AzTrials
AzTrials

Bladder CancerPhase 1/2DURANCENCT04106115

DURvalumab in Combination With S-488210/S-488211 vAccine in Non-muscle Invasive Bladder CancEr

A Phase 1/2 study testing Durvalumab and S-488210/S-488211 in people with Bladder Cancer, run by University College, London at 7 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

DURANCE is a two part, phase Ib/II, multi-centre study to assess the safety and activity of S-488210/S-488211 in combination with durvalumab, in patients with non-muscle invasive bladder cancer (NMIBC). 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 and S-488210/S-488211
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
7 sitesUnited Kingdom
Study dates
25 Mar 2022to 30 Sep 2032
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Histologically proven high risk non-muscle invasive bladder cancer (NMIBC)
  • Adequate archival tissue sample available for histological assessment (date sample taken must be within 6 months of planned start of treatment)
  • Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
  • Bacillus Calmette-Guerin (BCG) unresponsive disease or are intolerant of BCG therapy
  • Refused or deemed clinically inappropriate for radical cystectomy
  • ≥18 years of age
Show all 27Show fewer
  • Body weight >30 kg
  • World Health Organisation (WHO) performance status 0-1
  • Must have undergone each of the following procedures within 8 weeks of registration:
  • Complete excision of all papillary disease (T1/TaHG) and demonstration of no muscle invasive disease in the resected specimens (muscle must be present in the tumour sample)
  • Bladder 'Mapping biopsies' taken
  • CT of the chest
  • CT Urogram or MRI of the abdomen and pelvis (if CT is not possible)
  • Adequate haematological status:
  • Haemoglobin ≥9.0 g/dL
  • Absolute neutrophil count ≥1.5 x 10^9/L (≥150,000 per mm3)
  • Platelet count ≥100 x 10^9/L (≥100,000 per mm3)
  • International Normalised Ratio (INR) ≤1.5 and Activated Partial Thromoplastin Time (APTT) ≤1.5 x Upper Limit Normal (ULN). NB: This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
  • Adequate liver function:
  • Total bilirubin ≤1.5 X ULN (<3.0 x ULN for patients with Gilbert's syndrome)
  • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≤2.5 x ULN
  • Adequate renal function: Measured creatinine clearance ≥40 mL/min or calculated creatinine clearance ≥40 mL/min using Cockcroft-Gault formula.
  • Life expectancy of ≥6 months
  • Willing and able to give informed consent (which includes compliance with the requirements and restrictions listed in the patient information sheet (PIS) and in this protocol). NB: Consent must be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
  • Patients of child-bearing potential and male patients with female partners of child-bearing potential must agree to use highly effective contraception methods from date of consent, which must be continued for up to 90 days after last treatment administration.
  • Female patients must not be pregnant. There should be sufficient evidence of post-menopausal status or a negative serum pregnancy test for pre-menopausal female patients.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and any other study procedures.

Who cannot join

  • Any history of autoimmune or inflammatory disease including (any patients with a history of an autoimmune condition but without active disease in the last 5 years may be included only after consultation with the CI/TMG):
  • Inflammatory bowel disease (e.g. colitis or Crohn's disease)
  • Diverticulitis (with the exception of diverticulosis)
  • Systemic lupus erythematous (SLE)
  • Sarcoidosis syndrome
  • Wegener syndrome (granulomatosis with polyangitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
Show all 41Show fewer
  • Patients with prior allogeneic stem cell or solid organ transplantation
  • Patients who have had prior treatment with anti- PD-1, PD-L1 or CTLA-4 monoclonal antibody or other novel immune-oncology agent(s)
  • Active invasive malignancy in the previous 2 years excluding non-melanoma skin cancer
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia) or evidence of active pneumonitis on screening chest CT scan (history of radiation pneumonitis in the radiation field is permitted)
  • Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • QTcF value of >470 ms. If prolonged, this should be confirmed by 2 further ECGs each separated by at least 5 minutes.
  • Patients with the following risk factors for bowel perforation:
  • History of acute diverticulitis or intra-abdominal abcess in the last 3 years
  • History of mechanical GI obstruction or abdominal carcinomatosis
  • Any unresolved toxicity CTCAE Grade ≥2 from previous anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with any irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the CI/TMG
  • Receipt of last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, embolisation, monoclonal antibodies) within 30 days prior to first dose of trial treatment. NB: If sufficient washout time has not occurred due to the schedule or pharmacokinetic (PK) properties of an agent, a longer washout period will be required, as agreed by the Trial Management Group (TMG) and/or Chief Investigator (CI).
  • Treatment with any experimental drug within 30 days or 5 half-lives (whichever is longer) of the first dose of trial treatment
  • 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 evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial
  • Received therapeutic oral antibiotics that cannot be discontinued at least 14 days prior to starting treatment or received intravenous (IV) antibiotics within 14 days prior to registration. NB: Patients receiving prophylactic antibiotics (e.g. for prevention of a urinary tract infection or COPD) are eligible
  • Any psychiatric or other disorder (e.g. brain metastases) that impacts the patients ability to give informed consent or comply with trial treatment and activities
  • History of leptomeningeal carcinomatosis
  • Active infection of tuberculosis (TB) (clinically evaluated in accordance with local guidelines, e.g. clinical history, examination and radiographic findings with or without TB testing as clinically indicated)
  • Patients must not have had systemic corticosteroid therapy (>10 mg daily prednisolone equivalent) within 14 days prior to registration or concomitant use of other immunosuppressive medications. NB: The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids (i.e. for adrenal insufficiency) and mineralocorticoids (e.g. fludrocortisone) are allowed
  • Administration of a live, attenuated vaccine within 4 weeks prior to planned start of treatment or anticipation that such a live, attenuated vaccine will be required during the study
  • Evidence of significant uncontrolled concomitant disease that could substantially increase the risk of incurring adverse events (AEs), affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis), uncontrolled hypertension, serious chronic gastrointestinal conditions associated with diarrhoea and uncontrolled major seizure disorder
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of trial treatment. This does not include rigid cystoscopy and biopsies
  • Significant cardiovascular disease, such as:
  • New York Heart Association cardiac disease (Class II or greater)
  • Myocardial infarction within 3 months prior to registration
  • Unstable arrhythmias
  • Unstable angina
  • Patients with uncontrolled Type 1 diabetes mellitus. Patients controlled on a stable insulin regimen are eligible
  • Patients with uncontrolled adrenal insufficiency
  • Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
  • Known active primary immune deficiency, including but not limited to, uncontrolled human immunodeficiency virus (HIV) (detectable viral load) or acquired immunodeficiency syndrome (AIDS)-related illness
  • Women who are pregnant or breast feeding. Female or male patient of reproductive potential who is not willing to employ highly effective birth control from screening to 90 days after the last dose of trial treatment.
  • Known allergy or hypersensitivity to any of the investigational products or their excipients
  • Prior enrolment to, or treatment in a previous durvalumab clinical study, regardless of treatment arm assignment
  • Patients must not donate blood while participating in this study and for at least 90 days following the last dose of trial treatment

Trial locations and contacts

7 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Madison Williams contact

02076799514

ctc.durance@ucl.ac.uk

7 sites in 1 country

United Kingdom7 sites, 7 recruiting
  • Cambridge University NHS FT

    Cambridge

    Will Ince, MBBS, MRCGP, MRCP, FRCR

    Recruiting
  • Guy's and St Thomas' NHS Foundation Trust

    London

    Deborah Enting, MSc MBBS MRCP PGDip CCT

    Recruiting
  • Royal Free London NHS FT

    London

    Antonio Rullan, MBBS, MSc, PhD

    Recruiting
  • The Royal Marsden NHS Foundation Trust

    London

    Vincent Khoo, MBBS FRACR FRCR MD (Res)

    Recruiting
  • University College London Hospital NHS Foundation Trust

    London

    Mark Linch BSc (Hons) MBChB FRCP PhD

    Recruiting
  • The Christie NHS Foundation Trust

    Manchester

    Yee Pei Song, MB BCh BAO, MRCP, FRCR

    Recruiting
  • University Hospital Southampton NHS Foundation Trust

    Southampton

    Simon Crabb, BSc MBBS MRCP PhD CCT

    Recruiting

Other trials in United Kingdom

About this study

Official title: A Phase Ib/II Study to Assess the Safety and Activity of DURvalumab (MEDI4736) in Combination With S-488210/S-488211 vAccine in Non-muscle Invasive Bladder CancEr

DURANCE is a two part, phase Ib/II, multi-centre study to assess the safety and activity of S-488210/S-488211 in combination with durvalumab, in patients with non-muscle invasive bladder cancer (NMIBC).

Read the detailed description

DURANCE is a registered, phase Ib/II study in patients with surgically debulked bacillus Calmette-Guerin (BCG) unresponsive (resistant or relapsing) or intolerant non-muscle invasive bladder cancer (NIMBC). Patients will receive up to 24 weeks of durvalumab (a PD-L1 immune checkpoint inhibitor) in combination with S-488210/S-488211 (a 5-peptide cancer vaccine).

Durvalumab will be given as 1500 mg IV infusion every 4 weeks for up to 7 doses, in combination with S-488210/S-S488211 which will be administered as two subcutaneous injections of S-488210/Montanide and S-488211/Montanide starting the day after the first durvalumab dose, then weekly for 6 doses and every 2 weeks for a further 9 doses (up to a maximum of 16 doses).

All patients must have a cystoscopy at the end of week 12 (from start of trial treatment) for disease evaluation and to assess suitability to continue trial treatment. Patients with complete response, as shown from the cystoscopy, may continue treatment for up to 24 weeks in the absence of progressive disease, unacceptable toxicity or withdrawal of consent; all other patient will be withdrawn from further trial treatment.

The phase Ib part of the DURANCE study will look to assess the safety and tolerability of the treatment combination of durvalumab + S-488210/S-488211 by reviewing Dose Limiting Toxicities (DLTs) which have at least a reasonable possibility of being related to the trial treatments (durvalumab and/or S-488210/S-488211). Up to 14 evaluable patients will be registered into phase Ib and provided the DLTs do not exceed the DLT thresholds defined in the trial protocol, the trial will proceed to the expansion phase of the study (phase 2). In phase 2 the trial will look to assess the disease free survival rate at 1 year following start of treatment.

Conditions
Bladder Cancer
Being tested
Durvalumab, S-488210/S-488211
Keywords
Non-Muscle Invasive Bladder Cancer (NMIBC), Durvalumab, S-488210/S-488211, Immunotherapy, Vaccine, PD-L1 Inhibitor, BCG unresponsive
Medical subject headings
Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms

What participants receive

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

  • DurvalumabDrug

    Also called MEDI 4736

    1500 mg IV infusion every 4 weeks for up to 7 doses

  • S-488210/S-488211Biological

    Also called S-488210/Montanide, S-488211/Montanide

    S-488210/S-488211 is given as a 1 mL subcutaneous (SC) injection of S-488210/Montanide emulsion and a 1 mL SC injection of S-488211/Montanide emulsion starting the day after first dose of durvalumab and continuing weekly for 6 doses and then every 2 weeks for a further 9 doses

Study groups in NCT04106115
Study groupRoleWhat they receive
Durvalumab + S-488210/S-488211ExperimentalTrial treatment for up to 24 weeks of Durvalumab (1500 mg IV infusion every 4 weeks for up to 7 doses) in combination with S-488210/S-488211 vaccine (given as 2 subcutaneous injections of S-488210/Montanide and S-488211/Montanide starting day after first durvalumab dose, then weekly for the first 6 weeks, and then every 2 weeks for a further 9 doses).
Receives: Drug: Durvalumab; Biological: S-488210/S-488211

What is being measured

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

  1. Occurrence of Dose Limiting Toxicity (Phase 1b)

    Detailed adverse event monitoring will be conducted, assessed using CTCAE v5. Dose Limiting Toxicity (DLT) is defined as any adverse event or laboratory abnormality detailed in the trial protocol, that has a reasonable possibility of being related to trial treatment and occurring at anytime during the DLT evaluation period (28 days from the first administration of S-488210/S-488211 on cycle 1 day 2).

    Measured: At the end of cycle 1 (cycle 1 is 28 days)

  2. Pathological Disease Free Survival Rate (DFSR) (Phase 2) from cystoscopy and mapping biopsies

    Disease Free Survival will be calculated from start of trial treatment (cycle 1 day 1) until the time at which either primary disease is confirmed to have recurred, any secondary cancer is confirmed or death from any cause. The primary endpoint of Disease Free Survival Rate will be assessed at 1 year from start of treatment (and include patients that start trial treatment and receive combination treatment on cycle 2 day 1) and compared to the historical control rate of 20%.

    Measured: 1 year after start of treatment

Secondary outcomes (6)
  1. 1 year DFSR stratified by HLA-A*02:01

    If the primary endpoint (DFSR) is statistically signification, comparison of DFSR at 1 year will be conducted between patients that are human leukocyte antigen-A (HLA-A*02:01) positive versus negative.

    Measured: 1 year after start of treatment

  2. Overall Survival rate

    Overall survival will be assessed from time of starting treatment to time of death from any cause.

    Measured: Start of treatment to date of death, if applicable, or up to 60 months after last patient enrolled.

  3. 5 year Overall Survival rate stratified by HLA-A*02:01

    Overall survival will be assessed from time of starting treatment to time of death from any cause, stratified by HLA-A*02:01 positive or negative.

    Measured: 5 years from start of treatment to date of death, if applicable, or up to 60 months after last patient enrolled.

  4. Assessment of Quality of Life using EORTC QLQ-C30 questionnaire

    Quality of Life assessments will be undertaken using EORTC QLQ-C30 (version 3) questionnaire using Likert score (26 questions scored: 1=not at all, 2=a little, 3=quite a bit, 4=very much; 2 questions scored: 1-7, 1=very poor, 7=excellent) . Descriptions of mean change in EORTC QLQ scores will be presented and compared to baseline values from pre-treatment.

    Measured: Assessments will be performed at baseline (prior to starting treatment on cycle 1 days 1), every 12 weeks up to 12 months after start of treatment and 24 months after start of treatment.

  5. Assessment of Quality of Life using EORTC QLQ-NMIBC24 questions

    Quality of Life assessments will be undertaken using EORTC QLQ-C30 which will include QLQ-NMIBC24 questions using Likert score (24 questions scored: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Descriptions of mean change in EORTC QLQ scores will be presented and compared to baseline values from pre-treatment.

    Measured: Assessments will be performed at baseline (prior to starting treatment on cycle 1 days 1), every 12 weeks up to 12 months after start of treatment and 24 months after start of treatment.

  6. Assessment of Quality of Life using EQ-5D-5L questionnaire

    Quality of Life assessments will be undertaken using EQ-5D-5L (self-reported) questionnaire using a combination of Likert score (5 questions with 5 dimensions of abilities) and visual analogue score (scored 0-100, 0=worst, 100=best). Descriptions of mean change in EQ-5D-5L scores will be presented and compared to baseline values from pre-treatment.

    Measured: Assessments will be performed at baseline (prior to starting treatment on cycle 1 days 1), every 12 weeks up to 12 months after start of treatment and 24 months after start of treatment.

Timeline

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

  1. First posted26 Sep 2019
  2. Study start25 Mar 2022
  3. Primary completion30 Mar 2027 (estimated)
  4. Study completion30 Sep 2032 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04106115
Sponsor's protocol ID
UCL/121881
Acronym
DURANCE
Status last verified
Jun 2026
First submitted
9 Sep 2019
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Durvalumab and S-488210/S-488211 in people with Bladder Cancer, run by University College, London at 7 sites in United Kingdom.

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 27 inclusion and 41 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: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United Kingdom. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Madison Williams (02076799514, ctc.durance@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurrence of Dose Limiting Toxicity (Phase 1b) (time frame: At the end of cycle 1 (cycle 1 is 28 days)). 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?
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 11 Jun 2026.

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