Durvalumab (MEDI4736) and TREmelimumab in NEOadjuvant Bladder Cancer Patients (DUTRENEO)

Sponsor
Fundacion CRIS de Investigación para Vencer el Cáncer
Study ID
NCT03472274
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Durvalumab — DRUG
    Durvalumab 1500 mg every 4 weeks x 3 cycles
  • Tremelimumab — DRUG
    Tremelimumab 75 mg every 4 weeks x 3 cycles
  • Cisplatin-based neoadjuvant chemotherapy — DRUG
    Regimen 1: 21-day treatment cycle x 3 cycles. * Gemcitabine 1,000-1,200 mg/m2 intravenously on days 1 and 8 every 21 days. * Cisplatin 70 mg/m2 intravenously on day 1 every 21 days. Regimen 2: ddMVAC 14-day treatment cycle x 4 doses. * Methotrexate 30mg/m2 intravenously on day 1 * Vinblastine 3mg/m2 intravenously on day 2 * Doxorubicin 30mg/m2 intravenously on day 2 * Cisplatin 70mg/m2 intravenously on day 2 Granulocyte colony-stimulating factor (G-CSF) for 7 consecutive days (days 4 through 10). Regimen 3: 21-day treatment cycle x 3 cycle * Gemcitabine 1,000 mg/m2 intravenously on day 1 and 8 * Paclitaxel 80 mg/m2 intravenously on day 1 and 8 * Cisplatin 70mg/m2 intravenously on day 1

Study Details

In the treatment of localized/locally advanced urothelial cancer, there are several questions that have not yet been resolved, such as the limited benefit of cisplatin-based chemotherapy in the adjuvant or neoadjuvant context, the difficulty in establishing which groups actually benefit from either perioperative treatment and what are the molecular markers that could help us predict the response to this treatment to allow a better selection of patients. On the other hand, not all patients are candidates for cisplatin-based chemotherapy and carboplatin is not comparable in activity, so there is an urgent need to find other drugs that may offer a therapeutic opportunity to these patients. In the context of metastatic disease, immunotherapy has been able to modify the natural history of this disease, administered as monotherapy, but the combination with double immune checkpoint inhibitors is also being evaluated with promising results. Even this therapeutic strategy is being advanced to the context of adjuvant and neoadjuvant treatment of urothelial tumors. In this sense, on the one hand, the present study, as a research in the neoadjuvant setting, constitutes the opportunity to define molecular phenotypes in bladder cancer since the design of this study will allow both, to evaluate the efficacy of the drug when the tumor is operable and to carry out an extensive analysis of biomarkers in the tumor tissue of these patients with an in-vivo evaluation of immune-based therapy activity. On the other hand, it allows to evaluate a strategy of double-immune checkpoint inhibitors that has already demonstrated activity in metastatic disease and, taking into account, the modest benefit of standard chemotherapy in the perioperative context: platinum-based neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) Modest increase in overall survival, but only a subset of eligible patients are eligible to receive it. In addition, radical cystectomy alone, in MIBC patients, presents a 5-year relapse rate of 10-50%.

Key Dates

Start date
Oct 25, 2018
Status verified
Apr 2023
Primary completion
Apr 30, 2021
Completion
Apr 12, 2023

Study Design

Enrollment
101 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Cisplatin-based neoadjuvant chemotherapy
    Patients allocated to the control arm will receive any of the following cisplatin based neoadjuvant treatment: Regimen 1: Gemcitabine + Cisplatin Regimen 2: Methotrexate + Vinblastine + Doxorubicin + Cisplatin Regimen 3: Gemcitabine + Paclitaxel + Cisplatin
  • Experimental: Durvalumab plus Tremelimumab
    Patients randomized to experimental arma will receive 28-day treatment cycle x 3 cycles of Durvalumab + Tremelimumab 75 mg every 4 weeks

Primary Outcome Measure

Antitumor activity [ Time Frame: 20 weeks ]

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