Safety and Pharmacology Study of Atezolizumab Alone and in Combination With Bacille Calmette-Guérin (BCG) in High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) Participants
NCT ID: NCT02792192
Last Updated: 2021-10-28
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE1/PHASE2
24 participants
INTERVENTIONAL
2016-06-13
2020-09-29
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)
Participants will receive atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.
Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)
During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Bacille Calmette-Guérin
For Cohort 1B, BCG will be administered (intravesically) at de-escalated doses. De-escalation will be allowed for up to three dose levels of BCG: full dose (50 mg), 66% of full dose, and 33% of full dose. After the MTD or MAD is determined for Cohort 1B, MTD/MAD will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3 (provided MAD or MTD is determined to be either full dose or 66% of a full BCG dose).
Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)
During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Bacille Calmette-Guérin
For Cohort 1B, BCG will be administered (intravesically) at de-escalated doses. De-escalation will be allowed for up to three dose levels of BCG: full dose (50 mg), 66% of full dose, and 33% of full dose. After the MTD or MAD is determined for Cohort 1B, MTD/MAD will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3 (provided MAD or MTD is determined to be either full dose or 66% of a full BCG dose).
Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Bacille Calmette-Guérin
For Cohort 1B, BCG will be administered (intravesically) at de-escalated doses. De-escalation will be allowed for up to three dose levels of BCG: full dose (50 mg), 66% of full dose, and 33% of full dose. After the MTD or MAD is determined for Cohort 1B, MTD/MAD will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3 (provided MAD or MTD is determined to be either full dose or 66% of a full BCG dose).
Interventions
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Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Bacille Calmette-Guérin
For Cohort 1B, BCG will be administered (intravesically) at de-escalated doses. De-escalation will be allowed for up to three dose levels of BCG: full dose (50 mg), 66% of full dose, and 33% of full dose. After the MTD or MAD is determined for Cohort 1B, MTD/MAD will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3 (provided MAD or MTD is determined to be either full dose or 66% of a full BCG dose).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* High-risk NMIBC defined by the following:
BCG-unresponsive NMIBC:
Persistence of high-grade CIS at 6 months following an adequate course of BCG; or Stage/grade progression at 3 months after induction BCG; or Recurrence of high-grade CIS after achieving a disease-free state (i.e., CR) following induction of an adequate course of BCG that occurs less than (\<) 6 months after the last exposure to BCG
BCG-relapsing NMIBC:
Recurrence of high-grade CIS after achieving a disease-free state following induction of an adequate course of BCG that occurs greater than or equal to (\>/=) 6 months after the last exposure to BCG
Very high-risk (VHR) BCG-naïve NMIBC:
VHR NMIBC, defined as having at least 1 of the following: Multiple and/or large (greater than \[\>\] 3 centimeters \[cm\]) T1, (HG/G3) tumors; T1, (HG/G3) tumor with concurrent CIS; T1, G3 with CIS in prostatic urethra; Micropapillary variant of non-muscle invasive urothelial carcinoma
* For BCG-unresponsive and BCG-relapsing NMIBC, participants must have received an adequate course of BCG
* Resection of all pTa/pT1 papillary disease
* No prior radiation to bladder or pelvic region
* Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to (\</=) 2;
* Life expectancy \>/=12 weeks
* Adequate hematologic and end-organ function
* Creatinine clearance \>/=30 milliliters per minute (mL/min) (calculated using the Cockcroft-Gault formula)
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 5 months after the last dose of study drug. Women must refrain from donating eggs during this same period.
* For men receiving BCG: Agreement to remain abstinent (refrain from sexual intercourse) or use a condom
* Tumor tissue biopsy within 60 days prior to study entry or availability of an archival specimen obtained within 60 days of study screening
Exclusion Criteria
* Any malignancy within 5 years prior to Cycle 1, Day 1
* History of autoimmune disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or active pneumonitis
* Signs or symptoms of infection within 2 weeks prior to the first dose of study treatment
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to the first dose of study treatment
* Treatment with any approved anti-cancer therapy within 3 weeks prior to the first dose of study treatment
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to the first dose of study treatment
* Pregnant or lactating women, or women intending to become pregnant during the study
* Prior allogeneic stem cell or solid organ transplantation
* Positive test for human immunodeficiency virus (HIV)
* Active hepatitis B or C and/or tuberculosis
* Severe infections within 28 days prior to the first dose of study treatment
* Significant cardiovascular disease
* Major surgical procedure other than for diagnosis within 4 weeks prior to the first dose of study treatment, or anticipation of need for a major surgical procedure during the course of the study
* Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study
* History of prior significant toxicity or intolerance to BCG requiring discontinuation of treatment
* History of prior systemic BCG infection
* History of immunosuppression, or conditions associated with congenital or acquired immune deficiency
* Concurrent febrile illness, urinary tract infection, or gross hematuria
* Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies
* Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first dose of study treatment
* Treatment with systemic immunosuppressive medications within 2 weeks prior to the first dose of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Trials
Role: STUDY_DIRECTOR
Hoffmann-La Roche
Locations
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Stanford Univ.
Stanford, California, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Johns Hopkins Kimmel Cancer Center, Office of Research Administration
Baltimore, Maryland, United States
The Montefiore Medical Center & The Albert Einstein College of Medicine; Department of Urology
The Bronx, New York, United States
Duke University
Durham, North Carolina, United States
Ohio State University
Columbus, Ohio, United States
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, United States
VA Portland Healthcare System
Portland, Oregon, United States
Countries
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References
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Inman BA, Hahn NM, Stratton K, Kopp R, Sankin A, Skinner E, Pohar K, Gartrell BA, Pham S, Rishipathak D, Mariathasan S, Davarpanah N, Carter C, Steinberg GD. A Phase 1b/2 Study of Atezolizumab with or Without Bacille Calmette-Guerin in Patients with High-risk Non-muscle-invasive Bladder Cancer. Eur Urol Oncol. 2023 Jun;6(3):313-320. doi: 10.1016/j.euo.2023.01.013. Epub 2023 Feb 15.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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WO29635
Identifier Type: -
Identifier Source: org_study_id