AzTrials
AzTrials

Non-metastatic Muscle Invasive Bladder CancerPhase 2AURANCT03674424

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

A Phase 2 study testing Avelumab, cystectomy and CG in people with Non-metastatic Muscle Invasive Bladder Cancer, run by Jules Bordet Institute at 10 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Avelumab, cystectomy and CG
Could I receive a placebo?
No, everyone receives an active treatment
How many people
137 participants
Where
10 sitesin 2 countries
Study dates
1 Jun 2018to 30 Jan 2025
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Patients must be affiliated to a social security system

Who cannot join

  • 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.
Show all 20Show fewer
  • 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."
  • Pregnant and/or lactating women.
  • Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade >1); however, alopecia, sensory neuropathy Grade ≤2, or other Grade ≤2 not constituting a safety risk based on investigator's judgment are acceptable.
  • Other severe acute chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with the study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Vulnerable persons according to the article L.1121-6 of the CSP, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the CSP.

Trial locations and contacts

10 sites in 2 countries.

10 sites in 2 countries

Belgium6 sites

  • Institut Jules Bordet

    Brussels, 1000

  • UZAntwerpen

    Edegem, Antwerpen, 2650

  • Grand Hôpital de Charleroi

    Gilly, 6000

  • CHU de Liège Sart Tilman

    Liège, 4000

  • Centre Hospitalier Universitaire et Psychiatrique de Mons-Borinage

    Mons, Hainaut, 7000

  • CHU Namur - Sainte Elisabeth

    Namur, 5000

Other trials in Belgium

France4 sites

  • Centre Oscar Lambret

    Lille, 59000

  • Groupe Hospitalier Paris Saint Joseph

    Paris, 75014

  • Hôpital Saint Louis

    Paris, 75475

  • Hôpitaux universitaires de Strasbourg

    Strasbourg, 67091

Other trials in France

About this study

Official title: Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers

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.

Read the detailed description

Open-label, interventional, multi-centre, randomized phase II study. Cancer studied is non-metastatic muscle invasive bladder cancer (MIBC) Patients (male or female) will receive avelumab every 2 weeks in combination with standard chemotherapy or alone. There are 2 cohorts of patients.

Cohort with patients cisplatin-ineligible will receive either avelumab alone or in combination with paclitaxel-gemcitabine chemotherapy.

Cohort with patients cisplatin-eligible will receive either methotrexate, vinblastine, doxorubicine and cisplatin in combination with avelumab or cisplatin, gemcitabine in combination with avelumab.

The estimated number of subjects to screen is 183 patients for an estimated number of 166 patients enrolled for 150 evaluable patients:

26 patients in the paclitaxel, gemcitabine in combination with avelumab arm (cisplatin-ineligible patients) 26 patients in avelumab alone arm (cisplatin-ineligible patients) 49 patients in cisplatin gemcitabine + avelumab arm (cisplatin-eligible patients) 49 patients in methotrexate, vinblastine, doxorubicine and cisplatin + avelumab arm (cisplatin-eligible patients)

AVELUMAB:

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.

Depending on the treatment arm, Avelumab will be given associated with chemotherapy or alone for a maximum of 4 administrations.

DD-MVAC:

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. Pegfilgrastim 6 mg subcutaneous (SQ) 24-48 hours after completion of chemotherapy will be given.

Chemotherapy is associated with Avelumab 10 mg/kg iv given on day 2 every 2 weeks.

CG:

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. Pegfilgrastim 6 mg subcutaneous (SQ) 24-48 hours after completion of chemotherapy will be given.

Chemotherapy is associated with Avelumab 10 mg/kg iv given on day 1 every 2 weeks.

PG:

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 4 weeks for a maximum of 4 administrations.

Chemotherapy is associated with Avelumab 10 mg/kg i.v. given every on day 1 every 2 weeks.

For patients receiving neoadjuvant chemotherapy treatment, the surgery (cystectomy or nephroureterectomy associated to lymphadenectomy) will be performed within 3-6 weeks after the last administration of neoadjuvant chemotherapy treatment.

For patients receiving avelumab alone, the surgery will be performed 2 weeks (+7 days) after the last administration of avelumab.

Any delay in surgery (> 6 weeks after the last chemotherapy administration or >3 weeks after the last administration of avelumab alone) for any reason, needs to be discussed with the PI/Sponsor.

For all patients, neoadjuvant treatment will be stopped if there is evidence of progression of disease (by RECIST 1.1 or investigator's decision) or unacceptable toxicity according to the investigator. In this situation, the investigator will decide if it is needed to proceed directly with the surgery.

The end of study will be declared when all the following criteria will have been met:

  • The study ends after last visit of the last patient remaining in the study.
  • The trial is mature for the analysis of the endpoints as defined in the protocol, if the trial reaches its endpoints.
  • The database has been fully cleaned and frozen for all analyses.
Being tested
Avelumab, cystectomy, CG, DD-MVAC, PG

What participants receive

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

  • AvelumabDrug

    Chemotherapy with or without avelumab followed by surgery

  • cystectomyProcedure or surgery

    Cystectomy 3 to 6 weeks after last administration of chemotherapy

  • CGCombination product

    Chemotherapy 4 cycles of 3 weeks

  • DD-MVACCombination product

    Chemotherapy 4 cycles of 2 weeks

  • PGCombination product

    Chemotherapy 2 cycles of 4 weeks

Study groups in NCT03674424
Study groupRoleWhat they receive
DD-MVAC + avelumabExperimentalMethotrexate, 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
Receives: Drug: Avelumab; Procedure: cystectomy; Combination Product: DD-MVAC
CG+ avelumabExperimentalCisplatin, 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
Receives: Drug: Avelumab; Procedure: cystectomy; Combination Product: CG
PG+ avelumabExperimentalPaclitaxel, 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
Receives: Drug: Avelumab; Procedure: cystectomy; Combination Product: PG
AvelumabExperimentalAvelumab 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
Receives: Drug: Avelumab; Procedure: cystectomy

What is being measured

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

  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.

    Measured: during surgery

Secondary outcomes (4)

  1. To determine the pathologic response rate (<ypT2N0)

    Outcome measure: Pathologic response is defined as the absence of muscle invasive carcinoma (<ypT2N0 disease) on the final surgical specimen.

    Measured: during surgery

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

    Outcome measure: adverse events reported during the study according to NCI CTCAE v4.03

    Measured: through study completion, an average of 3 months

  3. Assessment of local or distant recurrence

    Outcome measure: invasive disease-free survival (iDFS) rate. iDFS period is defined as a time between the surgery (or last treatment dose if no surgery) and the date of diagnosis of local or distant recurrence, or secondary primary malignancy

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

  4. Assessment of overall survival

    overall survival (OS) rate. Overall survival is defined as a time between the surgery (or last treatment dose if no surgery) and the day of death (due to any causes) or day of last news

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

Timeline

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

  1. First posted17 Sep 2018
  2. Study start1 Jun 2018
  3. Primary completion7 Dec 2021
  4. Study completion30 Jan 2025

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open-label, randomized study. 2 cohorts possible depending on cisplatin-eligibility. Afterwards randomization between 2 arms into the cohort.
Masking
None (open label)
Enrolment
137 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03674424
Sponsor's protocol ID
IJB-AURA-ODN-004
Acronym
AURA
Status last verified
Jan 2025
First submitted
12 Sep 2018
Last updated
26 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 40413024

  • 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.

    PubMed 34856936

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avelumab, cystectomy and CG in people with Non-metastatic Muscle Invasive Bladder Cancer, run by Jules Bordet Institute at 10 sites in 2 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 1 inclusion and 20 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: finished, as of the sponsor's last update on 26 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Belgium, France. 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

To determine the pathologic complete response (ypT0/Tis ypN0) following neoadjuvant treatment in patients with non-metastatic MIBC. (time frame: during surgery). 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 NCT03674424, which also lists 2 linked publications.

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 26 Feb 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in