NCT03577132

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Aug 2018

Longer than P75 for not_applicable

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 24, 2018

Completed
11 days until next milestone

First Posted

Study publicly available on registry

July 5, 2018

Completed
27 days until next milestone

Study Start

First participant enrolled

August 1, 2018

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2020

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2022

Completed
Last Updated

July 31, 2018

Status Verified

July 1, 2018

Enrollment Period

1.8 years

First QC Date

June 24, 2018

Last Update Submit

July 30, 2018

Conditions

Urothelial Carcinoma

Keywords

neoadjuvant chemotherapyatezolizumab

Outcome Measures

Primary Outcomes (1)

  • objective pathological responses (pT0 change)

    Final pathology of bladder after operation (radical cystectomy)

    4weeks

Secondary Outcomes (1)

  • progression-free survival at 1yr

    1year

Study Arms (2)

Luminal type

EXPERIMENTAL

Luminal type in previous transurethral resection of bladder tumor pathology. Luminal type in Immunohistochemistry (KRT5/6-KRT14-FOXA1+GATA3+)

Drug: Neoadjuvant atezolizumab

Basal typr

EXPERIMENTAL

Basal type in previous transurethral resection of bladder tumor pathology. Basal type in Immunohistochemistry (KRT5/6+KRT14+FOXA1-GATA3-)

Drug: Neoadjuvant atezolizumab

Interventions

Neoadjuvant atezolizumabDRUG

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

Basal typrLuminal type

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (6)

  • Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. doi: 10.1056/NEJMoa022148.

    PMID: 12944571BACKGROUND

  • von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20;23(21):4602-8. doi: 10.1200/JCO.2005.07.757.

    PMID: 16034041BACKGROUND

  • Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014 Mar 20;507(7492):315-22. doi: 10.1038/nature12965. Epub 2014 Jan 29.

    PMID: 24476821BACKGROUND

  • Choi W, Czerniak B, Ochoa A, Su X, Siefker-Radtke A, Dinney C, McConkey DJ. Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer. Nat Rev Urol. 2014 Jul;11(7):400-10. doi: 10.1038/nrurol.2014.129. Epub 2014 Jun 24.

    PMID: 24960601BACKGROUND

  • 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.

    PMID: 27939400BACKGROUND

  • 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.

    PMID: 33060077DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasms

Study Officials

  • Ja Hyeon Ku, M.D.,PH.D

    Seoul National University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ja Hyeon Ku, M.D.,PH.D

CONTACT

+82-2-2072-0361randyku@hanmail.net

Hyeongdong Yuk, M.D.

CONTACT

+82-2-2072-1968hinayuk@naver.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Prospective study
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, MD., PHD.

Study Record Dates

First Submitted

June 24, 2018

First Posted

July 5, 2018

Study Start

August 1, 2018

Primary Completion

May 31, 2020

Study Completion

May 31, 2022

Last Updated

July 31, 2018

Record last verified: 2018-07

Data Sharing

IPD Sharing
Will not share