A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 1)

Bladder Cancer Clinical Trial

Official title:

A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02951767
• Other study ID #: GO29293 (Cohort 1)
• Secondary ID: IMvigor 2102013-
• Status: Completed
• Phase: Phase 2
• Start date: May 31, 2014
• Est. completion date: February 28, 2023

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase II, single-arm study is designed to evaluate the effect of atezolizumab treatment in participants with locally advanced or metastatic urothelial bladder cancer. Participants will be enrolled into 1 of 2 cohorts. Cohort 1 (reported here) will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. Cohort 2 will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. The results of the second cohort are reported separately (NCT02108652). Participants in both cohorts will be given a 1200 milligrams (mg) intravenous (IV) dose of atezolizumab on Day 1 of 21-day cycles. Treatment of participants in Cohort 1 will continue until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or unmanageable toxicity. Treatment of participants in Cohort 2 will continue until loss of clinical benefit or unmanageable toxicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: February 28, 2023
• Est. primary completion date: July 4, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
• Representative tumor specimens as specified by the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than or equal to (>=) 12 weeks
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end organ function Cohort 1-Specific Inclusion Criteria
• No prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma
• Ineligible for cisplatin-based chemotherapy due to one of the following: Impaired renal function, a hearing loss of 25 decibels (dB) at two contiguous frequencies, Grade 2 or greater peripheral neuropathy, or ECOG performance score of 2

Exclusion Criteria:

• Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• Leptomeningeal disease
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled hypercalcemia (greater than [>] 1.5 millimoles per liter [mmol/L] ionized calcium or Ca > 12 milligrams per deciliter [mg/dL] or corrected serum calcium > upper limits of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• Malignancies other than urothelial bladder cancer within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome or incidental prostate cancer
• Pregnant and lactating women
• History of autoimmune disease
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Serum albumin less than (<) 2.5 grams per deciliter (g/dL)
• Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis
• Severe infections within 4 weeks prior to Cycle 1, Day 1
• Significant cardiovascular disease
• Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1
• Prior allogeneic stem cell or solid organ transplant
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Atezolizumab
Atezolizumab 1200 mg will be given by IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.

Locations

Country	Name	City	State
Canada	Bcca - Cancer Center Southern Interior	Kelowna	British Columbia
Canada	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec
Canada	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario
Canada	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario
Canada	Sunnybrook Odette Cancer Centre	Toronto	Ontario
Canada	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario
Canada	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia
France	APHP - Hospital Saint Louis	Paris
France	Hopital Foch; Oncologie	Suresnes
France	Institut Gustave Roussy; Oncologie Medicale	Villejuif
Germany	Charité - Universitätsmedizin Berlin; CC 8: Chirurgische Medizin; Klinik für Urologie	Berlin
Germany	Universitätsklinikum Düsseldorf; Urologische Klinik	Düsseldorf
Germany	Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie	Freiburg
Germany	Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II	Hamburg
Germany	Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik	München
Italy	Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia	Arezzo	Toscana
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia
Netherlands	The Netherlands Cancer Institute - Antoni Van Leeuwenhoekziekenhuis	Amsterdam
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
United Kingdom	University Hospital Birmingham The Cancer Centre, Queen Elizabeth Hospital	Birmingham
United Kingdom	Barts and The London	London
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	Royal Marsden Hospital; Dept of Medical Oncology	Sutton
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Wirral
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Piedmont Cancer Institute, PC	Atlanta	Georgia
United States	Rocky Mountain Cancer Center - Aurora	Aurora	Colorado
United States	University Of Colorado	Aurora	Colorado
United States	University of Alabama At Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center, Harvard Medical School; Department of Medicine	Boston	Massachusetts
United States	Dana Farber Cancer Inst. ; Dept. of Medical Oncology	Boston	Massachusetts
United States	Massachusetts General Hospital;Oncology	Boston	Massachusetts
United States	University of Chicago; Hematology/Oncology	Chicago	Illinois
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	Case Western Reserve Univ; Hem/Onc	Cleveland	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Willamette Valley Cancer Ctr - 520 Country Club	Eugene	Oregon
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Ctr for Cancer and Blood Disorders	Fort Worth	Texas
United States	Indiana University Health; Goshen Center for Cancer Care	Goshen	Indiana
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Houston Methodist Hospital	Houston	Texas
United States	Texas Oncology - Houston (Gessner)	Houston	Texas
United States	Mayo Clinic Cancer Center	Jacksonville	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	The Angeles Clinic and Research Institute - W LA Office	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	USC Norris Cancer Center	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Minnesota Oncology Minneapolis	Minneapolis	Minnesota
United States	Sarah Cannon Cancer Center - Tennessee Oncology, Pllc	Nashville	Tennessee
United States	Yale Cancer Center ; Medical Oncology	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine - Tisch Cancer Institute	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Virginia Oncology Associates - Lake Wright Cancer Center	Norfolk	Virginia
United States	Urology Cancer Center & GU Research Network	Omaha	Nebraska
United States	Kimmel Cancer Center Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF	San Francisco	California
United States	Kaiser Permanente - San Marcos	San Marcos	California
United States	Pinnacle Oncology Hematology	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Stanford Cancer Center	Stanford	California
United States	Arizona Oncology - HOPE Wilmot	Tucson	Arizona
United States	Kaiser Permanente; Oncology Clinical Trials	Vallejo	California
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed by the Independent Review Facility (IRF) According to RECIST v1.1	Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as greater than or equal to (=) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed =4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1	DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed =4 weeks after the initial assessment of CR or PR.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	DOR as Assessed by the Investigator According to RECIST v1.1	DOR was defined as the time from the initial occurrence of documented CR or PR (whichever occurred first) until documented disease progression or death due to any cause on study, whichever occurred first. Tumor response was assessed by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and no new measurable or unmeasurable lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in sum of LD of target lesions in reference to Baseline sum LD.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1	Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as =20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1	PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as =20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1	Tumor response was assessed by the investigator according to RECIST v1.1. Disease progression or PD was defined as =20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The percentage of participants who died or experienced PD was reported.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	PFS as Assessed by the Investigator According to RECIST v1.1	PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the investigator according to RECIST v1.1. Disease progression or PD was defined as =20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1	Tumor response was assessed by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as =30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed =4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% CI was calculated using the Clopper-Pearson method.	Baseline until confirmed disease progression or death, whichever occurred first (assessed at every 9 weeks for the first 12 months, thereafter every 12 weeks until data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	Percentage of Participants Who Died	The percentage of participants who died from any cause was reported.	Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	Overall Survival (OS)	OS was defined as the time from start of treatment to the time of death from any cause on study.	Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)
Secondary	Percentage of Participants Alive at 1-year		1-year
Secondary	Maximum Serum Concentration (Cmax) of Atezolizumab		Pre-dose (0 hours) and 30 minutes post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)
Secondary	Minimum Serum Concentration (Cmin) of Atezolizumab		Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8 (Cycle length = 21 days)
Secondary	Percentage of Participants Positive for Anti-therapeutic Antibodies (ATA) to Atezolizumab		Day 1 of all cycles (Cycle length = 21 days) and at treatment discontinuation (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months)