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

NCT03799835 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: UC-0160/17172017-004512-19
• Study Type: interventional
• Target: 517
• Locations: 3 countries
• Sites: 38

Brief 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.

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (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.

  5 years

Secondary Outcomes (9)

• High-grade recurrence-free survival

  5 years

• Progression-free survival

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

• Disease-specific survival

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

• Overall Survival

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

• Disease worsening in each arm

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

Study Arms (2)

Arm A : control arm

ACTIVE COMPARATOR

BCG 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).

Drug: BCG

Arm B: experimental arm

EXPERIMENTAL

BCG 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).

Drug: BCG; Drug: Atezolizumab

Interventions

BCG DRUG

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®

Also known as: Bacillus Calmette Guerin (BCG) Medac®, OncoTice

Arm A : control arm; Arm B: experimental arm

Atezolizumab DRUG

IV perfusion

Also known as: MPDL3280A, Tecentriq®

Arm B: experimental arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• UNICANCER: lead
• Hoffmann-La Roche: collaborator

Study Sites (38)

Groupe Jolimont - Hôpital de Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

AZ Delta - Campus Rumbeke

Roeselare, 8800, Belgium

Location

Centre Hospitalier Universitaire Angers

Angers, 49933, France

Location

Centre Hospitalier Universitaire Bordeaux

Bordeaux, 33000, France

Location

Hôpital G. Montpied

Clermont-Ferrand, 63003, France

Location

Clinique Claude Bernard

Ermont, 95120, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

Hôpital privé Toulon - Sainte Marguerite

Hyères, 83400, France

Location

Hôpital du Kremlin-Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

Hôpital Saint Vincent

Lille, 59020, France

Location

Hôpital privé de la Louvière

Lille, 59800, France

Location

Hôpital Saint Philibert

Lomme, 59462, France

Location

Insitut Paoli Calmette

Marseille, 13009, France

Location

Centre Hospitalier Universitaire Marseille

Marseille, 13354, France

Location

Centre Hospitalier Universitaire Nîmes

Nîmes, 30900, France

Location

Hôpital européen Georges Pompidou

Paris, 75010, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Groupe Hospitalier Paris Saint Joseph

Paris, 75014, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Institut Mutualiste Montsouris

Paris, 75014, France

Location

Centre Hospitalier Universitaire Tenon

Paris, 75020, France

Location

Hôpital Diaconesses- Croix Saint Simon

Paris, 75020, France

Location

Hôpital La Pitié Salpétrière

Paris, 75651, France

Location

Centre Hospitalier Universitaire Lyon Sud

Pierre-Bénite, 69130, France

Location

Centre CARIO-HPCA

Plérin, 22198, France

Location

Centre Hospitalier Universitaire Rennes

Rennes, 35033, France

Location

Hôpitaux d'instruction des armées Begin

Saint-Mandé, 94160, France

Location

Hôpital Foch

Suresnes, 92150, France

Location

Hôpitaux Leman

Thonon-les-Bains, 74200, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Centre Hospitalier Universitaire Tours

Tours, 3700, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Hospital Universitario A Coruña

A Coruña, 15006, Spain

Location

Hospital Universitario de Jerez de la Frontera

Cadiz, 11009, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, 38320, Spain

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

BCG Vaccine; atezolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Morgan Roupret, MD-PHD

  Hôpital Pitié-Salpétrière

  PRINCIPAL INVESTIGATOR

• Yohann Loriot, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 10, 2019
• Study Start: January 17, 2019
• Primary Completion: June 1, 2025
• Study Completion (Estimated): October 1, 2028
• Last Updated: December 11, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2); FR (30); ES (6)