon Cancer Center PLLC
City
Coeur d'Alene
State/Province
Idaho
ZIP/Postal Code
83814
Country
United States
Facility Name
The Harry and Jeanette Weinberg Cancer Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21237
Country
United States
Facility Name
New York Oncology Hematology, P.C.
City
Albany
State/Province
New York
ZIP/Postal Code
12206
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Northwest Cancer Specialists, P.C.
City
Tigard
State/Province
Oregon
ZIP/Postal Code
46241
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie
City
Strasbourg
State/Province
Bas-Rhin
ZIP/Postal Code
67091
Country
France
Facility Name
Institut Bergonié - Oncologie Médicale et Pédiatrique
City
Bordeaux cedex
State/Province
Gironde
ZIP/Postal Code
33076
Country
France
Facility Name
Centre Léon Bérard - Département d'oncologie médicale
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Institut de Cancérologie de Lorraine
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54519
Country
France
Facility Name
High Technology Hospital MedCenter LTD
City
Batumi
State/Province
Ajaria
ZIP/Postal Code
6010
Country
Georgia
Facility Name
National Center of Urology Named after Laur Managadze
City
Tbilisi
ZIP/Postal Code
0144
Country
Georgia
Facility Name
LTD "Multiprofile Clinic Consilium Medulla"
City
Tbilisi
ZIP/Postal Code
186
Country
Georgia
Facility Name
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint
City
Szolnok
State/Province
Jász-Nagykun-Szolnok
ZIP/Postal Code
H-5000
Country
Hungary
Facility Name
Országos Onkológiai Intézet
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Uzsoki Utcai Kórház
City
Budapest
ZIP/Postal Code
H-1145
Country
Hungary
Facility Name
Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
ALTHAIA, Xarxa Assistencial Universitiria de Manresa
City
Manresa
State/Province
Barcelona
ZIP/Postal Code
08243
Country
Spain
Facility Name
Hospital Universitario Puerta de Hierro Majadahonda
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Universitario Vall d´Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic de Barcelona - Servicio de Oncología Médica
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
H.U. V. de las Nieves
City
Granada
ZIP/Postal Code
18014
Country
Spain
Facility Name
Hospital Universitario Lucus Augusti
City
Lugo
ZIP/Postal Code
27003
Country
Spain
Facility Name
Fundación Instituto Valenciano de Oncología
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Hospital Politecnic Universitari La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab
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