A Study of Atezolizumab in Locally Advanced or Metastatic Urothelial or Non-Urothelial Carcinoma of the Urinary Tract

• ClinicalTrials.gov Identifier: NCT02928406
• Recruitment Status: Completed
• First Posted: October 10, 2016
• Last Update Posted: December 22, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: October 7, 2016
• First Posted Date: October 10, 2016
• Last Update Posted Date: December 22, 2022
• Actual Study Start Date: November 30, 2016
• Actual Primary Completion Date: December 12, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 7, 2017): Percentage of Participants With Adverse Events [ Time Frame: Baseline up to end of study (up to approximately 6 years) ]
• Original Primary Outcome Measures (submitted: October 7, 2016): Percentage of Participants With Adverse event [ Time Frame: Baseline up to approximately 6 years ]

Current Secondary Outcome Measures (submitted: November 7, 2017)

• Overall Survival (OS) [ Time Frame: Randomization until death from any cause (up to approximately 6 years) ]
• Progression Free Survival (PFS) as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• PFS as per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST) [ Time Frame: Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• Percentage of Participants With Best Overall Response as Assessed by RECIST v1.1 [ Time Frame: Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• Percentage of Participants With Best Overall Response as Assessed by Modified RECIST [ Time Frame: Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• Percentage of Participants With Disease Control as Assessed by RECIST v1.1 [ Time Frame: Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• Percentage of Participants With Disease Control as Assessed by Modified RECIST [ Time Frame: Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• Duration of Response as Assessed by RECIST v1.1 [ Time Frame: Time from first occurrence of a documented response to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• Duration of Response as Assessed by Modified RECIST [ Time Frame: Time from first occurrence of a documented response to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• Change From Baseline in Health-Related Quality of Life (HRQoL), as Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score [ Time Frame: Baseline, Day 1 of Cycles 1, 2, 3 and thereafter every 9 weeks for 54 weeks from study treatment start; and then every 12 weeks until progression/study discontinuation (up to approximately 6 years) (Cycle length = 21 days) ]
• Change from Baseline in European Quality of Life (EuroQoL) Group 5-Dimension 5-Level (EQ-5D-5L) Self Report Questionnaire Health Utility Score [ Time Frame: Baseline, Day 1 of Cycles 1, 2, 3 and thereafter every 9 weeks for 54 weeks from study treatment start; and then every 12 weeks until progression/study discontinuation (up to approximately 6 years) (Cycle length = 21 days) ]

Original Secondary Outcome Measures (submitted: October 7, 2016)

• Overall Survival (OS) [ Time Frame: Randomization up to death by any cause (up to approximately 6 years) ]
• Progression Free Survival (PFS) as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: Randomization up to disease progression or death, whichever occurs first (up to approximately 6 years) ]
• Percentage of Participants With Best Overall Response as Assessed by RECIST v1.1 [ Time Frame: Randomization up to disease progression or death, whichever occurs first (up to approximately 6 years) ]
• Percentage of Participants With Disease Control as Assessed by RECIST v1.1 [ Time Frame: Randomization up to disease progression or death, whichever occurs first (up to approximately 6 years) ]
• Duration of Response as Assessed by RECIST v1.1 [ Time Frame: First occurrence of a documented response to disease progression or death from any cause, whichever occurs first (up to approximately 6 years) ]
• Change From Baseline in Health-Related Quality of Life (HRQoL), as Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score [ Time Frame: Baseline, Day 1 of Cycles 1, 2, 3 and thereafter every 9 weeks for 54 weeks from study treatment start; and then every 12 weeks until progression/study discontinuation (up to approximately 6 years) (Cycle length = 21 days) ]
• Change from Baseline in EuroQoL (European Quality of Life) Group 5-Dimension 5-Level Self Report Questionnaire (EQ-5D-5L) Health Utility Score [ Time Frame: Baseline, Day 1 of Cycles 1, 2, 3 and thereafter every 9 weeks for 54 weeks from study treatment start; and then every 12 weeks until progression/study discontinuation (up to approximately 6 years) (Cycle length = 21 days) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Atezolizumab in Locally Advanced or Metastatic Urothelial or Non-Urothelial Carcinoma of the Urinary Tract
• Official Title: An Open Label, Single Arm, Multicenter, Safety Study of Atezolizumab in Locally Advanced or Metastatic Urothelial or Non-Urothelial Carcinoma of the Urinary Tract
• Brief Summary: This Phase IIIb, multicenter study will assess the safety of atezolizumab as second- to fourth-line treatment for participants with locally advanced or metastatic urothelial or non-urothelial cancer of the urinary tract in addition to evaluate the efficacy of atezolizumab and potential tumor biomarkers associated with atezolizumab.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urinary Tract Cancer

Intervention

Drug: Atezolizumab

Atezolizumab 1200 milligrams (mg) will be administered by intravenous (IV) infusion Q3W.

Other Name: MPDL3280A

Study Arms

Experimental: Atezolizumab

Participants will receive atezolizumab every 3 weeks (Q3W) until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Intervention: Drug: Atezolizumab

Publications *

• Bamias A, Merseburger AS, Loriot Y, James N, Choy E, Castellano D, Lopez-Rios F, Calabro F, Kramer M, de Velasco G, Zakopoulou R, Tzannis K, Sternberg CN. SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy. ESMO Open. 2021 Jun;6(3):100152. doi: 10.1016/j.esmoop.2021.100152. Epub 2021 May 10.
• Merseburger AS, Castellano D, Powles T, Loriot Y, Retz M, Voortman J, Huddart RA, Gedye C, Van Der Heijden MS, Gurney H, Ong M, de Ducla S, Pavlova J, Fear S, Sternberg CN. Safety and Efficacy of Atezolizumab in Understudied Populations with Pretreated Urinary Tract Carcinoma: Subgroup Analyses of the SAUL Study in Real-World Practice. J Urol. 2021 Aug;206(2):240-251. doi: 10.1097/JU.0000000000001768. Epub 2021 Apr 9.
• Loriot Y, Sternberg CN, Castellano D, Oosting SF, Dumez H, Huddart R, Vianna K, Alonso Gordoa T, Skoneczna I, Fay AP, Nole F, Massari F, Brasiuniene B, Maroto P, Fear S, Di Nucci F, de Ducla S, Choy E. Safety and efficacy of atezolizumab in patients with autoimmune disease: Subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma. Eur J Cancer. 2020 Oct;138:202-211. doi: 10.1016/j.ejca.2020.07.023. Epub 2020 Sep 6.
• Cathomas R, Schardt J, Pless M, Llado A, Mach N, Riklin C, Haefeli J, Fear S, Stenner F. Swiss experience of atezolizumab for platinum-pretreated urinary tract carcinoma: the SAUL study in real-world practice. Swiss Med Wkly. 2020 May 4;150:w20223. doi: 10.4414/smw.2020.20223. eCollection 2020 May 4.
• Sternberg CN, Loriot Y, James N, Choy E, Castellano D, Lopez-Rios F, Banna GL, De Giorgi U, Masini C, Bamias A, Garcia Del Muro X, Duran I, Powles T, Gamulin M, Zengerling F, Geczi L, Gedye C, de Ducla S, Fear S, Merseburger AS. Primary Results from SAUL, a Multinational Single-arm Safety Study of Atezolizumab Therapy for Locally Advanced or Metastatic Urothelial or Nonurothelial Carcinoma of the Urinary Tract. Eur Urol. 2019 Jul;76(1):73-81. doi: 10.1016/j.eururo.2019.03.015. Epub 2019 Mar 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 25, 2022): 1005
• Original Estimated Enrollment (submitted: October 7, 2016): 1000
• Actual Study Completion Date: December 12, 2022
• Actual Primary Completion Date: December 12, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participants with histologically documented locally advanced (tumor [T] 4b, any node [N]; or any T, N 2-3) or metastatic (M1, Stage IV) urothelial or non-urothelial carcinoma of the urinary tract
• Participants with measurable and/or non-measurable disease according to RECIST v1.1
• Participants must have progressed during or following treatment with at least one prior (and not more than 3) treatments for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract
• If available, a representative formalin-fixed paraffin-embedded (FFPE) tumor specimen block should be submitted
• Eastern cooperative oncology group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

• Treatment with more than three prior lines of systemic therapy for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract

• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to study treatment initiation

  1. Participants who were in another clinical trial with therapeutic intent within 4 weeks of study treatment initiation but were not on active drug in that prior trial are eligible
  2. Participants who were in another clinical trial with therapeutic intent within 4 weeks of study treatment initiation but were in the follow-up phase of that prior trial and had stopped receiving active drug 4 or more weeks before study treatment initiation are eligible
• Malignancies other than the one studied in this protocol within 5 years prior to Cycle 1, Day 1
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol
• Significant renal disorder indicating a need for renal transplant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Croatia, Czechia, Denmark, Estonia, Germany, Greece, Hungary, India, Ireland, Italy, Lebanon, Lithuania, Netherlands, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Slovakia, Spain, Swaziland, Switzerland, Taiwan, United Kingdom
• Removed Location Countries: Czech Republic, Egypt, Turkey

Administrative Information

• NCT Number: NCT02928406
• Other Study ID Numbers: MO29983; 2016-002625-11 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: December 2022