Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma

NCT ID: NCT04322643

Last Updated: 2025-02-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-23
• Study Completion Date: 2023-04-17

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.

Conditions

Urothelial Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab 200 mg IV over 30 minutes every 3 weeks

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 mg IV over 60 minutes every 3 weeks. (if first dose is tolerated, all subsequent infusions may be delivered over 30 minutes)

Durvalumab

Intervention Type: DRUG

Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks.

Nivolumab

Intervention Type: DRUG

Nivolumab 480mg IV over 30 minutes every 4 weeks

Avelumab

Intervention Type: DRUG

Avelumab 800 mg IV over 60 minutes every 2 weeks

Interventions

Pembrolizumab

Pembrolizumab 200 mg IV over 30 minutes every 3 weeks

Intervention Type: DRUG

Atezolizumab

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

Durvalumab

Durvalumab 10 mg/kg IV over 60 minutes every 2 weeks.

Intervention Type: DRUG

Nivolumab

Nivolumab 480mg IV over 30 minutes every 4 weeks

Intervention Type: DRUG

Avelumab

Avelumab 800 mg IV over 60 minutes every 2 weeks

Intervention Type: DRUG

Other Intervention Names

KEYTRUDA; TECENTRIQ; IMFINZI; OPDIVO; BAVENCIO

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Moshe Ornstein, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic, Case Comprehensive Cancer Center

Locations

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

CASE6819

Identifier Type: -

Identifier Source: org_study_id