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.
Brief Title
Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Urothelial Carcinoma
Bladder Cancer
Myelosuppression Adult
Chemotherapy-induced Neutropenia
Metastatic Bladder Cancer
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)
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)
Inclusion 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
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
Gender
All
Gender Based
false
Keywords
Trilaciclib dihydrochloride/Cosela
Metastatic Urothelial Carcinoma
Cyclin-dependent kinase 4/6 inhibitor
Immuno-oncology
Solid tumor
Chemotherapy-induced myelosuppression
Myeloprotective
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04887831
Org Class
Industry
Org Full Name
G1 Therapeutics, Inc.
Org Study Id
G1T28-209
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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.
Outcome Measure
Progression-Free Survival
Outcome 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 Outcomes
Outcome Description
To assess objective response rates as measured by RECIST 1.1
Outcome 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)
Outcome Measure
Anti-tumor Effects
Outcome 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.
Outcome Time Frame
From date of randomization until date of death due to any cause (on average 25 months)
Outcome Measure
Anti-tumor Effects
Outcome Description
To assess the effects of trilaciclib on the neutrophil lineage as measured by the occurrence of severe neutropenia during platinum-based chemotherapy treatment
Outcome Time Frame
Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy (up to 4 months)
Outcome Measure
Myeloprotective Effects
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404