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A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02108652
First received: April 7, 2014
Last updated: November 3, 2016
Last verified: November 2016
  Purpose
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 will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. The results of Cohort 1 are reported separately (NCT02951767). Cohort 2 (reported here) will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. 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.

Condition Intervention Phase
Bladder Cancer
Drug: Atezolizumab
Phase 2

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Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 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.

  • Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According Modified RECIST [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 months) ]
    Tumor response was assessed by the investigator according to modified RECIST. 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. 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.


Secondary Outcome Measures:
  • Duration of Response as Assessed by the IRF According to RECIST v1.1 [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 months) ]
    Duration of response 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. Disease progression or progressive disease (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. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.

  • Duration of Response as Assessed by the Investigator According to RECIST v1.1 [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 months) ]
    Duration of response 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 (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. 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. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.

  • Duration of Response as Assessed by the Investigator According to Modified RECIST [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 months) ]
    Duration of response 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 modified RECIST. 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. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR.

  • Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1 [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 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. The percentage of participants who died or experienced PD was reported.

  • Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1 [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 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 [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 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 [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 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 Death or Disease Progression as Assessed by the Investigator According to Modified RECIST [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 months) ]
    Tumor response was assessed by the investigator according to modified RECIST. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. 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 Modified RECIST [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 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 modified RECIST. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD. 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 [ Time Frame: Baseline, every 9 weeks for the first 12 months, thereafter every 12 weeks until confirmed disease progression or death, whichever occurred first (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 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.

  • Percentage of Participants Who Died [ Time Frame: Baseline until death (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 months) ]
    The percentage of participants who died from any cause was reported.

  • Overall Survival (OS) [ Time Frame: Baseline until death (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 months) ]
    OS was defined as the time from start of treatment to the time of death from any cause on study.

  • Percentage of Participants Alive at 1-year [ Time Frame: 1-year ]
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: 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 [ Time Frame: Pre-dose (0 hours) on Day 1 of Cycles 1, 2, 3, 4, 8 (Cycle length = 21 days) ]
  • Percentage of Participants Positive for Anti-therapeutic Antibodies (ATA) to Atezolizumab [ Time Frame: Day 1 of all cycles (Cycle length = 21 days) and at treatment discontinuation (data cutoff date 14 September 2015, up to maximum length of follow-up of 15.24 months) ]

Enrollment: 310
Study Start Date: May 2014
Estimated Study Completion Date: August 2017
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 2: Participants With Second-line or Beyond Treatments
Participants with advanced disease who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting will receive atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity.
Drug: Atezolizumab
Atezolizumab 1200 mg given by IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria/loss of clinical benefit or unmanageable toxicity.
Other Names:
  • MPDL3280A
  • Tecentriq

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 2-Specific Inclusion Criteria

  • Disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence.
  • A regimen was defined as participants receiving at least two cycles of a platinum-containing regimen. Participants who had received one cycle of a platinum-containing regimen but discontinued due to Grade 4 hematologic toxicity or Grade 3 or 4 non-hematologic toxicity could also be eligible.
  • Participants who received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing adjuvant/neoadjuvant regimen were considered as second-line participants.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02108652

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35294
United States, Arizona
Scottsdale, Arizona, United States, 85258
Tucson, Arizona, United States, 85710
United States, California
Los Angeles, California, United States, 90024
Los Angeles, California, United States, 90025
Los Angeles, California, United States, 90033
San Francisco, California, United States, 94143-0106
San Marcos, California, United States, 92069
Stanford, California, United States, 94305-5820
Vallejo, California, United States, 94589
United States, Colorado
Aurora, Colorado, United States, 80012
Aurora, Colorado, United States, 80045
United States, Connecticut
Farmington, Connecticut, United States, 06030
New Haven, Connecticut, United States, 06520
United States, District of Columbia
Washington, District of Columbia, United States, 20057
United States, Florida
Jacksonville, Florida, United States, 32224
United States, Georgia
Atlanta, Georgia, United States, 30318
United States, Illinois
Chicago, Illinois, United States, 60637
Harvey, Illinois, United States, 60426
United States, Indiana
Goshen, Indiana, United States, 46526
United States, Kentucky
Louisville, Kentucky, United States, 40402
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02115
Boston, Massachusetts, United States, 02215
United States, Michigan
Ann Arbor, Michigan, United States, 48109
Detroit, Michigan, United States, 48201
United States, Minnesota
Minneapolis, Minnesota, United States, 55404
Rochester, Minnesota, United States, 55905
United States, Nebraska
Omaha, Nebraska, United States, 68130
United States, Nevada
Las Vegas, Nevada, United States, 89148
United States, New York
Abany, New York, United States, 12208
New York, New York, United States, 10016
New York, New York, United States, 10029
New York, New York, United States, 10065
United States, Ohio
Cincinnati, Ohio, United States, 45242
Cleveland, Ohio, United States, 44106
Cleveland, Ohio, United States, 44195
United States, Oregon
Eugene, Oregon, United States, 97401-8122
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Fort Worth, Texas, United States, 76104
Houston, Texas, United States, 77024
Houston, Texas, United States, 77030
San Antonio, Texas, United States, 78229
United States, Virginia
Fairfax, Virginia, United States, 22031
Norfolk, Virginia, United States, 23502
United States, Washington
Seattle, Washington, United States, 98109
Canada, British Columbia
Kelowna, British Columbia, Canada, V1Y 5L3
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Oshawa, Ontario, Canada, L1G 2B9
Ottawa, Ontario, Canada, K1H 8L6
Toronto, Ontario, Canada, M4N 3M5
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
France
Paris, France, 75475
Suresnes, France, 92151
Villejuif, France, 94800
Germany
Berlin, Germany, 12200
Düsseldorf, Germany, 40225
Freiburg, Germany, 79106
Hamburg, Germany, 20246
München, Germany, 81675
Italy
Milano, Lombardia, Italy, 20133
Arezzo, Toscana, Italy, 52100
Netherlands
Amsterdam, Netherlands, 1066 CX
Spain
Pamplona, Navarra, Spain, 31008
Barcelona, Spain, 08035
Barcelona, Spain, 08908
Madrid, Spain, 28007
Madrid, Spain, 28034
Madrid, Spain, 28041
Sevilla, Spain, 41013
United Kingdom
Birmingham, United Kingdom, B15 2TH
London, United Kingdom, E1 2AD
London, United Kingdom, W1G 6AD
Sutton, United Kingdom, SM2 5PT
Wirral, United Kingdom, L63 4JY
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02108652     History of Changes
Other Study ID Numbers: GO29293 (Cohort 2)  IMvigor 210  2013-005486-39 
Study First Received: April 7, 2014
Results First Received: July 1, 2016
Last Updated: November 3, 2016

Keywords provided by Hoffmann-La Roche:
anti-PD-L1
PD-L1
MPDL3280A
PD-1
bladder cancer
atezolizumab
Tecentriq

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 27, 2017