Urothelial CarcinomaPhase 2NCT04322643
Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma
A Phase 2 study testing Pembrolizumab, Atezolizumab and Durvalumab in people with Urothelial Carcinoma, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and effectiveness of immunotherapy (checkpoint inhibitor therapy) in advanced bladder cancer when given intermittently. An unanswered question with the use of CPI (checkpoint inhibitor) is the duration of therapy required for optimal clinical benefit. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- Pembrolizumab, Atezolizumab and Durvalumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Mar 2020to 17 Apr 2023
- 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
- Men and women ≥ 18 years of age.
- Histological confirmation of urothelial carcinoma (any histology)
- Advanced or metastatic urothelial carcinoma.
- Measurable disease as defined by RECIST 1.1 criteria
- Has received at least 24 weeks (+/- 4 weeks) on CPI therapy per standard of care (SOC) for advanced urothelial carcinoma
- Karnofsky Performance Score (KPS) ≥70% (for more information on KPS, please see: http://www.npcrc.org/files/news/karnofsky_performance_scale.pdf)
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- Willing and able to provide informed consent.
- Laboratory criteria for study entry must meet the following criteria:
- Serum creatinine ≤ 2 x ULN OR CrCl ≥ 30 mL/min (measured or calculated using the Cockcroft-Gault formula).
- Hb ≥ 8.0g/dL
- AST and ALT ≤ 3.0 x ULN
- Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
Who cannot join
- History of severe hypersensitivity reaction to any monoclonal antibody.
- Patients are excluded if they have known HIV/AIDS.
- Major surgery (eg, cystectomy) less than 28 days prior to the first dose of study drug.
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 7 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
- Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
- Pregnant women are excluded from this study because animal studies have demonstrated that PD-1/PD-L1 inhibitors can cause fetal harm when administered to pregnant women. Breastfeeding women are excluded from this study because PD-1/PD-L1 inhibitors may be excreted in human milk and the potential for serious adverse reactions in nursing infants.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Phase II Study of Intermittent Checkpoint Inhibitor Therapy in Patients With Advanced Urothelial Carcinoma
The purpose of this study is to test the safety and effectiveness of immunotherapy (checkpoint inhibitor therapy) in advanced bladder cancer when given intermittently. An unanswered question with the use of CPI (checkpoint inhibitor) is the duration of therapy required for optimal clinical benefit. In the absence of progressive disease or unacceptable toxicities, there are currently no specified criteria for treatment discontinuation. Strategies to reduce toxicity and maximize benefit require investigation. Thus, novel dosing schedules, early discontinuation considerations, and biomarkers of response are needed to identify patients who can sustain disease regression while off of therapy.
Read the detailed description
A phase II study design to investigate the use of any CPI on an intermittent dosing schedule. Patients with advanced urothelial carcinoma (aUC) who treatment refractory or cisplatin ineligible will receive CPI of choice as per standard dosing. Patients who have initial >/=10% tumor burden reduction will discontinue the CPI until they experience a >/=20% disease progression following 24 weeks +/- 4 weeks of immunotherapy, at which time CPI therapy will be restarted.
All patients who do not meet criteria for the CPI intermittent phase of the study will be treated until unacceptable toxicity or RECIST-defined PD. Patients with RECIST-defined PD may continue CPI therapy at the discretion of the treating MD. These patients will continue with normal imaging every 12 weeks. In cases where a patient is continued on therapy after PD and develops subsequent PD (> 20% increase in sum of target lesions compared to the initial PD tumor measurements, the patient will come off study).
Patients who meet criteria for the intermittent phase (i.e., have >/=10% tumor burden reduction) will not receive CPI therapy. Imaging will continue per protocol (every 12 weeks from the initial date they stopped CPI therapy). Patients who have RECIST defined PD on the intermittent phase should reinitiate CPI therapy. Patients who have a subsequent decrease in tumor burden >/=10% can then restart CPI therapy as per protocol.
- Conditions
- Urothelial Carcinoma
- Being tested
- Pembrolizumab, Atezolizumab, Durvalumab, Nivolumab, Avelumab
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called KEYTRUDA
Pembrolizumab 200 mg IV over 30 minutes every 3 weeks
AtezolizumabDrug
Also called TECENTRIQ
Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes)
DurvalumabDrug
Also called IMFINZI
Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks.
NivolumabDrug
Also called OPDIVO
Nivolumab 480mg IV over 30 minutes every 4 weeks
AvelumabDrug
Also called BAVENCIO
Avelumab 800 mg IV over 60 minutes every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| CPI therapy | Experimental | Patients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Receives: Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Durvalumab; Drug: Nivolumab; Drug: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Sustain a Response Post CPI Suspension
Efficiency, as measured by number of participants that sustain a response post CPI suspension. Response is defined as tumor burden reduction of 10% or greater. Response is measured based on RECIST criteria version 1.1. RECIST 1.1 responses include Complete Response (CR) which is defined as disappearance of all lesions and pathologic lymph nodes; Partial Response (PR) defined as ≥ 30% decrease SLD, no new lesions, no progression of non-target lesions; Stable disease (SD) which is defined as no partial or complete responses; or Progressive disease (PD) defined as ≥ 20% increase SLD compared to smallest SLD in study, or progression of non-target lesions, or new lesions.
Measured: At 36 weeks post CPI suspension
Secondary outcomes (4)
Median Treatment Free Interval (TFI) in Weeks
Median and range TFI in months. Participants will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. Participants with a documented increase in ≥ 20% tumor burden (RECIST 1.1 PD) will re-initiate CPI. For those patients who continue to have response, they will remain off therapy.
Measured: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks
Overall Response Rate (ORR)
Response to re-initiation of CPI therapy as measured by overall response rate (ORR) defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1
Measured: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks
Number of Participants With Progression Free Survival (PFS)
Progression free survival (PFS) defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first as assessed by RECIST 1.1 criteria. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm and the appearance of ≥1 new lesions is also considered PD.
Measured: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks
Number of Participants With Overall Survival (OS)
Overall Survival (OS) defined as the time from randomization to death due to any cause
Measured: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2020
- Study start23 Mar 2020
- Primary completion8 Aug 2022
- Study completion17 Apr 2023
Why it stopped: PI preference
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.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Moshe Ornstein, MD, Principal investigator, Cleveland Clinic, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04322643
- Sponsor's protocol ID
- CASE6819
- Status last verified
- Feb 2025
- First submitted
- 24 Mar 2020
- Last updated
- 25 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Summary results are shared in publications
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Intermittent Checkpoint Inhibitor Therapy in Patients With Advanced Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT04322643
- Acronym / sponsor ID
- CASE6819
- Conditions
- Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI preference
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 23 Mar 2020 (actual)
- Primary completion
- 8 Aug 2022 (actual)
- Study completion
- 17 Apr 2023 (actual)
- First posted
- 26 Mar 2020 (actual)
- Results
- Posted 25 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety and effectiveness of immunotherapy (checkpoint inhibitor therapy) in advanced bladder cancer when given intermittently. An unanswered question with the use of CPI (checkpoint inhibitor) is the duration of therapy required for optimal clinical benefit. In the absence of progressive disease or unacceptable toxicities, there are currently no specified criteria for treatment discontinuation. Strategies to reduce toxicity and maximize benefit require investigation. Thus, novel dosing schedules, early discontinuation considerations, and biomarkers of response are needed to identify patients who can sustain disease regression while off of therapy.
Detailed description
A phase II study design to investigate the use of any CPI on an intermittent dosing schedule. Patients with advanced urothelial carcinoma (aUC) who treatment refractory or cisplatin ineligible will receive CPI of choice as per standard dosing. Patients who have initial >/=10% tumor burden reduction will discontinue the CPI until they experience a >/=20% disease progression following 24 weeks +/- 4 weeks of immunotherapy, at which time CPI therapy will be restarted.
All patients who do not meet criteria for the CPI intermittent phase of the study will be treated until unacceptable toxicity or RECIST-defined PD. Patients with RECIST-defined PD may continue CPI therapy at the discretion of the treating MD. These patients will continue with normal imaging every 12 weeks. In cases where a patient is continued on therapy after PD and develops subsequent PD (> 20% increase in sum of target lesions compared to the initial PD tumor measurements, the patient will come off study).
Patients who meet criteria for the intermittent phase (i.e., have >/=10% tumor burden reduction) will not receive CPI therapy. Imaging will continue per protocol (every 12 weeks from the initial date they stopped CPI therapy). Patients who have RECIST defined PD on the intermittent phase should reinitiate CPI therapy. Patients who have a subsequent decrease in tumor burden >/=10% can then restart CPI therapy as per protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CPI therapy | Experimental | Drug: Pembrolizumab, Drug: Atezolizumab, Drug: Durvalumab, Drug: Nivolumab, Drug: AvelumabPatients will be treated with CPI therapy for at least 24 weeks (+/- 4 weeks) as per standard of care (SOC), at which time those with a tumor burden reduction of 10% or greater will suspend CPI therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Men and women ≥ 18 years of age.
- Histological confirmation of urothelial carcinoma (any histology)
- Advanced or metastatic urothelial carcinoma.
- Measurable disease as defined by RECIST 1.1 criteria
- Has received at least 24 weeks (+/- 4 weeks) on CPI therapy per standard of care (SOC) for advanced urothelial carcinoma
Key exclusion criteria (6 listed)
- History of severe hypersensitivity reaction to any monoclonal antibody.
- Patients are excluded if they have known HIV/AIDS.
- Major surgery (eg, cystectomy) less than 28 days prior to the first dose of study drug.
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 7 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
- Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
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 |
|---|---|---|
| PembrolizumabAlso: KEYTRUDAPembrolizumab 200 mg IV over 30 minutes every 3 weeks | Drug | CPI therapy |
| AtezolizumabAlso: TECENTRIQAtezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes) | Drug | CPI therapy |
| DurvalumabAlso: IMFINZIDurvalumab 10 mg/kg IV over 60 minutes every 2 weeks. | Drug | CPI therapy |
| NivolumabAlso: OPDIVONivolumab 480mg IV over 30 minutes every 4 weeks | Drug | CPI therapy |
| AvelumabAlso: BAVENCIOAvelumab 800 mg IV over 60 minutes every 2 weeks | Drug | CPI therapy |
Primary outcome
Number of Participants That Sustain a Response Post CPI Suspension
Time frame: At 36 weeks post CPI suspension
Efficiency, as measured by number of participants that sustain a response post CPI suspension. Response is defined as tumor burden reduction of 10% or greater. Response is measured based on RECIST criteria version 1.1. RECIST 1.1 responses include Complete Response (CR) which is defined as disappearance of all lesions and pathologic lymph nodes; Partial Response (PR) defined as ≥ 30% decrease SLD, no new lesions, no progression of non-target lesions; Stable disease (SD) which is defined as no partial or complete responses; or Progressive disease (PD) defined as ≥ 20% increase SLD compared to smallest SLD in study, or progression of non-target lesions, or new lesions.
4 secondary outcomes
Median Treatment Free Interval (TFI) in Weeks
Time frame: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks
Overall Response Rate (ORR)
Time frame: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks
Number of Participants With Progression Free Survival (PFS)
Time frame: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks
Number of Participants With Overall Survival (OS)
Time frame: Up to 36 weeks from end of treatment, through study completion an average of 160 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Summary results are shared in publications
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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.
Moshe Ornstein, MD principal investigator
Cleveland Clinic, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Atezolizumab and Durvalumab in people with Urothelial Carcinoma, run by Case Comprehensive Cancer Center at 1 site in United States.
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 12 inclusion and 6 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 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 25 Feb 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 That Sustain a Response Post CPI Suspension (time frame: At 36 weeks post CPI suspension). 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 25 Feb 2025.