Brief Title
The Efficacy of Neoadjuvant Atezolizumab Treatment in Patients With Advanced Urothelial Bladder Cancer
Official Title
The Efficacy of Neoadjuvant Atezolizumab Treatment in Patients With Advanced Urothelial Bladder Cancer According to the BASQ Classification
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.
Study Type
Interventional
Primary Outcome
objective pathological responses (pT0 change)
Secondary Outcome
progression-free survival at 1yr
Condition
Urothelial Carcinoma
Intervention
Neoadjuvant atezolizumab
Study Arms / Comparison Groups
Luminal type
Description: Luminal type in previous transurethral resection of bladder tumor pathology. Luminal type in Immunohistochemistry (KRT5/6-KRT14-FOXA1+GATA3+)
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
August 1, 2018
Completion Date
May 31, 2022
Primary Completion Date
May 31, 2020
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Ja Hyeon Ku, M.D.,PH.D, +82-2-2072-0361, [email protected]
Administrative Informations
NCT ID
NCT03577132
Organization ID
SeoulNUHUro_Atezolizumab
Responsible Party
Principal Investigator
Study Sponsor
Seoul National University Hospital
Study Sponsor
Ja Hyeon Ku, M.D.,PH.D, Principal Investigator, Seoul National University Hospital
Verification Date
July 2018