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

Hoffmann-La Roche1,004 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

1,004

Conditions

Urinary Tract Cancer

Interventions

AtezolizumabDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (175)

Outcomes

Primary Outcomes

Percentage of Participants With Adverse Events (AEs)

AEs were defined as any untoward medical occurrence in a subject administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. New disease, exacerbation of existing disease, recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test associated with symptoms or leading to a change in study/concomitant treatment or discontinuation from study drug as well as events related to protocol-mandated interventions are considered AEs.

Time frame: Baseline up to end of study (up to approximately 6 years)

Secondary Outcomes

Overall Survival (OS)

OS was defined as date of death (due to any cause) or censoring minus date of start of study treatment plus 1.

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)

PFS was defined as the date of first occurrence of tumor progression (earliest of the dates of the RECIST component indicating tumor progression) or date of death (in the absence of tumor progression) by any cause, whichever occurred first, or date of censoring minus date of start of study treatment plus 1.

Time frame: Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)

PFS as Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST)

PFS as per Modified RECIST was defined as: * date of first occurrence of tumor progression after a modified confirmed response if the participant was a responder according to modified RECIST or * date of first occurrence of tumor progression in case the participant was not a responder according to modified RECIST or * date of death (in the absence of tumor progression) by any cause, or * date of censoring whichever occurred first, minus date of start of study treatment plus 1

Data from ClinicalTrials.gov

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Inst. Alexander Fleming; Oncologia

Buenos Aires, Argentina

Hospital Aleman

Caba, Argentina

Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, Argentina

Canberra Hospital; Medical Oncology

Canberra, Australian Capital Territory, Australia

Macquarie University Hospital

Macquarie Park, New South Wales, Australia

Prince of Wales Hospital; Oncology

Randwick, New South Wales, Australia

Northern Cancer Institute

St Leonards, New South Wales, Australia

Calvary Mater Newcastle; Medical Oncology

Waratah, New South Wales, Australia

Icon Cancer Foundation

South Brisbane, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

...and 165 more locations

Time frame: Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)

Percentage of Participants With Best Overall Response (BOR) as Assessed by RECIST v1.1

BOR was assessed by the investigators according to the RECIST v1.1. BOR was defined as a complete response (CR) or partial response (PR) determined on two consecutive investigator assessments \>= 4 weeks apart in participants with measurable disease at baseline. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 millimeters (mm); PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study.

Time frame: Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)

Percentage of Participants With BOR as Assessed by Modified RECIST

BOR was assessed by the investigators according to the modified RECIST. BOR was defined as complete response (CR) or partial response (PR). CR includes complete disappearance of all tumor lesions and no new measurable or unmeasurable lesions confirmed by a consecutive assessment \>=4 weeks from the first documented date. PR is a decrease in the sum of the diameters of all target and all new measurable lesions \>=30%, relative to baseline, in the absence of CR confirmed by a consecutive assessment \>=4 weeks from the first documented date. The assessment of BOR included post-screening RECIST assessments obtained up to: 1) death from any cause, 2) last evaluable RECIST assessment in the absence of death, 3) start of a subsequent anti-cancer therapy, whichever occurred first.

Time frame: Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)

Percentage of Participants With Disease Control as Assessed by RECIST v1.1

Disease control was determined separately on disease status using RECIST v1.1 by the investigator. Disease control rate was defined as the sum of the complete response, partial response, and stable disease rates.

Time frame: Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)

Percentage of Participants With Disease Control as Assessed by Modified RECIST

Disease control was determined separately on disease status using modified RECIST by the investigator. Disease control rate was defined as the sum of the complete response, partial response, and stable disease rates.

Time frame: Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)

Duration of Response (DOR) as Assessed by RECIST v1.1

Duration of response was determined separately on disease status using RECIST v1.1 by the investigator. For overall responders, DoR was defined as the time from the date of first occurrence of a confirmed response (complete response or partial response) to date of tumor progression or death from any cause, or to censoring date: 1) end of response coincided with the date of tumor progression or death (in the absence of tumor progression) used for the PFS endpoint, 2) for a participant without disease progression or death following a response, the censored end of response coincided with the PFS censoring date (that was latest RECIST assessment or start of subsequent cancer therapy, whichever occurred first).

Time frame: Time from first occurrence of a documented response to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)

DOR as Assessed by Modified RECIST

Duration of response was determined separately on disease status using modified RECIST by the investigator. For overall responders, DoR was defined as the time from the date of first occurrence of a confirmed response (complete response or partial response) to date of tumor progression following that confirmed response or death from any cause, or to censoring date: 1) end of response was the date of tumor progression after that confirmed response or death (in the absence of tumor progression), 2) for a participant without disease progression or death following a response, the censored end of response was the latest RECIST assessment or start of subsequent cancer therapy, whichever occurred first.

Time frame: Time from first occurrence of a documented response to disease progression or death from any cause, whichever occurred 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

The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores were averaged and transformed to 0 - 100 scale. Higher scores on the global health status and functional scales indicated better health status/function. Higher scores on the symptoms scales and symptom items indicated greater symptom burden.

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

The EuroQol 5-Dimension Questionnaire (EQ-5D-5L) is a self-report health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are two components to the EuroQol EQ-5D: 1) five health dimensions that assess mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; 2) a visual analogue scale (VAS) that measures health state. There are 5 response levels for each dimension (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems) with the highest level representing the worst outcome. The VAS is scored on a scale from 0 to 100, with 0 representing the worst imaginable health and 100 representing the best imaginable health.