AzTrials
AzTrials

Bladder CancerPhase 2DUTRENEONCT03472274

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

A Phase 2 study testing Durvalumab, Tremelimumab and Cisplatin-based neoadjuvant chemotherapy in people with Bladder Cancer, run by Fundacion CRIS de Investigación para Vencer el Cáncer at 11 sites in Spain.

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

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Durvalumab, Tremelimumab and Cisplatin-based neoadjuvant chemotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
11 sitesSpain
Study dates
25 Oct 2018to 12 Apr 2023
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

  • Male and female subjects; age ≥ 18 years at the time of study entry.
  • Subjects must provide written informed consent prior to performance of any protocol-related procedures, including screening evaluations and must be willing to comply with treatment and follow up.
  • Subjects must have histologic documentation of transitional cell carcinoma of the urothelium (including the urinary bladder, ureter, urethra and renal pelvis) of the urinary tract (cystoscopy and biopsy or positive cytology).
  • Patients must have confirmed cT2-T4 N0-1 M0 (TNM classification).
  • Archival tumour samples for biomarker research in formalin-fixed and paraffin-embedded blocks.
  • Body weight >30kg
Show all 21Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Life expectancy of at least 12 weeks
  • Adequate organ function as determined by:
  • Hematological (without growth factor or transfusion support within 28 days prior to first dose of investigational product)
  • Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L).
  • Platelets ≥ 100,000/mm3 (≥ 100 GI/L)
  • Hemoglobin ≥ 9 g/dL (≥ 90 g/L)
  • Hepatic:
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN.
  • Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's disease ≤ 3 mg/dL (≤ 51.3 μmol/L).
  • Renal:
  • Calculated CrCl or 24-hour urine CrCl>40 mL/min or Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
  • Fasting serum triglycerides ≤ 2.5 × upper limit of normal AND total cholesterol ≤ 300 mg/dL (≤ 7.75 mmol/L). Lipid-lowering medication is allowed.
  • HbA1c ≤ 8%.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.

Who cannot join

  • Histology of pure adenocarcinoma, pure squamous cell carcinoma, or predominant small cell carcinoma or sarcomatoid features in the tumor sample.
  • Evidence of any metastatic lesion outside the primary tumour site identified in the radiological evaluation.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent.
  • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
Show all 35Show fewer
  • Previous therapy with PD-1, PD-L1 or CTLA-4 inhibitors, including durvalumab and tremelimumab.
  • Any concurrent chemotherapy, immunotherapy (IMT), or biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
  • History of severe allergic reactions (ie, Grade 4 allergy, anaphylactic reaction from which the subject did not recover within 6 hours of institution of supportive care) to any unknown allergens or any components of the study drug formulations.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • Major surgery within 4 weeks of study randomization.
  • Prior high-dose chemotherapy requiring hematopoietic stem cell rescue.
  • Prior radiation therapy to >25% of the bone marrow.
  • Current treatment on another clinical trial.
  • Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
  • Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus.
  • Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 electrocardiograms (ECGs).
  • Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
  • Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy)
  • Current treatment with therapeutic doses of Coumadin (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
  • History of active primary immunodeficiency
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive hepatitis B virus (HBV) surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV Ribonucleic acid (RNA).
  • Known positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or C or active hepatitis A.
  • Receipt of live, attenuated vaccine within 30 days prior to the first dose of investigational products.
  • Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to randomization.
  • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
  • History of leptomeningeal carcinomatosis

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Spain11 sites

  • ICO Badalona

    Badalona

  • Hospital Clinic

    Barcelona

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • ICO L'Hospitalet

    L'Hospitalet de Llobregat

  • Hospital 12 de Octubre

    Madrid

  • Hospital Clinico San Carlos

    Madrid

  • Hospital Ramon y Cajal

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • MD Anderson Cancer Center

    Madrid

  • Hospital Marqués de Valdecilla

    Santander

  • Instituto Valenciano de Oncología

    Valencia

Other trials in Spain

About this study

Official title: The DUTRENEO Trial: A Prospective Study to Individualize the Approach With DUrvalumab (MEDI4736) and TREmelimumab in NEOadjuvant Bladder Cancer Patients.

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%.

Conditions
Bladder Cancer
Being tested
Durvalumab, Tremelimumab, Cisplatin-based neoadjuvant chemotherapy
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

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

  • DurvalumabDrug

    Durvalumab 1500 mg every 4 weeks x 3 cycles

  • TremelimumabDrug

    Tremelimumab 75 mg every 4 weeks x 3 cycles

  • Cisplatin-based neoadjuvant chemotherapyDrug

    Also called Standard of care (SoC)

    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 groups in NCT03472274
Study groupRoleWhat they receive
Cisplatin-based neoadjuvant chemotherapyActive comparatorPatients 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
Receives: Drug: Cisplatin-based neoadjuvant chemotherapy
Durvalumab plus TremelimumabExperimentalPatients randomized to experimental arma will receive 28-day treatment cycle x 3 cycles of Durvalumab + Tremelimumab 75 mg every 4 weeks
Receives: Drug: Durvalumab; Drug: Tremelimumab

What is being measured

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

  1. Antitumor activity

    Evidence of residual disease based on pathological review of the surgical specimen

    Measured: 20 weeks

Secondary outcomes (4)

  1. Overall Objective Response Rate

    Number of complete response (CR) or partial response (PR) according to RECIST v1.1.

    Measured: 20 weeks

  2. Disease Free Survival

    Number of disease recurrences according to RECIST v1.1 or death due to any cause, whichever occurs first

    Measured: 2 years

  3. Overall Survival

    Number of deaths due to any cause

    Measured: 2 years

  4. Incidence of Adverse Events

    Number of Adverse Events per patient using the National Cancer Institute Common Toxicity Criteria (CTC)

    Measured: 20 weeks

Timeline

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

  1. First posted21 Mar 2018
  2. Study start25 Oct 2018
  3. Primary completion30 Apr 2021
  4. Study completion12 Apr 2023

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
Masking
None (open label)
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03472274
Sponsor's protocol ID
DUTRENEO
Other IDs
2017-002246-68, 2017
Acronym
DUTRENEO
Status last verified
Apr 2023
First submitted
14 Mar 2018
Last updated
13 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Sibai M, Cervilla S, Grases D, Musulen E, Lazcano R, Mo CK, Davalos V, Fortian A, Bernat A, Romeo M, Tokheim C, Barretina J, Lazar AJ, Ding L; DUTRENEO Study Investigators; Grande E, Real FX, Esteller M, Bailey MH, Porta-Pardo E. The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity. Cell Rep. 2025 Feb 25;44(2):115229. doi: 10.1016/j.celrep.2024.115229. Epub 2025 Jan 24.

    PubMed 39864059

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab, Tremelimumab and Cisplatin-based neoadjuvant chemotherapy in people with Bladder Cancer, run by Fundacion CRIS de Investigación para Vencer el Cáncer at 11 sites in Spain.

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 21 inclusion and 35 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 13 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Spain. 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?

Antitumor activity (time frame: 20 weeks). 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 NCT03472274, which also lists 1 linked publication.

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 13 Apr 2023.

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