Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab

Bladder Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04887831
• Other study ID #: G1T28-209
• Status: Terminated
• Phase: Phase 2
• Start date: June 4, 2021
• Est. completion date: March 1, 2024

Study information

• Verified date: March 2024
• Source: G1 Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 92
• Est. completion date: March 1, 2024
• Est. primary completion date: April 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years

2. Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV)

3. Measurable disease as defined by RECIST v1.1

4. No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents

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

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

7. Adequate organ function as demonstrated by normal laboratory values

Exclusion Criteria:

1. Prior treatment with IL-2, IFN-a, 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

2. 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)

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

4. QTcF interval > 480 msec. For patients with ventricular pacemakers, QTcF > 500 msec

5. Known hypersensitivity or allergy to avelumab, gemcitabine, cisplatin or carboplatin

6. Known severe hypersensitivity reactions to monoclonal antibodies (Grade =3), any history of anaphylaxis, or uncontrolled asthma

7. Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation

8. Pregnant or lactating women

9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent

10. Current use of immunosuppressive medication, EXCEPT for the following:

1. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)

2. Systemic corticosteroids at physiological doses =10 mg/day of prednisone or equivalent

3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma
• Carcinoma, Transitional Cell
• Chemotherapy-induced Neutropenia
• Metastatic Bladder Cancer
• Myelosuppression Adult
• Neutropenia
• Urinary Bladder Neoplasms
• Urothelial Carcinoma

Intervention

Drug:
• Trilaciclib
Trilaciclib administered IV prior to chemotherapy and avelumab maintenance therapy on each day chemotherapy and avelumab maintenance therapy is administered.
• Gemcitabine
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle
• Cisplatin
Cisplatin administered IV on Day 1 of each 21-day cycle
• Carboplatin
Carboplatin administered IV on Day 1 of each 21-day cycle
• Avelumab
Avelumab will be dosed on Day 1 of each 14-day maintenance cycle

Locations

Country	Name	City	State
France	Institut Bergonié - Oncologie Médicale et Pédiatrique	Bordeaux cedex	Gironde
France	Centre Léon Bérard - Département d'oncologie médicale	Lyon
France	Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale	Paris
France	Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie	Strasbourg	Bas-Rhin
France	Institut de Cancérologie de Lorraine	Vandœuvre-lès-Nancy
Georgia	High Technology Hospital MedCenter LTD	Batumi	Ajaria
Georgia	LTD "Multiprofile Clinic Consilium Medulla"	Tbilisi
Georgia	National Center of Urology Named after Laur Managadze	Tbilisi
Hungary	Országos Onkológiai Intézet	Budapest
Hungary	Uzsoki Utcai Kórház	Budapest
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint	Szolnok	Jász-Nagykun-Szolnok
Spain	Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona - Servicio de Oncología Médica	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d´Hebron	Barcelona
Spain	H.U. V. de las Nieves	Granada
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	ALTHAIA, Xarxa Assistencial Universitiria de Manresa	Manresa	Barcelona
Spain	Fundación Instituto Valenciano de Oncología	Valencia
Spain	Hospital Politecnic Universitari La Fe	Valencia
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	The Harry and Jeanette Weinberg Cancer Institute	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Beacon Cancer Center PLLC	Coeur d'Alene	Idaho
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	Rocky Mountain Cancer Centers	Littleton	Colorado
United States	Valkyrie Clinical Trial	Los Angeles	California
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Woodlands Medical Specialists	Pensacola	Florida
United States	Florida Cancer Specialists - North	Saint Petersburg	Florida
United States	Northwest Cancer Specialists, P.C.	Tigard	Oregon
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
G1 Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  France,  Georgia,  Hungary,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Anti-tumor Effects	To assess objective response rates as measured by RECIST 1.1	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	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.	From date of randomization until date of death due to any cause (on average 25 months)
Secondary	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	Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy (up to 4 months)