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

NCT ID: NCT03577132

Last Updated: 2018-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-01

Study Completion Date

2022-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Urothelial Carcinoma

Keywords

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neoadjuvant chemotherapy atezolizumab

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Prospective study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Luminal type

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

Group Type EXPERIMENTAL

Neoadjuvant atezolizumab

Intervention Type DRUG

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 typr

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

Group Type EXPERIMENTAL

Neoadjuvant atezolizumab

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Seoul National University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ja Hyeon Ku

Professor, MD., PHD.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Central Contacts

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

Role: CONTACT

Phone: +82-2-2072-0361

Email: [email protected]

Hyeongdong Yuk, M.D.

Role: CONTACT

Phone: +82-2-2072-1968

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 12944571 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16034041 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24476821 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24960601 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27939400 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33060077 (View on PubMed)

Other Identifiers

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SeoulNUHUro_Atezolizumab

Identifier Type: -

Identifier Source: org_study_id