Intermittent Checkpoint Inhibitor Therapy In Patients With Advanced Urothelial Carcinoma

NCT04322643 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE6819
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  At 36 weeks post CPI suspension

Secondary Outcomes (4)

• Median Treatment Free Interval (TFI) in Weeks

  Up to 36 weeks from end of treatment, through study completion an average of 160 weeks

• Overall Response Rate (ORR)

  Up to 36 weeks from end of treatment, through study completion an average of 160 weeks

• Number of Participants With Progression Free Survival (PFS)

  Up to 36 weeks from end of treatment, through study completion an average of 160 weeks

• Number of Participants With Overall Survival (OS)

  Up to 36 weeks from end of treatment, through study completion an average of 160 weeks

Study Arms (1)

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.

Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Durvalumab; Drug: Nivolumab; Drug: Avelumab

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg IV over 30 minutes every 3 weeks

Also known as: KEYTRUDA

CPI therapy

Atezolizumab 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)

Also known as: TECENTRIQ

CPI therapy

Durvalumab DRUG

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

Also known as: IMFINZI

CPI therapy

Nivolumab DRUG

Nivolumab 480mg IV over 30 minutes every 4 weeks

Also known as: OPDIVO

CPI therapy

Avelumab DRUG

Avelumab 800 mg IV over 60 minutes every 2 weeks

Also known as: BAVENCIO

CPI therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

pembrolizumab; atezolizumab; durvalumab; Nivolumab; avelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

This study was terminated prematurely due to low enrollment and the changes in the treatment landscape of advanced urothelial carcinoma. Due to premature trial closure, data were incompletely collected and analyzed. There are no plans for future analysis. The outcome measure data is only based on the information that was collected for four participants at the time of study termination.

Results Point of Contact

• Title: Dr. Moshe Ornstein
• Organization: Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

TaussigResearch@ccf.org

866-223-8100

Study Officials

• Moshe Ornstein, MD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 26, 2020
• Study Start: March 23, 2020
• Primary Completion: August 8, 2022
• Study Completion: April 17, 2023
• Last Updated: February 25, 2025
• Results First Posted: February 25, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)