Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab
- Conditions
- Myelosuppression AdultBladder CancerUrothelial CarcinomaChemotherapy-induced NeutropeniaMetastatic Bladder Cancer
- Interventions
- Registration Number
- NCT04887831
- Lead Sponsor
- G1 Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 92
- 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
-
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
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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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy Avelumab 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) Platinum-based chemotherapy followed by avelumab maintenance therapy Cisplatin Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg) Platinum-based chemotherapy followed by avelumab maintenance therapy Carboplatin Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg) Platinum-based chemotherapy followed by avelumab maintenance therapy Gemcitabine Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg) Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy Carboplatin 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) Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy Trilaciclib 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) Platinum-based chemotherapy followed by avelumab maintenance therapy Avelumab Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg) Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy Gemcitabine 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) Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy Cisplatin 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)
- Primary Outcome Measures
Name Time Method Progression-Free Survival 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) 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
Name Time Method Myeloprotective Effects Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy (up to 4 months) To assess the effects of trilaciclib on the neutrophil lineage as measured by the occurrence of severe neutropenia during platinum-based chemotherapy treatment
Anti-tumor Effects From date of randomization until date of death due to any cause (on average 25 months) 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.
Trial Locations
- Locations (34)
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Beacon Cancer Center PLLC
🇺🇸Coeur d'Alene, Idaho, United States
Institut Bergonié - Oncologie Médicale et Pédiatrique
🇫🇷Bordeaux cedex, Gironde, France
High Technology Hospital MedCenter LTD
🇬🇪Batumi, Ajaria, Georgia
Rocky Mountain Cancer Centers
🇺🇸Littleton, Colorado, United States
ALTHAIA, Xarxa Assistencial Universitiria de Manresa
🇪🇸Manresa, Barcelona, Spain
LTD "Multiprofile Clinic Consilium Medulla"
🇬🇪Tbilisi, Georgia
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint
🇭🇺Szolnok, Jász-Nagykun-Szolnok, Hungary
Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie
🇫🇷Strasbourg, Bas-Rhin, France
Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Országos Onkológiai Intézet
🇭🇺Budapest, Hungary
Valkyrie Clinical Trial
🇺🇸Los Angeles, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Florida Cancer Specialists - South
🇺🇸Fort Myers, Florida, United States
Woodlands Medical Specialists
🇺🇸Pensacola, Florida, United States
Florida Cancer Specialists - North
🇺🇸Saint Petersburg, Florida, United States
The Harry and Jeanette Weinberg Cancer Institute
🇺🇸Baltimore, Maryland, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Northwest Cancer Specialists, P.C.
🇺🇸Tigard, Oregon, United States
Centre Léon Bérard - Département d'oncologie médicale
🇫🇷Lyon, France
Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale
🇫🇷Paris, France
Institut de Cancérologie de Lorraine
🇫🇷Vandœuvre-lès-Nancy, France
National Center of Urology Named after Laur Managadze
🇬🇪Tbilisi, Georgia
Uzsoki Utcai Kórház
🇭🇺Budapest, Hungary
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital Universitario Vall d´Hebron
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona - Servicio de Oncología Médica
🇪🇸Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitario Lucus Augusti
🇪🇸Lugo, Spain
Fundación Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
H.U. V. de las Nieves
🇪🇸Granada, Spain
Hospital Politecnic Universitari La Fe
🇪🇸Valencia, Spain
Montefiore Medical Center
🇺🇸Bronx, New York, United States