Infiltrating Bladder Urothelial CarcinomaPhase 1/2NEMIONCT03549715
NEoadjuvant Dose-dense MVAC In cOmbination With Durvalumab and Tremelimumab in Muscle-invasive Urothelial Carcinoma
A Phase 1/2 study testing Durvalumab, Tremelimumab and MVAC Protocol in people with Infiltrating Bladder Urothelial Carcinoma, run by Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie at 15 sites in France.
Trial summary
This is an open label, phase I/II clinical trial to evaluate the efficacy and safety of 2 cycles of durvalumab without (Arm A) or with (Arm B) tremelimumab in association with ddMVAC as neoadjuvant therapy in patients with MIUC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infiltrating Bladder Urothelial Carcinoma
- What is being tested?
- Durvalumab, Tremelimumab and MVAC Protocol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 121 participants
- Where
- 15 sitesFrance
- Study dates
- 6 Dec 2018to Sep 2025
- Phase
- Phase 1/2
- 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
- Written informed consent and any locally required authorization (e.g., EU Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
- Age ≥18 years at time of study entry
- Histologically confirmed MIUC (also termed TCC) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern (urothelial carcinoma must be > 50%)
- Localized MIUC of the bladder with clinical stage T2-T4a and ≤N1 disease ( the single lymph node must be < 15 mm (short axis) on imaging
- Patients with urothelial carcinoma of the prostatic urethra
- Bodyweight >45kg
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- Patients eligible for cisplatin-based neoadjuvant chemotherapy, including:
- Creatinine clearance (CL) >60 mL/min based on the Modification of Diet in Renal Disease Study (MDRD) formula
- Cardiac left ventricular ejection fraction (LVEF) ≥50%
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Absence of metastasis, as confirmed by a negative baseline CT or MRI scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization. Patients with clinical stage N1 disease are eligible if the single lymph node measures ≤2 cm in greatest dimension.
- Adequate organ and marrow function as defined below (obtained within 14 days prior to the first study treatment):
- Hemoglobin ≥10.0 g/dL (patients may be transfused to meet this criterion)
- Absolute neutrophil count (ANC) ≥1500 cells/μL (without G-CSF support within 2 weeks prior to Cycle 1, Day 1)
- WBC counts >2500/µL
- Platelet count ≥100,000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
- Serum bilirubin ≤1.0 x institutional upper limit of normal (ULN). Patients with known Gilbert disease who have serum bilirubin level ≤3 x ULN may be enrolled.
- AST, ALT, and alkaline dehydrogenase ≤2.5 x ULN
- Partial thromboplastin time/prothrombin time (PTT/PT) ≤1.5 x ULN or international normalized ratio (INR) <1.7 x ULN
- 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. The following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
- Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
- Women of childbearing potential and non-sterilized males who are sexually active with a female partner of childbearing potential must be willing to use contraceptive methods during the treatment period and for at least 6 months after the last dose of treatment
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Who cannot join
- Urothelial carcinoma of the upper tract
- Any approved anti-cancer therapy for urothelial carcinoma, including chemotherapy, or immunotherapy prior to initiation of study treatment. Of note, previous intravesical BCG injections are allowed if administered for non-muscle invasive urothelial carcinoma
- Primary chemoradiation for bladder preservation for urothelial carcinoma of the bladder
- Impaired renal function (glomerular filtration rate [GFR]<60 mL/min); GFR should be assessed by calculation from serum/plasma creatinine (MDRD formula)
- 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
- Grade 2 or greater hearing loss that contraindicates cisplatin use. Threshold shift of >25 decibel averaged at 2 contiguous test frequencies in least one ear.
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- Exception: Patients with Grade 2 hearing loss diagnosed on the audiogram that are asymptomatic (no complain of hearing loss and no tinnitus) can be enrolled in the study.
- Grade 2 or greater peripheral neuropathy
- Oral anticoagulation treatment (vitamin K antagonist should be replaced by low-molecular-weight heparin).
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
- Major surgical procedure (as defined by the Investigator) other than for diagnosis within 28 days prior to Cycle 1
- History of prior organ transplantation, including stem cell allografting
- History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and type I diabetes mellitus on stable dose of insulin may be eligible for this study
- All micropapillary and plasmacytic forms, with or without squamous cell adenocarcinoma
- Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
- Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
- Receipt of therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina
- History of another primary malignancy within 3 years prior to Cycle 1, Day 1, except for:
- Localized low-risk prostate cancer (defined as Stage ≤T2b, Gleason score ≤7, and prostate-specific antigen [PSA] at prostate cancer diagnosis ≤20 ng/mL [if measured]) treated with curative intent and without PSA recurrence Low-risk prostate cancer (defined as Stage T1/T2a, Gleason score <7, and PSA ≤10 ng/mL) who are treatment-naive and undergoing active surveillance Patients with malignancies of a risk of metastasis/death (e.g., risk of metastasis or death <5% at 5 years) are eligible after investigator's approval if they meet both of the following criteria: Malignancy treated with expected curative intent, and no evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers
- History of leptomeningeal carcinomatosis
- History of idiopathic pulmonary fibrosis, organizing pneumonia
- Serum albumin <25 g/L
- LVEF <50%
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 electrocardiograms (ECGs) within 15 minutes at 5 minutes apart
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive 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 PCR is negative for HCV RNA
- 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 (e.g., intra articular injection) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Patients, if enrolled, should not receive live vaccine whilst receiving study treatment and for up to 30 days after the last dose of study treatment
- Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy
- Known allergy or hypersensitivity to chimeric or humanized antibodies or fusion proteins, or to any of the study drugs or study drug excipients
- Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that, in the opinion of the Investigator, makes the patient unsuitable for participation in the study Procedures for withdrawal of incorrectly enrolled patients are presented in Section 4.3 If a patient withdraws from participation in the study, then his or her enrollment/randomization code cannot be reused. Withdrawn patients will not be replaced.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
France15 sites
Hôpital Saint André, CHU de Bordeaux
Bordeaux, 33075
Sasu Roc37
Chambray-lès-Tours, 37170
CHU Henri-Mondor
Créteil, 94000
Centre Leon Berard
Lyon, 69008
Institut Paoli Calmettes
Marseille, 13009
Centre Antoine Lacassagne
Nice, 06100
Groupe Hospitalier Pitié-Salpetrière
Paris, 75013
Institut Mutualiste Montsouris
Paris, 75014
Hôpital Cochin
Paris, 75679
Hôpital Européen Georges Pompidou
Paris, Île-de-France Region, 75015
Centre Eugène Marquis
Rennes, 35042
Hia Begin
Saint-Mandé, 94160
Hôpitaux universitaires de Strasbourg
Strasbourg, 67000
Institut Claudius Regaud
Toulouse, 31059
Institut Gustave Roussy
Villejuif, 94805
About this study
Official title: NEoadjuvant Dose-dense MVAC In cOmbination With Durvalumab (MEDI4736) and Tremelimumab in Muscle-invasive Urothelial Carcinoma
This is an open label, phase I/II clinical trial to evaluate the efficacy and safety of 2 cycles of durvalumab without (Arm A) or with (Arm B) tremelimumab in association with ddMVAC as neoadjuvant therapy in patients with MIUC.
Read the detailed description
Study Population:
Patients with MIUC fit to receive cisplatin.
Study Design:
The trial is designed as a non-comparative, open-label phase I/II study.
Divided in two phases:
The run In phase (I) and a phase II study. During the run-in phase, a limited number of patients (n=12-18) will be treated with durvalumab + ddMVAC or durvalumab + tremelimumab + ddMVAC (6-9 patients each). If the toxicity rate is acceptable (not higher than 2 out of 6 or 3 out of 9 patients per arm) the study will continue as a randomized phase II study. During phase II, the efficacy and safety of durvalumab + ddMVAC and durvalumab + tremelimumab + ddMVAC
Research hypothesis:
Combination of checkpoint inhibitors (CPI), durvalumab ± tremelimumab, with neoadjuvant ddMVAC will improve the pathological complete response (pCR) rate in patients with muscle-invasive urothelial carcinoma (MIUC). No additional toxicity of the combination CPI + ddMVAC is expected.
Investigational Product(s):
Durvalumab: 1500 mg IV D1 every 28 days Durvalumab will be administered at the hospital every 28 days prior to administration of ddMVAC on D1.
Tremelimumab 75 mg IV D1 every 28 days Tremelimumab will be administered first, with durvalumab infusion starting approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion.
Translational research:
Mechanism of response/resistance to neoadjuvant treatment will be assessed by comparing molecular and immunological tumor profiles before treatment (transurethral resection tumor samples) and after treatment (cystectomy samples). In addition, circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) will be analysed during treatment (ctDNA and utDNA) and after surgery (ctDNA).
Immunological profiles will be established using a specific metagene signature for major cell types of the tumor microenvironment and chemokines, cytokines and regulatory molecules , and will be validated using relevant markers by immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) tumor sections.
Metabolomic profiling will also be conducted by analyzing metabolites present in urinary samples with a Proton-based nuclear magnetic resonance (1H-NMR), and correlations with prognosis, molecular profile or/and with immunological signature determined.
Finally, correlations between tumor pathological factors (e.g., pTNM, nuclear grade, variant squamous differentiation or sarcomatoid dedifferentiation) and prognosis will be evaluated using IHC on FFPE tissue sections.
Sample Size: Approximately 121 patients are planned to be included.
- Being tested
- Durvalumab, Tremelimumab, MVAC Protocol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
1500 mg IV D1 every 28 days (2 doses for each patient)
TremelimumabDrug
Also called CP-675,206
75 mg IV D1 every 28 days ((2 doses for each patient)
MVAC ProtocolDrug
Also called ddMVAC
- Methotrexate 30 mg/m2 IV D1
- Vinblastine 3 mg/m2 IV D1
- Adriamycin (doxorubicin) 30 mg/m2 IV D1
- Cisplatin 70 mg/m2 IV D1
| Study group | Role | What they receive |
|---|---|---|
| ARM A: durvalumab + ddMVAC | Experimental | Durvalumab + ddMVAC Durvalumab 1500 mg IV D1 every 28 days Durvalumab will be administered at the hospital every 28 days prior to administration of ddMVAC on D1. Receives: Drug: Durvalumab; Drug: MVAC Protocol |
| ARM B: durvalumab + tremelimumab+ ddMVAC | Experimental | durvalumab + tremelimumab + ddMVAC Tremelimumab 75 mg IV D1 every 28 days Tremelimumab will be administered first, with durvalumab infusion starting approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion.
Infusion of ddMVAC will start approximately 1 hour after completion of durvalumab. Receives: Drug: Durvalumab; Drug: Tremelimumab; Drug: MVAC Protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity Grade
Grade ≥ 3 treatment related toxicity rate
Measured: 68 months
pathologic complete response
pCR rate after ddMVAC + durvalumab ± tremelimumab period
Measured: 1 year
Secondary outcomes (4)
Disease-Free Survival (DFS)
To evaluate the 2-year disease-free survival (DFS) rate.
Measured: 2 years
Overall Survival (OS)
To evaluate the 2-year overall survival (OS) rate
Measured: 2 years
Adverse Events (AEs).
To evaluate the incidence of adverse events (AEs).
Measured: 68 months
Pathologic downstaging
To evaluate the pathologic downstaging rate (defined as the presence of residual tumor ≤T1 on cystectomy, excluding T0).
Measured: During procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2018
- Study start6 Dec 2018
- Primary completionJun 2024 (estimated)
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Infiltrating Bladder Urothelial CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The sample size will be balanced between 2 arms. Initially, 12 patients (6 in each arm) will be included and randomized between durvalumab + ddMVAC (ARM A) or durvalumab + tremelimumab + ddMVAC (ARM B)
- Masking
- None (open label)
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Constance THIBAULT, MD, Principal investigator, Hôpital Européen Georges Pompidou, Oncology department of Pr Stéphane OUDARD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03549715
- Sponsor's protocol ID
- NEMIO
- Acronym
- NEMIO
- Status last verified
- Mar 2024
- First submitted
- 15 May 2018
- Last updated
- 6 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share
Publications
Thibault C, Bennamoun M, Flechon A, Gravis G, Pouessel D, Combe P, Borchiellini D, Loriot Y, Laguerre B, Barthelemy P, Huillard O, Gross-Goupil M, Le Roy A, Jaffrelot L, Cancel M, Audenet F, Belhouari H, Kaci G, Lepicard E, Vernerey D, Henriques J, Oudard S. Neoadjuvant Durvalumab +/- Tremelimumab in Combination With Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Carcinoma: Results of the Phase I/II NEMIO Study. J Clin Oncol. 2026 Jul 10;44(20):1921-1932. doi: 10.1200/JCO-25-03045. Epub 2026 May 26.
PubMed 42190158Thibault C, Elaidi R, Vano YA, Rouabah M, Braychenko E, Helali I, Audenet F, Oudard S. Open-label phase II to evaluate the efficacy of NEoadjuvant dose-dense MVAC In cOmbination with durvalumab and tremelimumab in muscle-invasive urothelial carcinoma: NEMIO. Bull Cancer. 2020 Jun;107(5S):eS8-eS15. doi: 10.1016/S0007-4551(20)30281-2.
PubMed 32620213
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NEoadjuvant Dose-dense MVAC In cOmbination With Durvalumab (MEDI4736) and Tremelimumab in Muscle-invasive Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT03549715
- Acronym / sponsor ID
- NEMIO / NEMIO
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Association Pour La Recherche des Thérapeutiques Innovantes en CancérologieUniversity, hospital or other
- Study start
- 6 Dec 2018 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Sep 2025 (estimated)
- First posted
- 8 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, phase I/II clinical trial to evaluate the efficacy and safety of 2 cycles of durvalumab without (Arm A) or with (Arm B) tremelimumab in association with ddMVAC as neoadjuvant therapy in patients with MIUC.
Detailed description
Study Population:
Patients with MIUC fit to receive cisplatin.
Study Design:
The trial is designed as a non-comparative, open-label phase I/II study.
Divided in two phases:
The run In phase (I) and a phase II study. During the run-in phase, a limited number of patients (n=12-18) will be treated with durvalumab + ddMVAC or durvalumab + tremelimumab + ddMVAC (6-9 patients each). If the toxicity rate is acceptable (not higher than 2 out of 6 or 3 out of 9 patients per arm) the study will continue as a randomized phase II study. During phase II, the efficacy and safety of durvalumab + ddMVAC and durvalumab + tremelimumab + ddMVAC
Research hypothesis:
Combination of checkpoint inhibitors (CPI), durvalumab ± tremelimumab, with neoadjuvant ddMVAC will improve the pathological complete response (pCR) rate in patients with muscle-invasive urothelial carcinoma (MIUC). No additional toxicity of the combination CPI + ddMVAC is expected.
Investigational Product(s):
Durvalumab: 1500 mg IV D1 every 28 days Durvalumab will be administered at the hospital every 28 days prior to administration of ddMVAC on D1.
Tremelimumab 75 mg IV D1 every 28 days Tremelimumab will be administered first, with durvalumab infusion starting approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion.
Translational research:
Mechanism of response/resistance to neoadjuvant treatment will be assessed by comparing molecular and immunological tumor profiles before treatment (transurethral resection tumor samples) and after treatment (cystectomy samples). In addition, circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) will be analysed during treatment (ctDNA and utDNA) and after surgery (ctDNA).
Immunological profiles will be established using a specific metagene signature for major cell types of the tumor microenvironment and chemokines, cytokines and regulatory molecules , and will be validated using relevant markers by immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) tumor sections.
Metabolomic profiling will also be conducted by analyzing metabolites present in urinary samples with a Proton-based nuclear magnetic resonance (1H-NMR), and correlations with prognosis, molecular profile or/and with immunological signature determined.
Finally, correlations between tumor pathological factors (e.g., pTNM, nuclear grade, variant squamous differentiation or sarcomatoid dedifferentiation) and prognosis will be evaluated using IHC on FFPE tissue sections.
Sample Size: Approximately 121 patients are planned to be included.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The sample size will be balanced between 2 arms. Initially, 12 patients (6 in each arm) will be included and randomized between durvalumab + ddMVAC (ARM A) or durvalumab + tremelimumab + ddMVAC (ARM B)
| Arm | Type | Receives |
|---|---|---|
| ARM A: durvalumab + ddMVAC | Experimental | Drug: Durvalumab, Drug: MVAC ProtocolDurvalumab + ddMVAC Durvalumab 1500 mg IV D1 every 28 days Durvalumab will be administered at the hospital every 28 days prior to administration of ddMVAC on D1. |
| ARM B: durvalumab + tremelimumab+ ddMVAC | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Drug: MVAC Protocoldurvalumab + tremelimumab + ddMVAC Tremelimumab 75 mg IV D1 every 28 days Tremelimumab will be administered first, with durvalumab infusion starting approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion. Infusion of ddMVAC will start approximately 1 hour after completion of durvalumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Written informed consent and any locally required authorization (e.g., EU Data Privacy Directive in the EU) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations
- Age ≥18 years at time of study entry
- Histologically confirmed MIUC (also termed TCC) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern (urothelial carcinoma must be > 50%)
- Localized MIUC of the bladder with clinical stage T2-T4a and ≤N1 disease ( the single lymph node must be < 15 mm (short axis) on imaging
- Patients with urothelial carcinoma of the prostatic urethra
Key exclusion criteria (35 listed)
- Urothelial carcinoma of the upper tract
- Any approved anti-cancer therapy for urothelial carcinoma, including chemotherapy, or immunotherapy prior to initiation of study treatment. Of note, previous intravesical BCG injections are allowed if administered for non-muscle invasive urothelial carcinoma
- Primary chemoradiation for bladder preservation for urothelial carcinoma of the bladder
- Impaired renal function (glomerular filtration rate [GFR]<60 mL/min); GFR should be assessed by calculation from serum/plasma creatinine (MDRD formula)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: MEDI47361500 mg IV D1 every 28 days (2 doses for each patient) | Drug | ARM A: durvalumab + ddMVAC, ARM B: durvalumab + tremelimumab+ ddMVAC |
| TremelimumabAlso: CP-675,20675 mg IV D1 every 28 days ((2 doses for each patient) | Drug | ARM B: durvalumab + tremelimumab+ ddMVAC |
| MVAC ProtocolAlso: ddMVAC1. Methotrexate 30 mg/m2 IV D1 2. Vinblastine 3 mg/m2 IV D1 3. Adriamycin (doxorubicin) 30 mg/m2 IV D1 4. Cisplatin 70 mg/m2 IV D1 | Drug | ARM A: durvalumab + ddMVAC, ARM B: durvalumab + tremelimumab+ ddMVAC |
Primary outcome
Toxicity Grade
Time frame: 68 months
Grade ≥ 3 treatment related toxicity rate
pathologic complete response
Time frame: 1 year
pCR rate after ddMVAC + durvalumab ± tremelimumab period
4 secondary outcomes
Disease-Free Survival (DFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Adverse Events (AEs).
Time frame: 68 months
Pathologic downstaging
Time frame: During procedure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Derived from this study: PubMed 42190158Thibault C, Bennamoun M, Flechon A, Gravis G, Pouessel D, Combe P, Borchiellini D, Loriot Y, Laguerre B, Barthelemy P, Huillard O, Gross-Goupil M, Le Roy A, Jaffrelot L, Cancel M, Audenet F, Belhouari H, Kaci G, Lepicard E, Vernerey D, Henriques J, Oudard S. Neoadjuvant Durvalumab +/- Tremelimumab in Combination With Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Carcinoma: Results of the Phase I/II NEMIO Study. J Clin Oncol. 2026 Jul 10;44(20):1921-1932. doi: 10.1200/JCO-25-03045. Epub 2026 May 26.
- Derived from this study: PubMed 32620213Thibault C, Elaidi R, Vano YA, Rouabah M, Braychenko E, Helali I, Audenet F, Oudard S. Open-label phase II to evaluate the efficacy of NEoadjuvant dose-dense MVAC In cOmbination with durvalumab and tremelimumab in muscle-invasive urothelial carcinoma: NEMIO. Bull Cancer. 2020 Jun;107(5S):eS8-eS15. doi: 10.1016/S0007-4551(20)30281-2.
- Individual participant dataSharing planned: No. No plan to share
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Urothelial Carcinoma, Muscle Invasive Bladder Urothelial Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Constance THIBAULT, MD principal investigator
Hôpital Européen Georges Pompidou, Oncology department of Pr Stéphane OUDARD
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Durvalumab, Tremelimumab and MVAC Protocol in people with Infiltrating Bladder Urothelial Carcinoma, run by Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie at 15 sites in France.
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 24 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: status not confirmed, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
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?
Toxicity Grade (time frame: 68 months). The study lists 2 primary outcomes in all. 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 NCT03549715, 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 6 Mar 2024.