A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 1)
- Registration Number
- NCT02951767
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 119
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 1: Treatment-naive Cisplatin Ineligible Participants Atezolizumab Participants with advanced disease who are treatment-naive for advanced urothelial carcinoma and cisplatin ineligible will receive atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity.
- Primary Outcome Measures
Name Time Method 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 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) 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1 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) 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.
DOR as Assessed by the Investigator According to RECIST v1.1 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) 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.
Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1 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) 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.
Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1 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) 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.
Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1 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) 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.
PFS as Assessed by the Investigator According to RECIST v1.1 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) 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.
Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1 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) 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.
Overall Survival (OS) Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months) OS was defined as the time from start of treatment to the time of death from any cause on study.
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) Percentage of Participants Alive at 1-year 1-year Percentage of Participants Who Died Baseline until death (data cutoff date 04 July 2016, up to maximum length of follow-up of 23.52 months) The percentage of participants who died from any cause was reported.
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) Minimum Serum Concentration (Cmin) of Atezolizumab Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8 (Cycle length = 21 days)
Trial Locations
- Locations (77)
USC Norris Cancer Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente; Oncology Clinical Trials
🇺🇸Vallejo, California, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Massachusetts General Hospital;Oncology
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center, Harvard Medical School; Department of Medicine
🇺🇸Boston, Massachusetts, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Minnesota Oncology Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Pinnacle Oncology Hematology
🇺🇸Scottsdale, Arizona, United States
Arizona Oncology - HOPE Wilmot
🇺🇸Tucson, Arizona, United States
UCLA
🇺🇸Los Angeles, California, United States
The Angeles Clinic and Research Institute - W LA Office
🇺🇸Los Angeles, California, United States
Kaiser Permanente - San Marcos
🇺🇸San Marcos, California, United States
University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Georgetown University Medical Center Lombardi Cancer Center
🇺🇸Washington, District of Columbia, United States
Mayo Clinic Cancer Center
🇺🇸Jacksonville, Florida, United States
Piedmont Cancer Institute, PC
🇺🇸Atlanta, Georgia, United States
University of Chicago; Hematology/Oncology
🇺🇸Chicago, Illinois, United States
Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Indiana University Health; Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Dana Farber Cancer Inst. ; Dept. of Medical Oncology
🇺🇸Boston, Massachusetts, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Mount Sinai School of Medicine - Tisch Cancer Institute
🇺🇸New York, New York, United States
Oncology Hematology Care Inc
🇺🇸Cincinnati, Ohio, United States
Case Western Reserve Univ; Hem/Onc
🇺🇸Cleveland, Ohio, United States
Willamette Valley Cancer Ctr - 520 Country Club
🇺🇸Eugene, Oregon, United States
Kimmel Cancer Center Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
University of Alabama At Birmingham
🇺🇸Birmingham, Alabama, United States
UCSF
🇺🇸San Francisco, California, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Urology Cancer Center & GU Research Network
🇺🇸Omaha, Nebraska, United States
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
🇺🇸Nashville, Tennessee, United States
Ctr for Cancer and Blood Disorders
🇺🇸Fort Worth, Texas, United States
Texas Oncology - Houston (Gessner)
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates - Lake Wright Cancer Center
🇺🇸Norfolk, Virginia, United States
Bcca - Cancer Center Southern Interior
🇨🇦Kelowna, British Columbia, Canada
BCCA-Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, 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
APHP - Hospital Saint Louis
🇫🇷Paris, France
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
Hopital Foch; Oncologie
🇫🇷Suresnes, France
Institut Gustave Roussy; Oncologie Medicale
🇫🇷Villejuif, France
Charité - Universitätsmedizin Berlin; CC 8: Chirurgische Medizin; Klinik für Urologie
🇩🇪Berlin, Germany
Universitätsklinikum Freiburg; Chirurgische Klinik; Abteilung Urologie
🇩🇪Freiburg, Germany
Universitätsklinikum Düsseldorf; Urologische Klinik
🇩🇪Düsseldorf, Germany
Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik
🇩🇪München, Germany
Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II
🇩🇪Hamburg, Germany
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
🇮🇹Milano, Lombardia, Italy
Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia
🇮🇹Arezzo, Toscana, Italy
The Netherlands Cancer Institute - Antoni Van Leeuwenhoekziekenhuis
🇳🇱Amsterdam, Netherlands
Clinica Universitaria de Navarra; Servicio de Oncologia
🇪🇸Pamplona, Navarra, 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
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
🇪🇸Sevilla, Spain
University Hospital Birmingham The Cancer Centre, Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Sarah Cannon Research Institute
🇬🇧London, United Kingdom
Barts and The London
🇬🇧London, United Kingdom
Royal Marsden Hospital; Dept of Medical Oncology
🇬🇧Sutton, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Wirral, United Kingdom
Rocky Mountain Cancer Center - Aurora
🇺🇸Aurora, Colorado, United States
University Of Colorado
🇺🇸Aurora, Colorado, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Yale Cancer Center ; Medical Oncology
🇺🇸New Haven, Connecticut, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States