Clinical trial NCT03577132: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Urothelial Carcinoma
Keywords: neoadjuvant chemotherapy
atezolizumab
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2018-07-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective study
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: objective pathological responses (pT0 change)
timeFrame: 4weeks
Secondary outcomes:
measure: progression-free survival at 1yr
timeFrame: 1year
Other outcomes:
Locations:
Study officials:
affiliation: Seoul National University Hospital
name: Ja Hyeon Ku, M.D.,PH.D
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Duran I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE 3rd, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thastrom A, Abidoye OO, Fine GD, Bajorin DF; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 Jan 7;389(10064):67-76. doi: 10.1016/S0140-6736(16)32455-2. Epub 2016 Dec 8.
citation: Yuk HD, Jeong CW, Kwak C, Kim H, Moon KC, Ku JH. Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. BMJ Open. 2020 Oct 15;10(10):e035530. doi: 10.1136/bmjopen-2019-035530.