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

Sponsor

Seoul National University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03577132

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Urothelial Carcinoma	Drug: Neoadjuvant atezolizumab	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective studyProspective study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2018

Anticipated Primary Completion Date :

May 31, 2020

Anticipated Study Completion Date :

May 31, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

objective pathological responses (pT0 change) [4weeks]
Final pathology of bladder after operation (radical cystectomy)

Secondary Outcome Measures

progression-free survival at 1yr [1year]
progression-free survival at 1yr

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Seoul National University Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Ja Hyeon Ku, Professor, MD., PHD., Seoul National University Hospital

ClinicalTrials.gov Identifier:

NCT03577132

Other Study ID Numbers:

SeoulNUHUro_Atezolizumab

First Posted:

Jul 5, 2018

Last Update Posted:

Jul 31, 2018

Last Verified:

Jul 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Ja Hyeon Ku, Professor, MD., PHD., Seoul National University Hospital

neoadjuvant chemotherapy

atezolizumab

Additional relevant MeSH terms:

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Atezolizumab

Study Results

No Results Posted as of Jul 31, 2018