The Efficacy of Neoadjuvant Atezolizumab Treatment in Patients With Advanced Urothelial Bladder Cancer

July 30, 2018 updated by: Ja Hyeon Ku, Seoul National University Hospital

The Efficacy of Neoadjuvant Atezolizumab Treatment in Patients With Advanced Urothelial Bladder Cancer According to the BASQ Classification

Recently, promising evidences that blocking PD-1 and PD-L1 is an efficacious way to treat advanced stage bladder cancer patients. Atezolimumab is the first PD-L1 inhibitor approved by US FDA for advanced UBC in June 2014. These novel agents will become the standard therapy for unhopeful UBC patients who fail to respond to cisplatin-based chemotherapy and finally, the first-line treatment would be changed from cisplatin-based chemotherapy to immune check point inhibitors for advanced UBC, particularly neoadjuvant setting.

Additionally, along with enormous analysis of genomic landscape of bladder cancer, a consensus was reached regarding the existence of a group of Basal-Squamous-like tumors - designated BASQ - characterized the high expression of KRT5/6 and KRT14 and low/undetectable expression of FOXA1 and GATA3. This novel molecular classification can improve the identification of optimal patient population for different treatment modalities. Specifically, luminal type and basal type may have different treatment response and prognosis after initial definitive treatment, such as neoadjuvant treatments.

However, there is no evidence for this topic, particularly the clinical efficacy of neoadjuvant PD-L1 inhibitors according to the BASQ classification in patients with advanced urothelial bladder cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ≥18 years of age
  • Histologically confirmed muscle-invasive urothelial carcinoma
  • Patients undergoing radical cystectomy
  • Advanced status requiring neoadjuvant systemic therapy
  • ECOG performance status score of 0 or 1
  • Adequate organ and hematologic functions
  • Available IHC data for the BASQ classification

Exclusion Criteria:

  • Non-urothelial carcinoma histology
  • Active autoimmune disease or inflammatory bowel disease
  • Prior severe or persistent immune-related adverse events
  • Previous exposure to anti-PD-1 or anti-PD-L1 therapy
  • Requirement for 10 mg/d of prednisone or equivalent
  • Inadequate liver, kidney function and hematologic dysfunction
  • Inoperable case, such as untreated CNS metastases
  • No available archival tumor tissue for evaluating the BASQ classification

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Luminal type
Luminal type in previous transurethral resection of bladder tumor pathology. Luminal type in Immunohistochemistry (KRT5/6-KRT14-FOXA1+GATA3+)
Drug: Neoadjuvant atezolizumab

Atezolimumab

  • At a fixed dose of 1200 mg as a 60-minute intravenous infusion (1st), then as a 30-minute intravenous infusion (2nd and 3rd)
  • Every 3 weeks, for a total of 3 cycles prior to radical cystectomy
Experimental: Basal typr
Basal type in previous transurethral resection of bladder tumor pathology. Basal type in Immunohistochemistry (KRT5/6+KRT14+FOXA1-GATA3-)
Drug: Neoadjuvant atezolizumab

Atezolimumab

  • At a fixed dose of 1200 mg as a 60-minute intravenous infusion (1st), then as a 30-minute intravenous infusion (2nd and 3rd)
  • Every 3 weeks, for a total of 3 cycles prior to radical cystectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
objective pathological responses (pT0 change)
Time Frame: 4weeks
Final pathology of bladder after operation (radical cystectomy)
4weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression-free survival at 1yr
Time Frame: 1year
progression-free survival at 1yr
1year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Investigators

  • Principal Investigator: Ja Hyeon Ku, M.D.,PH.D, Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

August 1, 2018

Primary Completion (Anticipated)

May 31, 2020

Study Completion (Anticipated)

May 31, 2022

Study Registration Dates

First Submitted

June 24, 2018

First Submitted That Met QC Criteria

June 24, 2018

First Posted (Actual)

July 5, 2018

Study Record Updates

Last Update Posted (Actual)

July 31, 2018

Last Update Submitted That Met QC Criteria

July 30, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SeoulNUHUro_Atezolizumab

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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