Trial from ClinicalTrials.gov

For full trial details, please see the original record at



Trial ID
NCT02450331
Ethics application status
Date submitted
19/05/2015
Date registered
19/05/2015
Date last updated
1/08/2017

Titles & IDs
Public title
A Study of Atezolizumab Versus Observation as Adjuvant Therapy in Participants With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection [IMvigor010]
Scientific title
A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection
Secondary ID [1] 0 0
2014-005603-25
Secondary ID [2] 0 0
WO29636
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Transitional Cell 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: drugs - Atezolizumab

Experimental: Atezolizumab - Participants will receive intravenous (IV) atezolizumab on Day 1 of each 21-day cycle for 16 cycles (up to 1 year).

No Intervention: Observation - Participants will undergo observation starting on Day 1 for 16 cycles (up to 1 year).


Treatment: drugs: Atezolizumab
Atezolizumab will be administered at a dose of 1200 milligrams (mg).

Intervention code [1] 0 0
Treatment: drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease-Free Survival (DFS), as Assessed by Investigator - DFS is defined as the time from randomization to the time of first occurrence of a DFS event. DFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); urinary tract recurrence of UC (including all pathological stages and grades); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.
Timepoint [1] 0 0
Randomization up to first occurrence of DFS event (assessed at screening/randomization, every 12 weeks after randomization in first 3 years, every 24 weeks for Years 4 and 5, and at Year 6)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Randomization until death due to any cause (up to approximately 6.5 years)
Secondary outcome [2] 0 0
Disease-Specific Survival (DSS), as Assessed by Investigator - DSS is defined as the time from randomization until the date of death from UC.
Timepoint [2] 0 0
Randomization until death due to UC (up to approximately 6.5 years)
Secondary outcome [3] 0 0
Distant Metastasis-Free Survival (DMFS) - DMFS is defined as the time from randomization to the date of diagnosis of distant (that is, non-locoregional) metastases or death from any cause. Tumor assessment will be performed using radiographic evaluations.
Timepoint [3] 0 0
Randomization up to diagnosis of distant metastases or death from any cause (assessed at screening/randomization, every 12 weeks after randomization in first 3 years, every 24 weeks for Years 4 and 5, and at Year 6)
Secondary outcome [4] 0 0
Non-Urinary Tract Recurrence-Free Survival (NURFS) - NURFS is defined as the time from randomization to the time of first occurrence of a NURFS event. NURFS events include: local (pelvic) recurrence of UC (including soft tissue and regional lymph nodes); distant metastasis of UC; or death from any cause. Tumor assessment will be performed using radiographic evaluations.
Timepoint [4] 0 0
Randomization up to time of first occurrence of a NURFS event (assessed at screening/randomization, every 12 weeks after randomization in first 3 years, every 24 weeks for Years 4 and 5, and at Year 6)
Secondary outcome [5] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [5] 0 0
Screening up to approximately 1 year
Secondary outcome [6] 0 0
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Timepoint [6] 0 0
Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, and every 8 cycles from Cycle 8; at treatment discontinuation (up to 1 year); 90 days after last dose (last dose = up to 1 year) (Cycle length = 21 days)
Secondary outcome [7] 0 0
European Quality of Life (EuroQoL) Group 5-Dimension 5-Level (EQ-5D-5L) Self Report Questionnaire Health Utility Score - Detailed timeframe: Day 1 of Cycles 1, 3, 5, 7, 9, 11, 13, 15, at treatment/observation period discontinuation (up to 1 year), thereafter every 12 weeks up to Year 3 and then every 24 weeks up to Year 5, at Year 6, additionally at 6, 12, 24 weeks after disease recurrence (any time up to 6 years) (Cycle length = 21 days)
Timepoint [7] 0 0
Day 1 of Cycle 1 up to 6 (detailed timeframe is provided in outcome description section)
Secondary outcome [8] 0 0
Minimum Observed Serum Atezolizumab Concentration (Cmin)
Timepoint [8] 0 0
Pre-dose (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, every 8 cycles from Cycle 8, at treatment discontinuation (up to 1 year), 120 days after treatment discontinuation (up to 1 year 4 months)
Secondary outcome [9] 0 0
Maximum Observed Serum Atezolizumab Concentration (Cmax)
Timepoint [9] 0 0
Pre-dose (Hour 0) and 0.5 hours after end of infusion on Day 1 of Cycle 1 (infusion duration = 60 minutes, Cycle length = 21 days)

Eligibility
Key inclusion criteria
- Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma
[TCC]) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)

- Participants who have not received prior platinum-based neoadjuvant chemotherapy, have
refused or are ineligible ("unfit") for cisplatin-based adjuvant chemotherapy

- Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens from surgical
resection (i.e., radical cystectomy, nephroureterectomy, or lymph node dissection) in
paraffin blocks (blocks preferred) or at least 15 unstained slides, with an associated
pathology report, for central testing and determined to be evaluable for tumor PD-L1
expression prior to study enrollment

- Absence of residual disease and absence of metastasis, as confirmed by a negative
baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the
pelvis, abdomen, and chest no more than 4 weeks prior to randomization

- Full recovery from cystectomy or nephroureterectomy within 14 weeks following surgery

- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
(</=) 2

- Life expectancy greater than or equal to (>/=) 12 weeks

- Adequate hematologic and end-organ function

- For women who are not postmenopausal or surgically sterile: agreement to remain
abstinent or use contraceptive methods that result in a failure rate of less than (<)
1 percent (%) per year during the treatment period and for at least 5 months after the
last dose of atezolizumab
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment

- Adjuvant chemotherapy or radiation therapy for UC following surgical resection

- Treatment with any other investigational agent or participation in another clinical
trial with therapeutic intent within 28 days or five half-lives of the drug prior to
enrollment

- Malignancies other than UC within 5 years prior to Cycle 1, Day 1

- Pregnancy or breastfeeding

- Significant cardiovascular disease

- Severe infections within 4 weeks prior to Cycle 1, Day 1

- Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day
1

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
or any component of the atezolizumab formulation

- History of autoimmune disease

- Prior allogeneic stem cell or solid organ transplant

- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan

- Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or
hepatitis C or tuberculosis

- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1

- Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
checkpoint blockade therapies, including anti-CD40, anti-cytotoxic
T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1),
and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Macquarie University Hospital - Macquarie University
Recruitment hospital [2] 0 0
Royal Brisbane & Women's Hosp; Cancer Care Serv - Herston
Recruitment hospital [3] 0 0
Monash Medical Centre; Oncology - East Bentleigh
Recruitment hospital [4] 0 0
Austin and Repatriation Medical Centre; Cancer Services - Melbourne
Recruitment postcode(s) [1] 0 0
2109 - Macquarie University
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
VIC 3165 - East Bentleigh
Recruitment postcode(s) [4] 0 0
3084 - Melbourne
Recruitment outside Australia
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Karsiyaka
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Sihhiye, ANKARA
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Ukraine
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Kharkiv Governorate
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Ukraine
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Dnipropetrovsk
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Ukraine
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Kiev
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Ukraine
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Lviv
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Ukraine
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Zaporozhye
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United Kingdom
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Birmingham
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Bristol
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Glasgow
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London
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Middlesborough
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Oxford
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Preston
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase III, open-label, randomized, multicenter study is to evaluate the efficacy and
safety of adjuvant treatment with atezolizumab compared with observation in participants with
muscle-invasive urothelial carcinoma (UC) who are at high risk for recurrence following
resection. Eligible participants will be randomized by a 1:1 ratio into atezolizumab group or
control group.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: WO29636 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries
Contact person responsible for updating information