Urothelial CarcinomaPhase 2PRESERVE3NCT04887831
Trilaciclib, a CDK 4/6 Inhibitor, in Patients With Advanced/Metastatic Bladder Cancer Receiving Chemotherapy Then Avelumab
A Phase 2 study testing Trilaciclib, Gemcitabine and Cisplatin in people with Urothelial Carcinoma and Bladder Cancer, run by G1 Therapeutics, Inc. at 34 sites in 5 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma, Bladder Cancer, Myelosuppression Adult
- What is being tested?
- Trilaciclib, Gemcitabine and Cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 34 sitesin 5 countries
- Study dates
- 4 Jun 2021to 1 Mar 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV) (also termed Transitional cell carcinoma [TCC] or Urothelial cell carcinoma [UCC] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
- Participants with mixed histologies are required to have a dominant transitional cell pattern (small cell carcinoma of any proportion is not allowed)
- Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical Stage T4b) or bulky nodal metastasis (N2-N3)
- Measurable disease as defined by RECIST v1.1
- Previously irradiated lesions should not be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions.
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- Considered to be eligible to receive platinum-based chemotherapy and avelumab maintenance therapy, in the Investigator's judgment
- No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents
- For participants who received prior adjuvant/neoadjuvant chemotherapy for urothelial carcinoma, a treatment-free interval > 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment-naïve in the metastatic setting. If a participant received adjuvant/neoadjuvant chemoradiation for urothelial carcinoma, a treatment-free interval >12 months between last platinum dose and the date of recurrence is required.
- For participants who received prior Immune checkpoint inhibitors (ICI) therapy in the adjuvant/neoadjuvant setting, a treatment-free interval > 3 months between the last dose of ICI and date of recurrence is required.
- Prior local intravesical chemotherapy or immunotherapy is allowed if completed ≥4 weeks prior to the initiation of study treatment
- A formalin-fixed paraffin-embedded (FFPE) tumor tissue block (75-micron) or at least 15 (5-micron) unstained slides from archival or fresh tumor biopsy or resection; the most recent biopsy tissue preferred. Participants who have fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with the Medical Monitor.
- Tumor tissue should be of good quality based on total and viable tumor content. For core-needle biopsy specimens, at least three cores should be submitted for evaluation.
- Transurethral resection of bladder tumor (TURBT) specimens must contain a muscle -invasive component (i.e., T2 or greater) of the bladder tumor as verified by local pathology review. If the TURBT specimens do not contain a muscle-invasive component, then specimens obtained at the time of cystectomy/nephroureterectomy (i.e., pT2 or greater) or metastatic spread (i.e., a sample from a metastatic lesion) will be required prior to randomization. An archival specimen, if available, should also be submitted.
- Participants who do not have tissue specimens that meet eligibility requirements may undergo a biopsy during the screening period. Acceptable samples include core needle biopsies for deep tumor tissue (minimum three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions.
- Tumor tissue from bone metastases is not evaluable for programmed death-ligand 1 (PD-L1) expression and is therefore not acceptable.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate organ function as demonstrated by the following laboratory values:
- Hemoglobin ≥9.0 gram per deciliter (g/dL) in the absence of RBC transfusion or ESA administration within 14 days prior to first dose of study drug
- Absolute neutrophil count (ANC) ≥1.5 × 10^9/L
- Platelet count ≥100 × 10^9/L
- Estimated glomerular filtration rate ≥ 30 mL/minute/1.73 m^2
- Total bilirubin ≤1.5 × upper limit of normal (ULN) (<3 ULN if Gilbert's disease)
- ALT and AST ≤2.5 × ULN in the absence of liver metastasis or <5 × ULN in the presence of liver metastasis
- Resolution of nonhematologic toxicities from prior systemic therapy, radiation therapy, or surgical procedures to ≤ Grade 1
- Alopecia and sensory neuropathy ≤ Grade 2, as well as any electrolyte laboratory abnormalities not constituting a safety risk based on investigator's judgment are acceptable
- Predicted life expectancy of ≥3 months
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol
Who cannot join
- Prior treatment with IL-2, IFN-α, 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 within 12 months prior to randomization
- Malignancies other than urothelial carcinoma within 2 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration), or other non-clinically significant cancers, which may be considered after discussion with the medical monitor
- Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids. Participant must be off steroids administered for brain metastases for at least 2 weeks prior to the first dose of study drugs. No stereotactic radiation within 1 week or whole-brain radiation within 14 days prior to first dose of study drugs
- Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure (≥ Class II New York Heart Association functional classification system), myocardial infarction within 6 months prior to first dose of study drugs, unstable angina, or serious cardiac arrhythmia requiring medication
- QTcF interval > 480 msec. For participants with ventricular pacemakers, QTcF > 500 msec
- Known history of stroke or cerebrovascular accident within 6 months prior to first dose of study drugs
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- Known history of serious, chronic active infection (e.g., human immunodeficiency virus, hepatitis B or C, tuberculosis, etc.)
- Viral load indicative of HIV, HIV 1/2 antibodies, positive hepatitis B virus surface antigen or hepatitis C virus ribonucleic acid (RNA) if anti-hepatitis C virus antibody screening test positive
- Severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
- Therapeutic oral or IV antibiotic use within 2 weeks prior to randomization
- Participants receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease or for dental extraction) are eligible
- Other uncontrolled serious chronic disease or psychiatric condition that in the Investigator's opinion could affect participant safety, compliance, or follow-up in the protocol
- Receipt of any investigational medication within 4 weeks, or at least 5 half-lives, whichever is greater, prior to the first dose of study drugs
- Known hypersensitivity or allergy to study drugs or any component in their formulations
- Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of asthma symptom control per Global Initiative for Asthma [GINA] 2020)
- Prior hematopoietic stem cell or bone marrow transplantation, or solid organ transplantation
- Radiotherapy to any non-Central nervous system (CNS) site within 1 week prior to the first dose of study drugs, or within 2 weeks to any CNS sites
- Pregnant or lactating women
- Women of childbearing potential must have negative serum pregnancy test result within 7 days prior to initiating study treatment
- Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study
- Received a live, attenuated vaccine within 4 weeks prior to the first dose of study drugs
- Inactive vaccines, including but not limited to influenza vaccine, pneumococcal vaccine, shingles vaccine, and regionally approved Covid-19 vaccines are allowed
- Participants must agree not to receive a live, attenuated influenza vaccine during study treatment
- History of immune colitis, inflammatory bowel disease, idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Participants with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
- 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)
- Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or participants who are employees of G1 Therapeutics, Inc. directly involved in the conduct of the study.
Trial locations and contacts
34 sites in 5 countries.
34 sites in 5 countries
United States13 sites
New York Oncology Hematology, P.C.
Albany, New York, 12206
The Harry and Jeanette Weinberg Cancer Institute
Baltimore, Maryland, 21237
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Beacon Cancer Center PLLC
Coeur d'Alene, Idaho, 83814
Florida Cancer Specialists - South
Fort Myers, Florida, 33901
Rocky Mountain Cancer Centers
Littleton, Colorado, 80120
Valkyrie Clinical Trial
Los Angeles, California, 90067
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Woodlands Medical Specialists
Pensacola, Florida, 32503
Florida Cancer Specialists - North
St. Petersburg, Florida, 33705
Montefiore Medical Center
The Bronx, New York, 10461
Northwest Cancer Specialists, P.C.
Tigard, Oregon, 46241
The Oncology Institute of Hope and Innovation
Whittier, California, 90603
Spain10 sites
Institut Català d'Oncologia-Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Universitario Vall d´Hebron
Barcelona, 08035
Hospital Clinic de Barcelona - Servicio de Oncología Médica
Barcelona, 08036
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
H.U. V. de las Nieves
Granada, 18014
Hospital Universitario Lucus Augusti
Lugo, 27003
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
ALTHAIA, Xarxa Assistencial Universitiria de Manresa
Manresa, Barcelona, 08243
Fundación Instituto Valenciano de Oncología
Valencia, 46009
Hospital Politecnic Universitari La Fe
Valencia, 46026
France5 sites
Institut Bergonié - Oncologie Médicale et Pédiatrique
Bordeaux, Gironde, 33076
Centre Léon Bérard - Département d'oncologie médicale
Lyon, 69373
Hôpital Européen Georges Pompidou - Service d'Oncologie Médicale
Paris, 75015
Hopitaux Universitaires de Strasbourg - Service Oncologie et Hématologie
Strasbourg, Bas-Rhin, 67091
Institut de Cancérologie de Lorraine
Vandœuvre-lès-Nancy, 54519
Georgia3 sites
High Technology Hospital MedCenter LTD
Batumi, Adjara, 6010
National Center of Urology Named after Laur Managadze
Tbilisi, 0144
LTD "Multiprofile Clinic Consilium Medulla"
Tbilisi, 186
Hungary3 sites
Országos Onkológiai Intézet
Budapest, 1122
Uzsoki Utcai Kórház
Budapest, H-1145
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendeloint
Szolnok, Jász-Nagykun-Szolnok, H-5000
About this study
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)
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 participants receiving first-line treatment for advanced/metastatic urothelial carcinoma.
Read the detailed description
Participants 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.
Participants enrolled in the study will be eligible to receive 4-6 cycles of platinum-based chemotherapy, and participants 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 [SD]) 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.
Participants will be followed for survival approximately every 3 months after receiving the last dose of study medication.
- Conditions
- Urothelial Carcinoma, Bladder Cancer, Myelosuppression Adult, Chemotherapy-induced Neutropenia, Metastatic Bladder Cancer
- Being tested
- Trilaciclib, Gemcitabine, Cisplatin, Carboplatin, Avelumab
- Keywords
- Trilaciclib dihydrochloride/Cosela, Metastatic Urothelial Carcinoma, Cyclin-dependent kinase 4/6 inhibitor, Immuno-oncology, Solid tumor, Chemotherapy-induced myelosuppression, Myeloprotective
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrilaciclibDrug
Also called Cosela, G1T28
Trilaciclib administered IV prior to chemotherapy and avelumab maintenance therapy on each day chemotherapy and avelumab maintenance therapy is administered.
GemcitabineDrug
Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle
CisplatinDrug
Cisplatin administered IV on Day 1 of each 21-day cycle
CarboplatinDrug
Carboplatin administered IV on Day 1 of each 21-day cycle
AvelumabDrug
Also called Bavencio
Avelumab administered IV on Day 1 of each 14-day maintenance cycle
| Study group | Role | What they receive |
|---|---|---|
| Platinum-based chemotherapy followed by avelumab maintenance therapy | Active comparator | Gemcitabine 1000 milligram per square meter (mg/m^2) + Cisplatin (70 mg/m^2) or Carboplatin (Area under the concentration-time curve [AUC] 4.5) followed by Avelumab (800 mg) Receives: Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Avelumab |
| Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy | Experimental | Trilaciclib (240 mg/m^2) + Gemcitabine (1000 mg/m^2) + Cisplatin (70 mg/m^2) or Carboplatin (AUC 4.5) followed by Trilaciclib (240 mg/m^2) + Avelumab (800 mg) Receives: Drug: Trilaciclib; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Progression-Free Survival (PFS) During Overall Study
The PFS was defined as the time from date of randomization to the date of the first documented disease progression, or death in the absence of PD for those who had a PFS event, and the time from randomization to the censoring date for those who did not have a PFS event.
Measured: From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Approximately 96 weeks
Secondary outcomes (13)
Number of Participants With Objective Response Rate (ORR) During Chemotherapy Period
The ORR defined as the percentage of participants who had an objective response (unconfirmed or confirmed) per RECIST v1.1
Measured: From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Approximately 96 weeks
Number of Participants With Objective Response Rate During Overall Treatment Period
The ORR defined as the percentage of participants who had an objective response (unconfirmed or confirmed) per RECIST v1.1
Measured: From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Approximately 96 weeks
Percentage of Participants Survived at 12 Months [Overall Survival (OS) Rate]
The OS during the study was defined as the time from the date of randomization to the date of death for participants who died in the study regardless of cause, or to the last contact date known to be alive for those who survived as of the date of data snapshot for intermediate planned analysis or final database lock for final analyses (censored cases).
Measured: From date of randomization (Day 1) up to Month 12
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. Myeloprotective effects protect the blood-forming cells in the bone marrow from the side effects of chemotherapy such as bone marrow suppression.
Measured: Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy, approximately up to 4 months
Disease Control Rate (DCR) During Maintenance Period
The DCR was defined as the percentage of participants with best overall response (BOR) of confirmed CR, confirmed PR, or SD.
Measured: From date of randomization, up to 12 cycles (21-day each) of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the participant or investigator, assessed up to 34 weeks.
Disease Control Rate During Overall Study
The DCR was defined as the percentage of participants with BOR of confirmed CR, confirmed PR, or SD.
Measured: From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Approximately 96 weeks
Duration of Response (DoR), Overall Study
The DoR was defined as the time from the date of first documented response (CR or PR) to date of first occurrence of disease progression as determined by the investigator, or death from any cause, whichever occurs first.
Measured: From date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Approximately 96 weeks
Number of Participants With Progression-Free Survival During Maintenance Period
The PFS was defined as the time from date of randomization to the date of the first documented disease progression, or death in the absence of PD for those who had a PFS event, and the time from randomization to the censoring date for those who did not have a PFS event.
Measured: From date of randomization, up to 12 cycles (21-day each) of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the participant or investigator, assessed up to 34 weeks.
Percentage of Participants With Probability of Survival at 16 Months.
The OS was defined as the time from the date of randomization to the date of death for participants who died in the study regardless of cause, or to the last contact date known to be alive for those who survived as of the date for final database lock (censored cases).
Measured: 16 months
Overall Survival During Maintenance Period
The OS was calculated as the time (months) from date of randomization to the date of death due to any cause.
Measured: From date of randomization, up to 12 cycles (21-day each) of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the participant or investigator, assessed up to 34 weeks.
Overall Survival During Overall Study
The OS was calculated as the time (months) from date of randomization to the date of death due to any cause.
Measured: From first administration of study treatment (Day 1) until 30 days after the last dose of study treatment, approximately 96 weeks.
Number of Participants With Adverse Events (AE)
An AE was defined as any untoward or unfavourable medical occurrence in a clinical research study participant, including any abnormal sign (e.g. abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participants' involvement in the research, whether or not considered related to participation in the research.
Measured: From first administration of study treatment (Day 1) until 30 days after the last dose of study treatment, approximately 96 weeks.
Number of Participants With Serious Adverse Events (SAE)
SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect.
Measured: From first administration of study treatment (Day 1) until 30 days after the last dose of study treatment, approximately 96 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2021
- Study start4 Jun 2021
- Primary completion7 Apr 2023
- Study completion1 Mar 2024
Why it stopped: Sponsor no longer pursuing trilaciclib for the indication.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Random assignment (1:1) to one of two treatment arms
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- G1 Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical study director, Study director, G1 Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04887831
- Sponsor's protocol ID
- G1T28-209
- Other IDs
- 2021-000205-24, IND: 156967
- Acronym
- PRESERVE3
- Status last verified
- Aug 2025
- First submitted
- 5 May 2021
- Last updated
- 8 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04887831
- Acronym / sponsor ID
- PRESERVE3 / G1T28-209
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor no longer pursuing trilaciclib for the indication.
- Enrolment
- 92 participants (actual)
- Lead sponsor
- G1 Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Jun 2021 (actual)
- Primary completion
- 7 Apr 2023 (actual)
- Study completion
- 1 Mar 2024 (actual)
- First posted
- 14 May 2021 (actual)
- Results
- Posted 17 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 participants receiving first-line treatment for advanced/metastatic urothelial carcinoma.
Detailed description
Participants 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.
Participants enrolled in the study will be eligible to receive 4-6 cycles of platinum-based chemotherapy, and participants 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 [SD]) 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.
Participants will be followed for survival approximately every 3 months after receiving the last dose of study medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Random assignment (1:1) to one of two treatment arms
| Arm | Type | Receives |
|---|---|---|
| Platinum-based chemotherapy followed by avelumab maintenance therapy | Active comparator | Drug: Gemcitabine, Drug: Cisplatin, Drug: Carboplatin, Drug: AvelumabGemcitabine 1000 milligram per square meter (mg/m^2) + Cisplatin (70 mg/m^2) or Carboplatin (Area under the concentration-time curve [AUC] 4.5) followed by Avelumab (800 mg) |
| Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy | Experimental | Drug: Trilaciclib, Drug: Gemcitabine, Drug: Cisplatin, Drug: Carboplatin, Drug: AvelumabTrilaciclib (240 mg/m^2) + Gemcitabine (1000 mg/m^2) + Cisplatin (70 mg/m^2) or Carboplatin (AUC 4.5) followed by Trilaciclib (240 mg/m^2) + Avelumab (800 mg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- Age ≥18 years
- Histologically documented, locally advanced (T4b, any N; or any T, N 2-3) or metastatic urothelial carcinoma (M1, Stage IV) (also termed Transitional cell carcinoma [TCC] or Urothelial cell carcinoma [UCC] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
- Measurable disease as defined by RECIST v1.1
- Considered to be eligible to receive platinum-based chemotherapy and avelumab maintenance therapy, in the Investigator's judgment
- No prior systemic therapy in the inoperable, locally advanced, or metastatic setting including chemotherapy, immune checkpoint inhibitor therapy, targeted therapy, or investigational agents
Key exclusion criteria (31 listed)
- Prior treatment with IL-2, IFN-α, 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 within 12 months prior to randomization
- Malignancies other than urothelial carcinoma within 2 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ, or low-grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (e.g., surgery, radiation, or castration), or other non-clinically significant cancers, which may be considered after discussion with the medical monitor
- Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids. Participant must be off steroids administered for brain metastases for at least 2 weeks prior to the first dose of study drugs. No stereotactic radiation within 1 week or whole-brain radiation within 14 days prior to first dose of study drugs
- Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure (≥ Class II New York Heart Association functional classification system), myocardial infarction within 6 months prior to first dose of study drugs, unstable angina, or serious cardiac arrhythmia requiring medication
- QTcF interval > 480 msec. For participants with ventricular pacemakers, QTcF > 500 msec
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrilaciclibAlso: Cosela, G1T28Trilaciclib administered IV prior to chemotherapy and avelumab maintenance therapy on each day chemotherapy and avelumab maintenance therapy is administered. | Drug | Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy |
| GemcitabineGemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle | Drug | Platinum-based chemotherapy followed by avelumab maintenance therapy, Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy |
| CisplatinCisplatin administered IV on Day 1 of each 21-day cycle | Drug | Platinum-based chemotherapy followed by avelumab maintenance therapy, Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy |
| CarboplatinCarboplatin administered IV on Day 1 of each 21-day cycle | Drug | Platinum-based chemotherapy followed by avelumab maintenance therapy, Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy |
| AvelumabAlso: BavencioAvelumab administered IV on Day 1 of each 14-day maintenance cycle | Drug | Platinum-based chemotherapy followed by avelumab maintenance therapy, Trilaciclib plus platinum-based chemotherapy followed by avelumab maintenance therapy |
Primary outcome
Number of Participants With Progression-Free Survival (PFS) During Overall Study
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. Approximately 96 weeks
The PFS was defined as the time from date of randomization to the date of the first documented disease progression, or death in the absence of PD for those who had a PFS event, and the time from randomization to the censoring date for those who did not have a PFS event.
13 secondary outcomes
Number of Participants With Objective Response Rate (ORR) During Chemotherapy Period
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. Approximately 96 weeks
Number of Participants With Objective Response Rate During Overall Treatment Period
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. Approximately 96 weeks
Percentage of Participants Survived at 12 Months [Overall Survival (OS) Rate]
Time frame: From date of randomization (Day 1) up to Month 12
Myeloprotective Effects
Time frame: Cycle 1 Day 1 (each cycle is 21 days) through treatment with platinum-based chemotherapy, approximately up to 4 months
Disease Control Rate (DCR) During Maintenance Period
Time frame: From date of randomization, up to 12 cycles (21-day each) of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the participant or investigator, assessed up to 34 weeks.
Disease Control Rate During Overall Study
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. Approximately 96 weeks
Duration of Response (DoR), Overall Study
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. Approximately 96 weeks
Number of Participants With Progression-Free Survival During Maintenance Period
Time frame: From date of randomization, up to 12 cycles (21-day each) of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the participant or investigator, assessed up to 34 weeks.
Percentage of Participants With Probability of Survival at 16 Months.
Time frame: 16 months
Overall Survival During Maintenance Period
Time frame: From date of randomization, up to 12 cycles (21-day each) of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the participant or investigator, assessed up to 34 weeks.
Overall Survival During Overall Study
Time frame: From first administration of study treatment (Day 1) until 30 days after the last dose of study treatment, approximately 96 weeks.
Number of Participants With Adverse Events (AE)
Time frame: From first administration of study treatment (Day 1) until 30 days after the last dose of study treatment, approximately 96 weeks.
Number of Participants With Serious Adverse Events (SAE)
Time frame: From first administration of study treatment (Day 1) until 30 days after the last dose of study treatment, approximately 96 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical study director study director
G1 Therapeutics, Inc.
34 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trilaciclib, Gemcitabine and Cisplatin in people with Urothelial Carcinoma and Bladder Cancer, run by G1 Therapeutics, Inc. at 34 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States, Spain, France, Georgia, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Progression-Free Survival (PFS) During Overall Study (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. Approximately 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2025.