Atezolizumab Plus One-year BCG Bladder Instillation in BCG-naive High-risk Non-muscle Invasive Bladder Cancer Patients
NCT ID: NCT03799835
Last Updated: 2024-12-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
517 participants
INTERVENTIONAL
2019-01-17
2028-10-31
Brief Summary
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The primary objective is to evaluate the efficacy of atezolizumab as measured by Event-Free survival.
Detailed Description
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* Arm A (control arm): BCG only
* Arm B (experimental arm): BCG+ atezolizumab
The are two factors of stratifications (center and CIS).
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A : control arm
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).
BCG
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®
Arm B: experimental arm
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).
BCG
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®
Atezolizumab
IV perfusion
Interventions
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BCG
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®
Atezolizumab
IV perfusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Adult man and women ( age ≥18 years)
3. 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)
4. Tumor tissue available from the surgery for central confirmation of the diagnosis and analysis the expression of PD-L1
5. 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)
6. 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
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
8. Life expectancy ≥12 weeks
9. 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)
10. 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)
11. 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
12. Patients affiliated to the social security system
13. 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.
Exclusion Criteria
2. 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
3. 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
4. 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.
5. Pregnancy or breastfeeding
6. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
7. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
8. 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.
9. Serum albumin \<2.5 g/dL
10. Known HIV infection
11. 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.
12. Known active tuberculosis
13. 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
14. 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.
15. 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.
16. 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
17. Prior allogeneic stem cell or solid organ transplant
18. 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).
19. 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
20. 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
21. 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
22. 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.
23. Person deprived of their liberty or under protective custody or guardianship
18 Years
ALL
No
Sponsors
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Hoffmann-La Roche
INDUSTRY
UNICANCER
OTHER
Responsible Party
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Principal Investigators
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Morgan Roupret, MD-PHD
Role: PRINCIPAL_INVESTIGATOR
Hôpital Pitié-Salpétrière
Yohann Loriot, MD
Role: PRINCIPAL_INVESTIGATOR
Gustave Roussy, Cancer Campus, Grand Paris
Locations
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Groupe Jolimont - Hôpital de Jolimont
Haine-Saint-Paul, , Belgium
AZ Delta - Campus Rumbeke
Roeselare, , Belgium
Centre Hospitalier Universitaire Angers
Angers, , France
Centre Hospitalier Universitaire Bordeaux
Bordeaux, , France
Hôpital G. Montpied
Clermont-Ferrand, , France
Clinique Claude Bernard
Ermont, , France
CHU Grenoble
Grenoble, , France
Hôpital privé Toulon - Sainte Marguerite
Hyères, , France
Hôpital du Kremlin-Bicêtre
Le Kremlin-Bicêtre, , France
Hôpital Saint Vincent
Lille, , France
Hôpital privé de la Louvière
Lille, , France
Hôpital Saint Philibert
Lomme, , France
Insitut Paoli Calmette
Marseille, , France
Centre Hospitalier Universitaire Marseille
Marseille, , France
Centre Hospitalier Universitaire Nîmes
Nîmes, , France
Hôpital européen Georges Pompidou
Paris, , France
Hôpital Saint Louis
Paris, , France
Groupe Hospitalier Paris Saint Joseph
Paris, , France
Hôpital Cochin
Paris, , France
Institut Mutualiste Montsouris
Paris, , France
Centre Hospitalier Universitaire Tenon
Paris, , France
Hôpital Diaconesses- Croix Saint Simon
Paris, , France
Hôpital La Pitié Salpétrière
Paris, , France
Centre Hospitalier Universitaire Lyon Sud
Pierre-Bénite, , France
Centre CARIO-HPCA
Plérin, , France
Centre Hospitalier Universitaire Rennes
Rennes, , France
Hôpitaux d'instruction des armées Begin
Saint-Mandé, , France
Hôpital Foch
Suresnes, , France
Hôpitaux Leman
Thonon-les-Bains, , France
Institut Claudius Regaud
Toulouse, , France
Centre Hospitalier Universitaire Tours
Tours, , France
Institut Gustave Roussy
Villejuif, , France
Hospital Universitario A Coruña
A Coruña, , Spain
Hospital Universitario de Jerez de la Frontera
Cadiz, , Spain
Hospital Universitario Ramon y Cajal
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Hospital General Universitario Morales Meseguer
Murcia, , Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, , Spain
Countries
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Other Identifiers
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2017-004512-19
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
UC-0160/1717
Identifier Type: -
Identifier Source: org_study_id