Spots Global Cancer Trial Database for Avelumab as Neoadjuvant Therapy in Subjects With Urothelial Muscle Invasive Bladder Cancers (AURA Trial)

Study Description

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.

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.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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