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Bladder CancerPhase 1/2NCT02792192

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

A Phase 1/2 study testing Atezolizumab and Bacille Calmette-Guérin in people with Bladder Cancer, run by Hoffmann-La Roche at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Atezolizumab and Bacille Calmette-Guérin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
8 sitesUnited States
Study dates
13 Jun 2016to 29 Sep 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Johns Hopkins Kimmel Cancer Center, Office of Research Administration

    Baltimore, Maryland, 21205

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Ohio State University

    Columbus, Ohio, 43210

  • Duke University

    Durham, North Carolina, 27705

  • Oklahoma University Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • VA Portland Healthcare System

    Portland, Oregon, 97239

  • Stanford Univ.

    Stanford, California, 94305

  • The Montefiore Medical Center & The Albert Einstein College of Medicine; Department of Urology

    The Bronx, New York, 10461

Other trials in United States

About this study

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

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.

Conditions
Bladder Cancer
Being tested
Atezolizumab, Bacille Calmette-Guérin
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL3280A

    Atezolizumab will be administered as per the schedule specified in respective arm.

  • Bacille Calmette-GuérinBiological

    Also called OncoTICE®

    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).

Study groups in NCT02792192
Study groupRoleWhat they receive
Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)ExperimentalParticipants will receive atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.
Receives: Drug: Atezolizumab
Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)ExperimentalDuring 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.
Receives: Drug: Atezolizumab; Biological: Bacille Calmette-Guérin
Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)ExperimentalDuring 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.
Receives: Drug: Atezolizumab; Biological: Bacille Calmette-Guérin
Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)ExperimentalDuring 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.
Receives: Drug: Atezolizumab; Biological: Bacille Calmette-Guérin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Adverse Events

    Percentage of participants with at least one adverse event during the study.

    Measured: From Baseline up to end of study (up to approximately 4.3 years)

  2. Cohort 1B: Percentage of Participants With DLTs of BCG

    Percentage of participants with dose-limiting toxicities (DLT) of BCG in Cohort 1B.

    Measured: Days 1-21

  3. Cohort 1B: MAD of BCG

    Maximum administered dose (MAD) of BCG.

    Measured: 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

    CR at 6 months after the start of study treatment as assessed by the investigator on the basis of cystoscopic assessment and urine cytology.

    Measured: 6 months

Secondary outcomes (10)

  1. Percentage of Participants With CR as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 3

    CR at the 3-month disease assessment, evaluated by both cystoscopy and cytology.

    Measured: 3 months

  2. Duration of CR, as Assessed on the Basis of Cystoscopy and Urine Cytology

    Duration of CR will be defined for participants with a CR as the time from the first occurrence of a documented complete response to recurrence of high-grade NMIBC or death from any cause.

    Measured: From first occurence of a documented CR until the time of recurrence of NMIBC or death from any cause (up to approximately 4.3 years)

  3. Percentage of Participants With Recurrence-Free Survival (RFS), as Assessed on the Basis of Cystoscopy and Urine Cytology

    RFS rate at 6, 12, and 18 months, defined as the proportion of patients who are alive and free of persistent/recurrent high-grade NMIBC.

    Measured: 6, 12 and 18 months

  4. Bladder-Intact Disease-Free Survival (DFS), as Assessed on the Basis of Cystoscopy and Urine Cytology

    Bladder-intact DFS was defined as the time from the 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.

    Measured: 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 4.3 years)

  5. Progression-Free Survival (PFS), as Assessed on the Basis of Cystoscopy and Urine Cytology

    PFS, defined as the time from the first study treatment to the first occurrence of progression to muscle-invasive disease based on cystoscopy and urine cytology or death from any cause.

    Measured: Time from first study treatment to the first occurrence of progression to muscle-invasive disease or death from any cause (up to approximately 4.3 years)

  6. Cystectomy-Free Survival (CFS), as Assessed on the Basis of Cystoscopy and Urine Cytology

    Cystectomy-free survival, defined as from start of study treatment to bladder removal for any cause or death from any cause.

    Measured: Time from first study treatment to cystectomy or death from any cause (up to approximately 4.3 years)

  7. Overall Survival

    Measured: Time from first study treatment to death from any cause (up to approximately 4.3 years)

  8. Maximum Observed Serum Concentration of Atezolizumab (Cmax)

    Maximum observed serum concentration of Atezolizumab (Cmax)

    Measured: Cycle 1 Day 1 post-dose (Cycle length=21 days)

  9. Minimum Observed Serum Concentration of Atezolizumab (Cmin)

    Minimum observed serum concentration of atezolizumab (Cmin)

    Measured: Pre-dose (0 hr) on Day 1 of Cycles 2, 3, 4 and 8 (Cycle length=21 days)

  10. Percentage of Participants With Anti-Therapeutic Antibody (ADA) Response to Atezolizumab

    Percentage of participants with anti-therapeutic antibody (ADA) response to atezolizumab.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2016 (estimated)
  2. Study start13 Jun 2016
  3. Primary completion29 Sep 2020
  4. Study completion29 Sep 2020

Why it stopped: The study was terminated early as the study had met its goals of providing preliminary safety and efficacy information for atezolizumab monotherapy alone and in combination with BCG in NMIBC.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02792192
Sponsor's protocol ID
WO29635
Status last verified
Sep 2021
First submitted
2 Jun 2016
Last updated
28 Oct 2021
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 36803840

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Atezolizumab and Bacille Calmette-Guérin in people with Bladder Cancer, run by Hoffmann-La Roche at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Adverse Events (time frame: From Baseline up to end of study (up to approximately 4.3 years)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02792192, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2021.

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