Clinical trial NCT04887831: Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: G1 Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-14
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Random assignment (1:1) to one of two treatment arms
Primary purpose: TREATMENT

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.

Eligibility criteria: 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-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
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)

Primary outcomes:
measure: Progression-Free Survival
timeFrame: 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 outcomes:
measure: Anti-tumor Effects
timeFrame: 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)
measure: Anti-tumor Effects
timeFrame: From date of randomization until date of death due to any cause (on average 25 months)
measure: Myeloprotective Effects
timeFrame: Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy (up to 4 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trial
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South
state: Florida
city: Pensacola
country: United States
facility: Woodlands Medical Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North
state: Florida
city: Coeur d'Alene
country: United States
facility: Beacon Cancer Center PLLC
state: Idaho
city: Baltimore
country: United States
facility: The Harry and Jeanette Weinberg Cancer Institute
state: Maryland
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Tigard
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie
state: Bas-Rhin
city: Bordeaux cedex
country: France
facility: Institut Bergonié - Oncologie Médicale et Pédiatrique
state: Gironde
city: Lyon
country: France
facility: Centre Léon Bérard - Département d'oncologie médicale
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Batumi
country: Georgia
facility: High Technology Hospital MedCenter LTD
state: Ajaria
city: Tbilisi
country: Georgia
facility: National Center of Urology Named after Laur Managadze
city: Tbilisi
country: Georgia
facility: LTD "Multiprofile Clinic Consilium Medulla"
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint
state: Jász-Nagykun-Szolnok
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet
city: Budapest
country: Hungary
facility: Uzsoki Utcai Kórház
city: Badalona
country: Spain
facility: Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Manresa
country: Spain
facility: ALTHAIA, Xarxa Assistencial Universitiria de Manresa
state: Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d´Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona - Servicio de Oncología Médica
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Granada
country: Spain
facility: H.U. V. de las Nieves
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Politecnic Universitari La Fe
Study officials:
affiliation: G1 Therapeutics, Inc.
name: Clinical Contact
role: STUDY_DIRECTOR
References: