Back to resultsIntermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma
Primary Purpose
Urothelial Carcinoma
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Atezolizumab
Durvalumab
Nivolumab
Avelumab
Sponsored by
About this trial
This is an interventional treatment trial for Urothelial Carcinoma
Eligibility Criteria
Inclusion Criteria:
- 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)
- 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)
Exclusion Criteria:
- 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.
Sites / Locations
- Cleveland Clinic, Case Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CPI therapy
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Median Treatment Free Interval (TFI) in months
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)
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)
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)
Overall Survival (OS) defined as the time from randomization to death due to any cause
Full Information
NCT ID
NCT04322643
First Posted
March 24, 2020
Last Updated
October 4, 2023
Sponsor
Case Comprehensive Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT04322643
Brief Title
Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma
Official Title
A Phase II Study of Intermittent Checkpoint Inhibitor Therapy in Patients With Advanced Urothelial Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 23, 2020 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CPI therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
KEYTRUDA
Intervention Description
Pembrolizumab 200 mg IV over 30 minutes every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
TECENTRIQ
Intervention Description
Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes)
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
IMFINZI
Intervention Description
Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
OPDIVO
Intervention Description
Nivolumab 480mg IV over 30 minutes every 4 weeks
Intervention Type
Drug
Intervention Name(s)
Avelumab
Other Intervention Name(s)
BAVENCIO
Intervention Description
Avelumab 800 mg IV over 60 minutes every 2 weeks
Primary Outcome Measure Information:
Title
Number of participants that sustain a response post CPI suspension
Description
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.
Time Frame
at 36 weeks post CPI suspension
Secondary Outcome Measure Information:
Title
Median Treatment Free Interval (TFI) in months
Description
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.
Time Frame
up to 36 weeks from end of treatment, an average of 24 weeks
Title
Overall response rate (ORR)
Description
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
Time Frame
up to 36 weeks from end of treatment, an average of 24 weeks
Title
Progression free survival (PFS)
Description
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.
Time Frame
up to 36 weeks from end of treatment, an average of 24 weeks
Title
Overall Survival (OS)
Description
Overall Survival (OS) defined as the time from randomization to death due to any cause
Time Frame
up to 36 weeks from end of treatment, an average of 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
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)
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Moshe Ornstein, MD
Organizational Affiliation
Cleveland Clinic, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Summary results are shared in publications
Learn more about this trial
Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma
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