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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of participants that sustain a response post CPI suspension
Secondary Outcome
Median Treatment Free Interval (TFI) in months
Condition
Urothelial Carcinoma
Intervention
Pembrolizumab
Study Arms / Comparison Groups
CPI therapy
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
March 23, 2020
Completion Date
December 2023
Primary Completion Date
December 2022
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Moshe Ornstein, MD, 1-866-223-8100, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04322643
Organization ID
CASE6819
Responsible Party
Sponsor
Study Sponsor
Case Comprehensive Cancer Center
Study Sponsor
Moshe Ornstein, MD, Principal Investigator, Cleveland Clinic, Case Comprehensive Cancer Center
Verification Date
May 2022