ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02792192
Recruitment Status : Recruiting
First Posted : June 7, 2016
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This Phase Ib/II study is designed to assess the safety, tolerability, pharmacokinetics, immunogenicity, patient reported outcomes (PROs), and preliminary anti-tumor activity of atezolizumab administered by intravenous (IV) infusion alone and in combination with intravesical BCG in high-risk NMIBC participants. The study will be conducted in following cohorts: Cohort 1A, Cohort 1B, Cohort 2, and Cohort 3. Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) every 3 weeks (q3w) for a maximum of 96 weeks. BCG will be administered to evaluate dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), or maximum administered dose (MAD). De-escalation will be allowed for up to three dose levels of BCG (full dose [50 mg], 66 percent [%] of a full dose, and 33% of a full dose [Cohort 1B only]). After the MTD or MAD is determined for Cohort 1B, this dose will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3, unless the MTD is determined to be 33% of a full BCG dose. If MTD is determined to be 33% of a full BCG dose, then, no participants will be enrolled into Cohorts 2 and 3 until an assessment of the safety and activity of the combination of atezolizumab plus 33% of a full BCG dose is completed.

Condition or disease Intervention/treatment Phase
Bladder Cancer Drug: Atezolizumab Biological: Bacille Calmette-Guérin Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II, Open-Label Study of the Safety and Pharmacology of Atezolizumab Administered With or Without Bacille Calmette-Guérin in Patients With High-Risk Non−Muscle-Invasive Bladder Cancer
Actual Study Start Date : June 13, 2016
Estimated Primary Completion Date : March 7, 2019
Estimated Study Completion Date : November 27, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: 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.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Other Name: MPDL3280A

Experimental: 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.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Other Name: MPDL3280A

Biological: 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 Name: OncoTICE®

Experimental: 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.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Other Name: MPDL3280A

Biological: 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 Name: OncoTICE®

Experimental: 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.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in respective arm.
Other Name: MPDL3280A

Biological: 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 Name: OncoTICE®




Primary Outcome Measures :
  1. Percentage of Participants With Adverse Events [ Time Frame: From Baseline up to end of study (up to approximately 3.5 years) ]
  2. Cohort 1B: Percentage of Participants With DLTs of BCG [ Time Frame: Days 1-21 ]
  3. Cohort 1B: MTD or MAD of BCG [ Time Frame: Days 1-21 ]
  4. Percentage of Participants With Complete Response (CR) as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 6 [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Percentage of Participants With CR as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 3 [ Time Frame: 3 months ]
  2. Duration of CR, as Assessed on the Basis of Cystoscopy and Urine Cytology [ Time Frame: From first occurence of a documented CR until the time of recurrence of NMIBC or death from any cause (up to approximately 3.5 years) ]
  3. Percentage of Participants With Recurrence-Free Survival (RFS), as Assessed on the Basis of Cystoscopy and Urine Cytology [ Time Frame: 6, 12 and 18 months ]
  4. Bladder-Intact Disease-Free Survival (DFS), as Assessed on the Basis of Cystoscopy and Urine Cytology [ Time Frame: From first study treatment to earliest evidence of progression to muscle-invasive disease in the bladder, regional pelvic progression, distant metastasis, bladder cancer−related death, or cystectomy or death from any cause (up to approximately 3.5 years) ]
  5. Progression-Free Survival (PFS), as Assessed on the Basis of Cystoscopy and Urine Cytology [ Time Frame: Time from first study treatment to the first occurrence of progression to muscle-invasive disease or death from any cause (up to approximately 3.5 years) ]
  6. Cystectomy-Free Survival (CFS), as Assessed on the Basis of Cystoscopy and Urine Cytology [ Time Frame: Time from first study treatment to cystectomy or death from any cause (up to approximately 3.5 years) ]
  7. Overall Survival [ Time Frame: Time from first study treatment to death from any cause (up to approximately 3.5 years) ]
  8. Maximum Observed Serum Concentration of Atezolizumab (Cmax) [ Time Frame: Pre-dose(0 hour [hr])on Day 1 of Cycles 1,2,3,4,8,16,24(Cycle length=21 days),end of atezolizumab treatment(up to 96 weeks),120 days after end of atezolizumab treatment(up to 113 weeks), 0.5 hrs post- infusion (Infusion duration=1 hr) on Day 1 of Cycle 1 ]
  9. Minimum Observed Serum Concentration of Atezolizumab (Cmin) [ Time Frame: Pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, 24 (Cycle length=21 days), end of atezolizumab treatment (up to 96 weeks), 120 days after end of atezolizumab treatment (up to 113 weeks) ]
  10. Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Atezolizumab [ Time Frame: Pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, 24 (Cycle length=21 days), end of atezolizumab treatment (up to 96 weeks), 120 days after end of atezolizumab treatment (up to 113 weeks) ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Histologically confirmed non-muscle-invasive transitional cell carcinoma (TCC) of the bladder with carcinoma in-situ (CIS)
  • 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
  • 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:

  • Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancer
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02792192


Contacts
Contact: Reference Study ID Number: WO29635 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, Alabama
Urology Centers of Alabama Recruiting
Homewood, Alabama, United States, 35209
United States, California
UCLA Urology Clark Clinic Recruiting
Los Angeles, California, United States, 90095
Stanford Univ. Recruiting
Stanford, California, United States, 94305
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
United States, Iowa
University of Iowa Hospitals & Clinics; Urology Recruiting
Iowa City, Iowa, United States, 52242-5002
United States, Maryland
Johns Hopkins Kimmel Cancer Center, Office of Research Administration Recruiting
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, New York
The Montefiore Medical Center & The Albert Einstein College of Medicine; Department of Urology Recruiting
Bronx, New York, United States, 10461
Memorial Sloan Kettering Cancer Center Withdrawn
New York, New York, United States, 10065
United States, North Carolina
Duke University Recruiting
Durham, North Carolina, United States, 27705
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
United States, Oklahoma
Oklahoma University Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
VA Portland Healthcare System Recruiting
Portland, Oregon, United States, 97239
United States, South Carolina
Carolina Urologic Research Center Active, not recruiting
Myrtle Beach, South Carolina, United States, 29572
United States, Wisconsin
Medical College of Wisconsin; Dept Froedtert Clin Can Ctr Terminated
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02792192     History of Changes
Other Study ID Numbers: WO29635
First Posted: June 7, 2016    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

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