Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma
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|ClinicalTrials.gov Identifier: NCT04322643|
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : June 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|Urothelial Carcinoma||Drug: Pembrolizumab Drug: Atezolizumab Drug: Durvalumab Drug: Nivolumab Drug: Avelumab||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Intermittent Checkpoint Inhibitor Therapy in Patients With Advanced Urothelial Carcinoma|
|Actual Study Start Date :||March 23, 2020|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||May 2021|
Experimental: CPI therapy
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.
Pembrolizumab 200 mg IV over 30 minutes every 3 weeks
Other Name: KEYTRUDA
Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes)
Other Name: TECENTRIQ
Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks.
Other Name: IMFINZI
Nivolumab 480mg IV over 30 minutes every 4 weeks
Other Name: OPDIVO
Avelumab 800 mg IV over 60 minutes every 2 weeks
Other Name: BAVENCIO
- 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.
- Median Treatment Free Interval (TFI) in months [ Time Frame: up to 36 weeks from end of treatment, an average of 24 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.
- Overall response rate (ORR) [ Time Frame: up to 36 weeks from end of treatment, an average of 24 weeks ]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
- Progression free survival (PFS) [ Time Frame: up to 36 weeks from end of treatment, an average of 24 weeks ]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.
- Overall Survival (OS) [ Time Frame: up to 36 weeks from end of treatment, an average of 24 weeks ]Overall Survival (OS) defined as the time from randomization to death due to any cause
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): NCT04322643
|Contact: Moshe Ornstein, MD||1-866-223-8100||TaussigResearch@ccf.org|
|United States, Ohio|
|Cleveland Clinic, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Moshe Ornstein, MD 866-223-8100 TaussigResearch@ccf.org|
|Principal Investigator: Moshe Ornstein, MD|
|Principal Investigator:||Moshe Ornstein, MD||Cleveland Clinic, Case Comprehensive Cancer Center|