Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers (AURA Trial)

NCT03674424 | Completed Phase 2

• 1 other identifier: IJB-AURA-ODN-004
• Study Type: interventional
• Target: 137
• Locations: 2 countries
• Sites: 10

Brief Summary

Open-label, interventional, multi-centre, randomized phase II study. Cancer studied is non-metastatic muscle invasive bladder cancer (MIBC). Avelumab administered every 2 weeks is used as neoadjuvant therapy in subjects with urothelial muscle invasive bladder cancers in combination with standard chemotherapy or alone.

Conditions

Non-metastatic Muscle Invasive Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• To determine the pathologic complete response (ypT0/Tis ypN0) following neoadjuvant treatment in patients with non-metastatic MIBC.

  \- Outcome measure: Pathological complete response is defined as the absence of invasive carcinoma (ypT0/Tis) disease and the absence of microscopic lymph node metastases (ypN0) on the final surgical specimen.

  during surgery

Secondary Outcomes (4)

• To determine the pathologic response rate (<ypT2N0)

  during surgery

• Assessment of the toxicity profile of regimen using the adverse events reported: NCI CTCAE v4.03

  through study completion, an average of 3 months

• Assessment of local or distant recurrence

  at 12 and 36 months after surgery (or at 12 and 36 months after last treatment dose if no surgery was performed)

• Assessment of overall survival

  minimum 36 months FU after surgery (or after last treatment dose if no surgery).

Study Arms (4)

DD-MVAC + avelumab

EXPERIMENTAL

Methotrexate, vinblastine, doxorubicin and cisplatin (DD-MVAC) given in combination with Avelumab. DD-MVAC consists of Methotrexate 30 mg/m2 iv day 1, Vinblastine 3 mg/m2 iv day 2, Cisplatin 70 mg/m2 iv day 2 and Doxorubicin 30 mg/m2 iv day 2. Each cycle is given every 2 weeks for a maximum of 4 administrations Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 2 every 2 weeks. Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy

Drug: Avelumab; Procedure: cystectomy; Combination Product: DD-MVAC

CG+ avelumab

EXPERIMENTAL

Cisplatin, gemcitabine (CG) consists of Gemcitabine 1000 mg/m2 iv in day 1 and day 8 and Cisplatin 70 mg/m2 iv in day 1. Each cycle is given every 3 weeks for a maximum of 4 administrations. Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 1 every 2 weeks Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy

Drug: Avelumab; Procedure: cystectomy; Combination Product: CG

PG+ avelumab

EXPERIMENTAL

Paclitaxel, gemcitabine (PG) consists of Paclitaxel 80 mg/m2 iv in day 1 and day 15 and Gemcitabine 1000 mg/m2 iv in day 1 and day 15. Each cycle is repeated every 3 weeks for a maximum of 4 administrations. Chemotherapy is associated with Avelumab 10 mg/kg, 1-hour intravenous (iv) infusion, given on day 1 every 2 weeks Cystectomy will be performed 3 to 6 weeks after last administration of chemotherapy

Drug: Avelumab; Procedure: cystectomy; Combination Product: PG

Avelumab

EXPERIMENTAL

Avelumab will be administered at a dose of 10 milligram per kilogram (mg/kg) 1-hour intravenous (iv) infusion once every 2 weeks. Dose reductions are not allowed. Avelumab will be given alone for 4 administrations. Cystectomy will be performed 2 weeks after the last administration of avelumab

Drug: Avelumab; Procedure: cystectomy

Interventions

Avelumab DRUG

Chemotherapy with or without avelumab followed by surgery

Avelumab; CG+ avelumab; DD-MVAC + avelumab; PG+ avelumab

cystectomy PROCEDURE

Cystectomy 3 to 6 weeks after last administration of chemotherapy

Avelumab; CG+ avelumab; DD-MVAC + avelumab; PG+ avelumab

CG COMBINATION_PRODUCT

Chemotherapy 4 cycles of 3 weeks

CG+ avelumab

DD-MVAC COMBINATION_PRODUCT

Chemotherapy 4 cycles of 2 weeks

DD-MVAC + avelumab

PG COMBINATION_PRODUCT

Chemotherapy 2 cycles of 4 weeks

PG+ avelumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• Must have histologically confirmed muscle invasive urothelial carcinoma (transitional cell carcinoma) or urothelial carcinoma with mixed histology of the bladder, renal pelvis or ureters. Stage permitted: T2, T3 or T4a. T stage is based on the standard of care transurethral resection of the bladder tumour (TURBT) sample
• Patients may have nodal disease (Nx, N0, N1 or N2) at imagery but there must be no evidence of distant metastases (M0)
• Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG).
• Be a medically appropriate candidate for surgery as determined by an attending urologist
• Adequate bone marrow function as defined below:
• Absolute neutrophil count ≥1500/µL or 1.5x109/L
• Hemoglobin ≥ 9 g/dL
• Platelets ≥100000/µL or 100x109/L 7)
• Adequate liver function as defined below:
• Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome \< 3xUNL is allowed
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN
• Serum pregnancy test (for subjects of childbearing potential) negative within 7 days prior to study treatment administration.
• Women of childbearing potential must agree to use one highly effective method of contraception prior study entry, during the course of the study and up to 6 months after the last administration of study treatment. Men with childbearing potential partner must agree to use condom during the course of this study and up to 6 months after the last administration of the study treatment.
• Completion of all necessary screening procedures within 28 days prior to treatment.

You may not qualify if:

• Subjects meeting one of the following criteria are not eligible for this study:
• Metastatic disease (M1)
• Has had prior systemic chemotherapy, targeted small molecule therapy, or radiation therapy for urothelial carcinoma
• Prior treatment with drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Has an active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Has had a prior organ transplantation including allogenic stem-cell transplantation.
• Has an active infection requiring systemic therapy
• Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome.
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA is detected)
• Has received vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines such as influenza vaccine.
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 28 days prior to study registration
• History of prior invasive malignancy within 2 years (exception of adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal carcinoma in situ)
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrolment), myocardial infarction (\< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication."

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (10)

UZAntwerpen

Edegem, Antwerpen, 2650, Belgium

Location

Centre Hospitalier Universitaire et Psychiatrique de Mons-Borinage

Mons, Hainaut, 7000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Grand Hôpital de Charleroi

Gilly, 6000, Belgium

Location

CHU de Liège Sart Tilman

Liège, 4000, Belgium

Location

CHU Namur - Sainte Elisabeth

Namur, 5000, Belgium

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Groupe Hospitalier Paris Saint Joseph

Paris, 75014, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

Hôpitaux universitaires de Strasbourg

Strasbourg, 67091, France

Location

Related Publications (2)

• Blanc J, Carnot A, Barthelemy P, Casert V, Sautois B, Van den Brande J, Vanhaudenarde V, Staudacher L, Seront E, Debien V, Ameye L, Kotecki N, Rothe F, Rorive S, Fantoni JC, Tricard T, Roumeguere T, Awada A, Martinez Chanza N. Avelumab-based neoadjuvant therapy in patients with muscle-invasive bladder cancer (AURA Oncodistinct-004): a phase 2 multicenter clinical trial. J Immunother Cancer. 2025 May 24;13(5):e012045. doi: 10.1136/jitc-2025-012045.

  PMID: 40413024 DERIVED

• Martinez Chanza N, Soukane L, Barthelemy P, Carnot A, Gil T, Casert V, Vanhaudenarde V, Sautois B, Staudacher L, Van den Brande J, Culine S, Seront E, Gizzi M, Albisinni S, Tricard T, Fantoni JC, Paesmans M, Caparica R, Roumeguere T, Awada A. Avelumab as neoadjuvant therapy in patients with urothelial non-metastatic muscle invasive bladder cancer: a multicenter, randomized, non-comparative, phase II study (Oncodistinct 004 - AURA trial). BMC Cancer. 2021 Dec 2;21(1):1292. doi: 10.1186/s12885-021-08990-3.

  PMID: 34856936 DERIVED

MeSH Terms

Interventions

avelumab; Cystectomy

Intervention Hierarchy (Ancestors)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, randomized study. 2 cohorts possible depending on cisplatin-eligibility. Afterwards randomization between 2 arms into the cohort.

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 17, 2018
• Study Start: June 1, 2018
• Primary Completion: December 7, 2021
• Study Completion: January 30, 2025
• Last Updated: February 26, 2025

Record last verified: 2025-01

Locations

BE (6); FR (4)