Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab (PRESERVE3)
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| ClinicalTrials.gov Identifier: NCT04887831 |
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Recruitment Status :
Active, not recruiting
First Posted : May 14, 2021
Last Update Posted : January 26, 2023
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Sponsor:
G1 Therapeutics, Inc.
Information provided by (Responsible Party):
G1 Therapeutics, Inc.
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Urothelial Carcinoma Bladder Cancer Myelosuppression Adult Chemotherapy-induced Neutropenia Metastatic Bladder Cancer | Drug: Trilaciclib Drug: Gemcitabine Drug: Cisplatin Drug: Carboplatin Drug: Avelumab | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 92 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Random assignment (1:1) to one of two treatment arms |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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) |
| Actual Study Start Date : | June 4, 2021 |
| Estimated Primary Completion Date : | March 2023 |
| Estimated Study Completion Date : | May 2024 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Platinum-based chemotherapy followed by avelumab maintenance therapy
Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) or Carboplatin (AUC 4.5) followed by Avelumab (800 mg)
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Drug: Gemcitabine
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle Drug: Cisplatin Cisplatin administered IV on Day 1 of each 21-day cycle Drug: Carboplatin Carboplatin administered IV on Day 1 of each 21-day cycle Drug: Avelumab Avelumab will be dosed on Day 1 of each 14-day maintenance cycle
Other Name: Bavencio |
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Experimental: Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy
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)
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Drug: Trilaciclib
Trilaciclib administered IV prior to chemotherapy and avelumab maintenance therapy on each day chemotherapy and avelumab maintenance therapy is administered.
Other Names:
Drug: Gemcitabine Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle Drug: Cisplatin Cisplatin administered IV on Day 1 of each 21-day cycle Drug: Carboplatin Carboplatin administered IV on Day 1 of each 21-day cycle Drug: Avelumab Avelumab will be dosed on Day 1 of each 14-day maintenance cycle
Other Name: Bavencio |
Primary Outcome Measures :
- Progression-Free Survival [ 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) ]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 [ 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) ]To assess objective response rates as measured by RECIST 1.1
- Anti-tumor Effects [ Time Frame: 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.
- Myeloprotective Effects [ Time Frame: 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
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04887831
Locations
Show 34 study locations
Sponsors and Collaborators
G1 Therapeutics, Inc.
Investigators
| Study Director: | Clinical Contact | G1 Therapeutics, Inc. |
| Responsible Party: | G1 Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT04887831 |
| Other Study ID Numbers: |
G1T28-209 |
| First Posted: | May 14, 2021 Key Record Dates |
| Last Update Posted: | January 26, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by G1 Therapeutics, Inc.:
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Trilaciclib dihydrochloride/Cosela Metastatic Urothelial Carcinoma Cyclin-dependent kinase 4/6 inhibitor Immuno-oncology |
Solid tumor Chemotherapy-induced myelosuppression Myeloprotective |
Additional relevant MeSH terms:
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Carcinoma Urinary Bladder Neoplasms Carcinoma, Transitional Cell Neutropenia Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Urinary Bladder Diseases |
Urologic Diseases Male Urogenital Diseases Agranulocytosis Leukopenia Leukocyte Disorders Hematologic Diseases Carboplatin Gemcitabine Avelumab Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological |