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Bladder CancerPhase 3ALBANNCT03799835

Atezolizumab Plus One-year BCG Bladder Instillation in BCG-naive High-risk Non-muscle Invasive Bladder Cancer Patients

A Phase 3 study testing BCG and Atezolizumab in people with Bladder Cancer, run by UNICANCER at 38 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is an open-label, randomized, multicentric study in patients with high-risk non-muscle invasive bladder cancer who had never received BCG for this disease. The primary objective is to evaluate the efficacy of atezolizumab as measured by Event-Free survival. 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?
BCG and Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
517 participants
Where
38 sitesin 3 countries
Study dates
17 Jan 2019to Oct 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

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

  • Signed informed consent form after the last endoscopic surgery (TURBT)
  • Adult man and women ( age ≥18 years)
  • Any high risk non muscle invasive urothelial carcinoma histologically confirmed (mixed histology tumors allowed if urothelial carcinoma histology is predominant) defined on the TURBT as any of the following :
  • T1 tumor and/or
  • High grade (WHO 2004) and/or
  • Grade 3 (WHO1973) and/or
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  • Carcinoma in situ (CIS)
  • Tumor tissue available from the surgery for central confirmation of the diagnosis and analysis the expression of PD-L1
  • At least one additional (second) resection of the primary tumor has been performed in any of the following cases [without upstaging towards Muscle Invasive Bladder Cancer (EAU guidelines, 2017)] :
  • T1 tumors at physician's discretion,
  • incomplete initial TURB,
  • no muscle in the specimen (can be omitted if TaLG/G1 tumors or primary CIS only was found)
  • Absence of metastasis in pelvis, abdomen, or chest, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan no more than 90 days prior to the first study treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
  • Life expectancy ≥12 weeks
  • Systolic blood pressure (BP) <160 mmHg and diastolic BP <95 mmHg, as documented within 7 days prior to the first study treatment (hypertension allowed provided it is controlled)
  • Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 7 days prior to the first study treatment:
  • absolute neutrophil count (ANC) ≥1500 cells/μL
  • white blood cell (WBC) counts >2500/μL
  • Lymphocyte count ≥300/μL
  • Platelet count ≥100,000/μL
  • Hemoglobin ≥9.0 g/dL
  • aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase ≤2.5 × the upper limit of normal (ULN)
  • Serum bilirubin ≤1.0 × ULN Patients with known Gilbert disease who have serum bilirubin level ≤3 × ULN may be enrolled.
  • Partial thromboplastin time (PTT)/Prothrombin Time (PT) ≤1.5 × ULN or international normalized ratio (INR) <1.7 × ULN
  • Calculated creatinine clearance ≥20 mL/min (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 atezolizumab
  • Patients affiliated to the social security system
  • Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Who cannot join

  • Patient having received previous BCG therapy for bladder cancer
  • Any approved anti-cancer therapy, including systemic chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment. Hormone-replacement therapy or oral contraceptives are allowed
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to day 1 of study treatment
  • Malignancies other than urothelial cancer within 5 years prior to Day 1 of cycle 1 of treatment except the following:
  • Patients with localized low risk prostate cancer (defined as Stage ≤T2b, Gleason score ≤7, and PSA at prostate cancer diagnosis ≤20 ng/mL [if measured]) treated with curative intent (radiotherapy and/or prostatectomy) and without prostate-specific antigen (PSA) recurrence are eligible.
  • Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤7 and PSA ≤10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
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  • Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death <5% at 5 years) are eligible provided they meet all of the following criteria: malignancy treated with expected curative intent (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) and no evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers.
  • Pregnancy or breastfeeding
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  • History of autoimmune disease or history of immunosuppression, or conditions associated with congenital or acquired immune deficiency , including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 6 for a more comprehensive list of autoimmune diseases)
  • Patients with a history of autoimmune-related hypothyroidism/hyperthyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
  • Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan may be eligible.
  • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Serum albumin <2.5 g/dL
  • Known HIV infection
  • Patients with active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen (HBsAg) test prior the randomisation) or hepatitis C.
  • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody (HBc Ab) and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomisation.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known active tuberculosis
  • Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Signs or symptoms of urinary infection and/or other signs and symptoms > grade 1 (NCI CTCAE v5.0) within 2 weeks prior to Cycle 1, Day 1
  • Patients receiving therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1 are not eligible
  • Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months before Cycle1, Day 1, unstable arrhythmias, or unstable angina.
  • Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
  • Major surgical procedure other than for diagnosis within 4 weeks prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Prior allogeneic stem cell or solid organ transplant
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation if such a live, attenuated vaccine will be required during the study
  • Influenza vaccination should be given during influenza season only (approximately October through May in the Northern Hemisphere and approximately April through September in the Southern Hemisphere). Patients must agree not to receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1, at randomization, during treatment or within 5 months following the last dose of atezolizumab (for patients randomized to atezolizumab).
  • Any other disease, 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-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons, interleukin 2 (IL-2)) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
  • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea, multiple doses for contrast allergy) may be enrolled in the study.
  • The use of inhaled or low-dose (e.g., ≤10 mg/day prednisone) corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, mineralocorticoids (e.g., fludrocortisone for adrenal insufficiency) and low-dose corticosteroids for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
  • Person deprived of their liberty or under protective custody or guardianship

Trial locations and contacts

38 sites in 3 countries.

38 sites in 3 countries

France30 sites

  • Centre Hospitalier Universitaire Angers

    Angers, 49933

  • Centre Hospitalier Universitaire Bordeaux

    Bordeaux, 33000

  • Hôpital G. Montpied

    Clermont-Ferrand, 63003

  • Clinique Claude Bernard

    Ermont, 95120

  • CHU Grenoble

    Grenoble, 38043

  • Hôpital privé Toulon - Sainte Marguerite

    Hyères, 83400

  • Hôpital du Kremlin-Bicêtre

    Le Kremlin-Bicêtre, 94270

  • Hôpital Saint Vincent

    Lille, 59020

  • Hôpital privé de la Louvière

    Lille, 59800

  • Hôpital Saint Philibert

    Lomme, 59462

  • Insitut Paoli Calmette

    Marseille, 13009

  • Centre Hospitalier Universitaire Marseille

    Marseille, 13354

  • Centre Hospitalier Universitaire Nîmes

    Nîmes, 30900

  • Hôpital européen Georges Pompidou

    Paris, 75010

  • Hôpital Saint Louis

    Paris, 75010

  • Groupe Hospitalier Paris Saint Joseph

    Paris, 75014

  • Hôpital Cochin

    Paris, 75014

  • Institut Mutualiste Montsouris

    Paris, 75014

  • Centre Hospitalier Universitaire Tenon

    Paris, 75020

  • Hôpital Diaconesses- Croix Saint Simon

    Paris, 75020

  • Hôpital La Pitié Salpétrière

    Paris, 75651

  • Centre Hospitalier Universitaire Lyon Sud

    Pierre-Bénite, 69130

  • Centre CARIO-HPCA

    Plérin, 22198

  • Centre Hospitalier Universitaire Rennes

    Rennes, 35033

  • Hôpitaux d'instruction des armées Begin

    Saint-Mandé, 94160

  • Hôpital Foch

    Suresnes, 92150

  • Hôpitaux Leman

    Thonon-les-Bains, 74200

  • Institut Claudius Regaud

    Toulouse, 31059

  • Centre Hospitalier Universitaire Tours

    Tours, 3700

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Spain6 sites

  • Hospital Universitario A Coruña

    A Coruña, 15006

  • Hospital Universitario de Jerez de la Frontera

    Cadiz, 11009

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital General Universitario Morales Meseguer

    Murcia, 30008

  • Hospital Universitario de Canarias

    Santa Cruz de Tenerife, 38320

Other trials in Spain

Belgium2 sites

  • Groupe Jolimont - Hôpital de Jolimont

    Haine-Saint-Paul, 7100

  • AZ Delta - Campus Rumbeke

    Roeselare, 8800

Other trials in Belgium

About this study

Official title: An Open Label, Randomized, Phase III Trial, Evaluating Efficacy of Atezolizumab in Addition to One Year BCG (Bacillus CaLmette-Guerin) Bladder Instillation in BCG-naive Patients With High-risk Non-muscle Invasive Bladder cANcer

This is an open-label, randomized, multicentric study in patients with high-risk non-muscle invasive bladder cancer who had never received BCG for this disease.

The primary objective is to evaluate the efficacy of atezolizumab as measured by Event-Free survival.

Read the detailed description

ALBAN study recruited 517 patients in 45 centers in Europe (France, Belgium and Spain), according to a ratio 1:1 in the following arms of treatment:

  • Arm A (control arm): BCG only
  • Arm B (experimental arm): BCG+ atezolizumab

The are two factors of stratifications (center and CIS).

Conditions
Bladder Cancer
Being tested
BCG, Atezolizumab
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.

  • BCGDrug

    Also called Bacillus Calmette Guerin (BCG) Medac®, OncoTice

    Intravesical administration OncoTice wil be used only under two conditions : BCG Medac® unavailable and the patient has received at minimum one instillation of BCG Medac®

  • AtezolizumabDrug

    Also called MPDL3280A, Tecentriq®

    IV perfusion

Study groups in NCT03799835
Study groupRoleWhat they receive
Arm A : control armActive comparatorBCG therapy only BCG therapy will be administered in two phases: * induction phase: weekly administration of full dose of BCG intravesically up to 6 weeks, starting on the day of the first induction instillation (D1) * maintenance phase: full-dose BCG administered once per week for 3 weeks, at week 13 (i.e. 3 months after the first BCG instillation of induction, D1), at week 26 (6 months from D1) and week 52 (12 months from D1).
Receives: Drug: BCG
Arm B: experimental armExperimentalBCG therapy + administration of atezolizumab 1. BCG therapy will be administered in two phases: * induction phase: weekly administration of full dose of BCG intravesically up to 6 weeks, starting on the day of the first induction instillation (D1) * maintenance phase: full-dose BCG administered once per week for 3 weeks, at week 13 (i.e. 3 months after the first BCG instillation of induction, D1), at week 26 (6 months from D1) and week 52 (12 months from D1). 2. atezolizumab is administered by IV infusion every 3 weeks (21 [± 2] days) for 1 year (18 cycles as a maximum).
Receives: Drug: BCG; Drug: Atezolizumab

What is being measured

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

  1. Event-Free Survival

    The primary efficacy endpoint is event-free survival defined as the time from randomization to the time of first event-free survival (EFS) event restricted to high grade or low grade Ta tumor at any time after the start of therapy; T1 tumor and higher (e.g .T2) at any time after the start of therapy; CIS tumor at least 6 months after the start of therapy ( Persistent CIS without papillary tumor at 3 months without any other event for EFS will not be an event); any UTUC after NMIBC; any N+ at any time after the start of therapy; any M+ at any time after the start of therapy; or death whatever the cause.

    Measured: 5 years

Secondary outcomes (9)

  1. High-grade recurrence-free survival

    High-grade recurrence-free survival is defined by reappearance of high-grade risk disease (high grade, T1 or CIS) or death.

    Measured: 5 years

  2. Progression-free survival

    Progression- free survival defined as the time from randomization to the date of disease progression defined as increase of stage from Ta to T1 or from CIS to T1; progression to Muscle Invasive Bladder Cancer (T≥ 2) or to lymph node N+ or to distant disease M+; the date of progression being determined by the endoscopic resection (TURBT) for a local relapse or by CT scan in case of non-local relapse.

    Measured: From randomization to the date of progression, assessed up to 5 years

  3. Disease-specific survival

    Disease-specific survival defined as the time from randomization to the date of death from bladder cancer.

    Measured: From randomization to the date of death, assessed up to 5 years

  4. Overall Survival

    Overall Survival defined as the time from randomization to the date of death from any cause.

    Measured: From randomization to the date of death, assessed up to 5 years

  5. Disease worsening in each arm

    Disease worsening, defined as cystectomy or change in therapy indicative, including systemic chemotherapy or radiation therapy. The date of diagnosis (cystoscopy or CT scan) leading to cystectomy or chemotherapy will be considered as the time of disease worsening.

    Measured: From randomization to the date of death, assessed up to 5 years

  6. Complete response in each arm

    Complete response is assessed by cystoscopy and cytology.

    Measured: 6 weeks and 2 years after randomization

  7. Complete response among patients with CIS

    Complete response is assessed by cystoscopy and cytology.

    Measured: 6 weeks and 2 years after randomization

  8. National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

    The frequency, nature, and severity of adverse events graded according to NCI CTCAE v5.0 and according to the immune-related adverse event (irAE).

    Measured: Throughout study completion, assessed up to 5 years

  9. Quality of life questionnaire (QLQ): QLQ-C30 questionnaire (EORTC)

    This self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

    The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

    All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Measured: At randomization, every 12 weeks for years 1 and 2 after randomization, then every 24 weeks for years 3 to 5 after randomization

Timeline

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

  1. First posted10 Jan 2019
  2. Study start17 Jan 2019
  3. Primary completionJun 2025 (estimated)
  4. Study completionOct 2028 (estimated)

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
517 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03799835
Sponsor's protocol ID
UC-0160/1717
Other IDs
2017-004512-19, 2017
Acronym
ALBAN
Status last verified
Dec 2024
First submitted
8 Jan 2019
Last updated
11 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BCG and Atezolizumab in people with Bladder Cancer, run by UNICANCER at 38 sites in 3 countries.

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 29 inclusion and 38 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: under way, not looking for participants, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in France, Spain, Belgium. 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Event-Free Survival (time frame: 5 years). 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 NCT03799835.

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 11 Dec 2024.

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