Muscle Invasive Bladder CancerPhase 1BISCAYNCT02546661

Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer

A Phase 1 study testing AZD4547, MEDI4736 and Olaparib in people with Muscle Invasive Bladder Cancer, run by AstraZeneca at 27 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 to 130 years
Conditions the study is for: Muscle Invasive Bladder Cancer
What is being tested?: AZD4547, MEDI4736 and Olaparib
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 117 participants
Where: 27 sitesin 5 countries
Study dates: 28 Dec 2016to 30 Nov 2026
Phase: Phase 1
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 to 130 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Metastatic MIBC
2nd/3rd line
Failed adjuvant/neo-adjuvant chemotherapy <1 yr
1 lesion ≥10 mm at baseline in the longest diameter suitable for accurate repeated measurement
WHO perf. status 0-1
For Module A:

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M/F ≥25
Confirmation of FGFR3 mutation or FGFR fusion
For Module B:
Hgb ≥10 g/dL
Deleterious mutation, deletion or truncation in any HRR genes
For Module C:
1. Tumour harbours a deletion or inactivating mutation of the CDKN2A or RB1 genes and/or amplification of CCNE1, MYC, MYCL or MYCN genes
For Module E:
1. Contraception must be sustained throughout treatment with vistusertib and 16 wks after last dose
For Module F:
Adequate organ and marrow function, defined as Leukocytes ≥3.0x10(exp9)/L; ANC ≥1.5x10(exp9)/L; platelets ≥100x10(exp9)/L
Contraceptive measures must be sustained throughout treatment with AZD9150 and for 180 days after the last dose.

Who cannot join

Immunotherapy, chemotherapy, anticancer agents, radiotherapy <4 weeks, or radiotherapy for palliation <2 weeks, any study drugs <30 days.
Major surgery <4 weeks
Unresolved toxicities from prior therapy
Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy
Immunosuppressive drugs <28 days
Any of the following: Autoimmune disease ≤2 yr; IBD; primary immunodeficiency; organ transplant requiring immunosuppressives

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Spinal cord compression or brain metastases, treated and stable \& not requiring steroids for at least 4 weeks
Severe or uncontrolled systemic disease
Any of the following: Mean QTc ≥470 ms; abnormalities in resting ECG; factors that increase the risk of QTc prolongation or arrhythmia; uncontrolled hyper/hypotension; LVEF <55%; atrial fibrillation; NYHA Grade II-IV; severe valvular disease; uncontrolled angina; stroke/TIA <6 months; acute coronary syndrome <6 months
Any of the following laboratory values: ANC <1.5x10(exp9)/L; Platelets <100x10(exp9)/L; Hgb <9.0 g/dL; ALT >2.5xULN or >5xULN with liver mets; Total bilirubin >1.5 times ULN or with Gilbert's disease ≥2×ULN; Creatinine >1.5xULN concurrent with creatinine clearance <50 mL/min; Corrected Ca >ULN, PO4 >ULN
Active infection including tuberculosis, hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus. Patients with a past or resolved HBV infection are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Live attenuated vaccination <30 days
For Module A:
Prior exposure to: Nitrosourea or mitomycin C <6 weeks; any agent with FGFR inhibition as its primary pharmacology; AZD4547; potent inhibitors/inducers of CYP3A4, inhibitors of CYP2D6 or substrates of CYP3A4 <2 wks
Ophthalmological criteria: RPED; laser treatment or intraocular injection for macular degeneration; age-related macular degeneration; retinal vein occlusion; retinal degenerative disease; other clinically relevant chorioretinal defect
Refractory nausea/vomiting, chronic GI diseases, or previous bowel resection
For Module B:
Transfusion <120 days
Concurrent medications that are strong inhibitors of cytochrome P450 (CYP) 3A (CYP3A) or strong inducers of CYP3A4.
Previous treatment with PARP inhibitor, including olaparib
Patients with history of MDS or AML
For Module C:
Prior exposure to any of the following: Nitrosourea or mitomycin C <6 wks; any agent with Wee1 inhibition as its primary pharmacology; prior treatment with AZD1775
Any drugs or products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with narrow therapeutic index, or moderate to strong inhibitors/inducers of CYP3A4
Herbal preparations
Refractory nausea and vomiting or chronic GI diseases
Cardiac disease <6 months
For Module E:
Minor surgery <14 days of first dose
Exposure to specific substrates of OATP1B1, OATP1B3, MATE1 and MATE2K <5x half-life before treatment. Exposure to strong/moderate inhibitors/inducers of CYP3A4/5, Pgp (MDR1) and BRCP if taken within washout periods before the first dose
Haemopoietic growth factors (filgrastim, sargramostim, GM-CSF) <14 days prior to treatment
Other mTOR inhibitors
Renal disease or renal tubular acidosis
Uncontrolled Type 1 or 2 diabetes
For Module F:
1. AST ≤ 2.5xULN or ≤5xULN with liver metastases
For Module G:
Have had prior treatment with a MEK, Ras or Raf inhibitor.
Any of the following ophthalmic criteria: Current or past history of central serous retinopathy, detachment of retinal pigmented epithelium, or retinal vein occlusion; intraocular pressure (IOP) >21 mmHg; uncontrolled glaucoma (irrespective of IOP)
Baseline left ventricular ejection fraction (LVEF) <55% measured by echocardiogram (ECHO) or, if allowed, a multigated acquisition (MUGA) scan. Appropriate correction to be used if a MUGA is performed.
Previous moderate or severe impairment of LVEF (<45% on echocardiography or equivalent on MUGA) even if full recovery has occurred.
Male or female patients with reproductive potential and, as judged by the investigator, are not employing an effective method of birth control and female patients who are breastfeeding.
Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Receiving or have received systemic therapy with nitrosoureas, mitomycin or suramin within 6 weeks prior to starting study treatment.

Trial locations and contacts

27 sites in 5 countries.

Country

City, postcode or hospital

27 sites in 5 countries

United States8 sites

Research Site
Cleveland, Ohio, 44195
Research Site
Fort Myers, Florida, 33901
Research Site
Los Angeles, California, 90095
Research Site
Nashville, Tennessee, 37203
Research Site
New Haven, Connecticut, 06510
Research Site
New York, New York, 10029
Research Site
New York, New York, 10032
Research Site
New York, New York, 10116

Other trials in United States

France6 sites

Research Site
Bordeaux, 33075
Research Site
Caen, 14000
Research Site
Lyon, 69373
Research Site
Marseille, 13273
Research Site
Saint-Herblain, 44805
Research Site
Toulouse, 31100

Other trials in France

United Kingdom5 sites

Research Site
Glasgow, G12 0YN
Research Site
London, EC1M 6BQ
Research Site
London, W1G 6AD
Research Site
Manchester, M20 4BX
Research Site
Southampton, SO16 6YD

Other trials in United Kingdom

Canada4 sites

Research Site
Edmonton, Alberta, T6G 1Z2
Research Site
Montreal, Quebec, H3T 1E2
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Spain4 sites

Research Site
Badalona, 08003
Research Site
Barcelona, 08035
Research Site
Barcelona, 08041
Research Site
Madrid, 28040

Other trials in Spain

About this study

Official title: An Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Multi-Centre, Multi-arm Phase 1b Study in Patients With Muscle Invasive Bladder Cancer (MIBC) Who Have Progressed on Prior Treatment (BISCAY).

This is an open label, multi-drug, biomarker-directed, multi-centre, multi-arm, Phase 1b study in patients with muscle invasive bladder cancer (MIBC) (urothelial) who have progressed on prior treatment. This study is modular in design, allowing evaluation of the safety, tolerability, pharmacokinetics and anti-tumour activity of multiple agents as monotherapy and as combinations of different novel anti-cancer agents.

The study will consist of a number of study modules (sub-studies), each evaluating the safety and tolerability of a specific agent or combination.

Read the detailed description

The study will consist of a number of study modules (sub-studies), each evaluating the safety and tolerability of a specific agent or combination in patients whose tumours express specific genomic alterations relevant to the molecules under investigation and whose disease has progressed following prior therapy. The allocation of patients to specific modules will depend on the specific eligible genomic alterations identified in their tumours.

Each module will determine the appropriate combination dose for further clinical evaluation based on safety, tolerability and efficacy profile. A maximum tolerated dose will be defined and each arm expanded appropriately to explore further the safety, tolerability, pharmacokinetics and biological activity at the selected combination doses.

Module A includes an AZD4547 monotherapy arm and a MEDI4736 (durvalumab) + AZD4547 combination therapy arm and will investigate the safety and tolerability of MEDI4736 given intravenously, in combination with AZD4547 given orally to selected patients with MIBC with tumours that have fibroblast growth factor receptor mutations or fibroblast growth factor receptor fusions.

Module B will investigate the safety and tolerability of MEDI4736 given intravenously in combination with olaparib (AZD2281, Lynparza) given orally to selected patients with MIBC whose tumors have mutations in a homologous recombination repair gene panel and whose disease had progressed following prior therapy.

Module C will investigate the safety and tolerability of MEDI4736 given intravenously, in combination with AZD1775 given orally to selected patients with MIBC whose tumours have mutations in genes involved in cell cycle regulation (e.g., loss of either retinoblastoma 1 or cyclin-dependent kinase inhibitor 2A or amplification of cyclin E1 or MYC family genes).

Module D will investigate the safety and tolerability of MEDI4736 given intravenously as monotherapy to patients with MIBC who do not qualify for Modules A, B or C.

Module E will investigate the safety and tolerability of MEDI4736 given intravenously, in combination with vistusertib (AZD2014) given orally to patients with MIBC whose tumours do not show genomic alterations that would be eligible for other study modules. Patients whose MIBC tumours harbour the following genomic alterations that have potential to respond to a mammalian target of rapamycin (mTOR) inhibitor will also be included in Module E: RICTOR amplification, or TSC1/1 mutations.

Module F will investigate the safety and tolerability of MEDI4736 given intravenously in combination with AZD9150 given intravenously to patients with MIBC whose tumours do not show genomic alterations that would be eligible for other modules.

Module G will investigate the safety and tolerability of MEDI4736 given intravenously in combination with selumetinib (AZD6244) given orally to patients with MIBC. Patients in this module will not be selected for any specific tumour genomic alteration.

Conditions: Muscle Invasive Bladder Cancer
Being tested: AZD4547, MEDI4736, Olaparib, AZD1775, Vistusertib
Keywords: Durvalumab, Olaparib, Vistusertib, Selumetinib, Muscle invasive bladder cancer, MIBC, BISCAY, MEDI4736, AZD4547, AZD2281, AZD1775, AZD2014, AZD9150, AZD6244

What participants receive

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

AZD4547Drug
AZD4547 Monotherapy vs. MEDI4736 (durvalumab) + AZD4547 1:1 Randomization.
MEDI4736Drug
Also called Durvalumab
MEDI4736
OlaparibDrug
Also called Lynparza
MEDI4736 (durvalumab) + Olaparib
AZD1775Drug
MEDI4736 (durvalumab) + AZD1775
VistusertibDrug
MEDI4736 (durvalumab) + Vistusertib
AZD9150Drug
MEDI4736 (durvalumab) + AZD9150
SelumetinibDrug
MEDI4736 (durvalumab) + Selumetinib

Study groups in NCT02546661
Study group	Role	What they receive
Module A: AZD4547 Monotherapy	Experimental	AZD4547 will be given orally twice daily until disease progression. Patients who receive AZD4547 as monotherapy will have the option to cross over to durvalumab as monotherapy at the point of objective progression, as long as the following criteria are met: * The investigator believes it is in the patient's interest to receive durvalumab; * The patient consents to the continued treatment; * It is clinically appropriate for the patient to continue on durvalumab treatment; * The patient satisfies the key eligibility criteria for receiving durvalumab treatment. Receives: Drug: AZD4547
Module A: MEDI4736 (durvalumab) + AZD4547	Experimental	AZD4547 will be given orally twice daily until disease progression. Patients will also receive MEDI 4736 (durvalumab) by IV infusion once every 4 weeks. Receives: Drug: AZD4547; Drug: MEDI4736
Module B: MEDI4736 (durvalumab) + Olaparib	Experimental	MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Olaparib will be given orally twice daily. Receives: Drug: MEDI4736; Drug: Olaparib
Module C: MEDI4736 (durvaluamb) + AZD1775	Experimental	MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. AZD1775 will be given orally in approximate 12 hour intervals over 3 days (6 doses) on Days 1-3, 8-10, and 15-17 of 28 day cycles. Receives: Drug: MEDI4736; Drug: AZD1775
Module D: MEDI4736 (durvalumab) monotherapy	Experimental	MEDI 4736 (durvalumab) will be given by IV infusion once every 4 weeks. Receives: Drug: MEDI4736
Module E: MEDI4736 (durvalumab) + Vistusertib	Experimental	MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Vistusertib will be given orally twice per day on an intermittent schedule (2 days on, 5 days off). Receives: Drug: MEDI4736; Drug: Vistusertib
Module F: MEDI4736 (durvaluamb) + AZD9150	Experimental	AZD9150 will be given as monotherapy on Days -7, -5, and -3 of a one week lead-in period. Combination dosing with IV AZD9150 followed by IV MEDI4736 (durvalumab) begins on Day 1 of each 28 day cycle. Thereafter AZD9150 is given weekly and MEDI4736 is given once every 4 weeks. Receives: Drug: MEDI4736; Drug: AZD9150
Module G: MEDI4736 + Selumetinib	Experimental	Not described Receives: Drug: MEDI4736; Drug: Selumetinib

What is being measured

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

Module A: The frequency and nature of adverse events related to AZD4547 monotherapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of AZD4547 monotherapy given orally to selected patients with MIBC who have progressed following prior therapy.
Measured: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
Module A: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and oral AZD4547.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with AZD4547 given orally to selected patients with MIBC who have progressed following prior therapy.
Measured: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
Module B: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and oral olaparib.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with olaparib given orally to selected patients with MIBC who have progressed following prior therapy.
Measured: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
Module C: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral AZD1775.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with AZD1775 given orally to selected patients with MIBC who have progressed following prior therapy.
Measured: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
Module D: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) monotherapy.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) monotherapy given intravenously to selected patients with MIBC who have progressed following prior therapy.
Measured: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
Module E: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral vistusertib.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI 4736 (durvalumab) given intravenously in combination with vistusertib given orally to selected patients with MIBC who have progressed following prior therapy.
Measured: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
Module F: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and intravenous AZD9150.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of intravenous MEDI4736 (durvalumab) in combination with intravenous AZD9150 in selected patients with MIBC who have progressed following prior therapy.
Measured: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
Module G: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral selumetinib.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI 4736 (durvalumab) given intravenously in combination with selumetinib given orally to selected patients with MIBC who have progressed following prior therapy.
Measured: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
All Modules: Change from baseline in clinical chemistry parameters.
Changes from baseline in clinical chemistry parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
All Modules: Change from baseline in haematology parameters.
Changes from baseline in haemotology parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
All Modules: Change from baseline in urinalysis results.
Changes from baseline in urinalysis findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
All Modules: Change from baseline in vital signs.
Changes from baseline in vital signs will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: Day 1 of Cycles 1, 2, 3, and 4 and every 4 weeks therafter, and at discontinuation.
All Modules: Change from baseline in physical examination findings.
Changes from baseline in physical examination findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: Day 1 of Cycles 1, 2, 3, and 4 and every 4 weeks therafter, and at discontinuation.
All Modules: Change from baseline in ECG findings.
Changes from baseline in ECG findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: ECGs will be collected at screening, Day 1, Cycle 1and then Day 1 of each cycle from Cycle 2 onwards.
All Modules: Change from baseline in ejection fraction determined by assessing ECHO/MUGA scans.
Changes from baseline in ejection fraction determined by assessing ECHO/MUGA scans will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: Ejection fraction will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.
All Modules: Change from baseline in coagulation parameters
Changes from baseline in coagulation parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: Coagulation parameters will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.
All Modules: Change from baseline in lipid profile
Changes from baseline in lipid profile will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
Measured: Lipid profile will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.

Secondary outcomes (16)

Objective response rate (ORR)
The percentage of patients who have a confirmed visit response of Complete Response (CR) or Partial Response (PR) as assessed by the investigator per RECIST 1.1.
Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR.
Measured: 16 weeks and 52 weeks
Disease control rate (DCR)
Percentage of patients who have a confirmed visit response of CR or PR or stable disease (SD) ≥16 weeks as assessed by the investigator as per RECIST 1.1
Measured: 16 weeks and 52 weeks
Progression free survival (PFS)
The time from randomization until the date of objective disease progression or death (from any cause in the absence of progression) regardless of whether the patient withdraws from assigned therapy or receives another anticancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.
Measured: up to 12 months
Duration of response (DoR)
Duration of response is defined as the elapsed time from the date of first documented response (CR/PR) as per RECIST Version 1.1 as assessed by the investigator until the date of documented progression or death in the absence of disease progression. The time of the initial response is defined as the latest of the dates contributing towards the first visit response of PR or CR.
Measured: up to 12 months
Overall survival (OS) rate at 1 year
Defined as the proportion of patients surviving after 1 year from the start of treatment.
Measured: 1 year
Plasma concentration of AZD4547 (Module A)
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken pre-dose on Days 1 and 8 of Cycle 1; pre-dose and 2, 3, 4 and 6 hours post-dose on Day 1 of Cycle 2; and pre-dose and 2 to 4 hours post-dose on Day 1 of Cycle 3.
Plasma concentration of MEDI4736 (durvalumab) (Module A)
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and for the post-Cycle 7 8-weekly assessments, and pre-dose for Day 8 of Cycle 1.
Plasma concentration of olaparib (Module B)
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken on Day 3 of Cycles 1 and pre-dose and 4 hr post-dose. Serial samples on Day 3 of Cycle 3, pre-dose, 1, 2, 4, 6, 8, and 10 hr post-dose.
Plasma concentration of AZD1775 (Module C)
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken on Day 8 at steady state at the following time points: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hr post-dose.
Plasma concentration of MEDI4736 (durvalumab) (Module C)
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken on Days 1 and 8 of Cycle 1 pre-dose and at the end of infusion (1 hour). Samples will also be collected on Day 1 of Cycles 2 to 7 pre-dose and at the end of infusion.
Plasma concentration of MEDI4736 (durvalumab) (Module D)
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken on Days 1 and 8 of Cycle 1
Plasma concentration of vistusertib (Module E)
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be collected pre-dose, and 2 and 4 hr post-dose on Day 1 of Cycle 1; and pre-dose and 2 to 6 hr post-dose (matched to biopsy) on Day 2 of Cycle 2.
Plasma concentration of Medi4736 (durvalumab) (Module E).
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and every 8 weeks thereafter and pre-dose for Day 8 of Cycle 1.
Plasma concentration of AZD9150 (Module F)
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken pre-dose of Days -7, -5, and -3 of the lead-in portion and thereafter prior to dosing and at the ned of infusion on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (approximately 8 months).
Plasma concentration of MEDI4736 (durvalumab) (Module F).
The timing of the PK samples may be adjusted during the study, dependent on emerging data, in order to ensure appropriate characterisation of the plasma concentration-time profiles.
Measured: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and every 8 weeks thereafter and pre-dose for Day 8 of Cycle 1.
The presence of Anti-Drug Antibodies (ADA) and ADA neutralising antibodies to MEDI4736 will be assessed in patients receiving MEDI4736 in any sub-study module.
The formation of anti-drug antibodies and neutralizing antibodies will be assessed by validated methods.
Measured: Blood samples will be collected prior to MEDI4736 dosing on Day 1 of Cycles 1, 2 and 4 and every 12 weeks thereafter (up to 12 months).

Timeline

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

28 Dec 201630 Nov 2026

First posted11 Sep 2015 (estimated)
Study start28 Dec 2016
Primary completion18 Mar 2020
Study completion30 Nov 2026 (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 Muscle Invasive Bladder CancerStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
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
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 117 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02546661
Sponsor's protocol ID: D2615C00001
Other IDs: GU 118, BISCAY, 2015-002228-25, 2015
Acronym: BISCAY
Status last verified: Sep 2026
First submitted: 27 Aug 2015
Last updated: 1 Oct 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Publications

Powles T, Carroll D, Chowdhury S, Gravis G, Joly F, Carles J, Flechon A, Maroto P, Petrylak D, Rolland F, Cook N, Balar AV, Sridhar SS, Galsky MD, Grivas P, Ravaud A, Jones R, Cosaert J, Hodgson D, Kozarewa I, Mather R, McEwen R, Mercier F, Landers D. An adaptive, biomarker-directed platform study of durvalumab in combination with targeted therapies in advanced urothelial cancer. Nat Med. 2021 May;27(5):793-801. doi: 10.1038/s41591-021-01317-6. Epub 2021 May 3.
PubMed 33941921
Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.
PubMed 32203306

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
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Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
Testing the Addition of an Anti-cancer Drug, Pembrolizumab, to the Usual Intravesical Chemotherapy Treatment (Gemcitabine) for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer
Bladder Flat Urothelial Carcinoma In Situ, Non-Muscle Invasive Bladder Urothelial Carcinoma
RecruitingPhase 2
A Phase II Trial of Bicalutamide in Patients Receiving Intravesical BCG for Non-muscle Invasive Bladder Cancer
Non-Muscle Invasive Bladder Cancer
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Neoadjuvant Intravesical Nadofaragene Firadenovec With Gemcitabine, Cisplatin and Durvalumab for the Treatment of Muscle Invasive Bladder Cancer, TRIFECTA Trial
Muscle Invasive Bladder Urothelial Carcinoma, Stage II Bladder Cancer AJCC v8
Not yet recruitingObservational study
Outcomes for IR and High Risk (HR) Non-muscle Invasive Bladder Cancer (NMIBC) and ctDNA-based Biomarkers for Response and Recurrence in Muscle Invasive Bladder Cancer (MIBC)
NMIBC, MIBC

All Muscle Invasive Bladder Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Multi-Centre, Multi-arm Phase 1b Study in Patients With Muscle Invasive Bladder Cancer (MIBC) Who Have Progressed on Prior Treatment (BISCAY).
ClinicalTrials.gov ID: NCT02546661
Acronym / sponsor ID: BISCAY / D2615C00001
Conditions: Muscle Invasive Bladder Cancer
Keywords: Durvalumab, Olaparib, Vistusertib, Selumetinib, Muscle invasive bladder cancer, MIBC, BISCAY, MEDI4736
Phase: Phase 1
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 117 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 28 Dec 2016 (actual)
Primary completion: 18 Mar 2020 (actual)
Study completion: 30 Nov 2026 (estimated)
First posted: 11 Sep 2015 (estimated)
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.

The study will consist of a number of study modules (sub-studies), each evaluating the safety and tolerability of a specific agent or combination.

Detailed description

Module D will investigate the safety and tolerability of MEDI4736 given intravenously as monotherapy to patients with MIBC who do not qualify for Modules A, B or C.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Module A: AZD4547 Monotherapy	Experimental	Drug: AZD4547AZD4547 will be given orally twice daily until disease progression. Patients who receive AZD4547 as monotherapy will have the option to cross over to durvalumab as monotherapy at the point of objective progression, as long as the following criteria are met: * The investigator believes it is in the patient's interest to receive durvalumab; * The patient consents to the continued treatment; * It is clinically appropriate for the patient to continue on durvalumab treatment; * The patient satisfies the key eligibility criteria for receiving durvalumab treatment.
Module A: MEDI4736 (durvalumab) + AZD4547	Experimental	Drug: AZD4547, Drug: MEDI4736AZD4547 will be given orally twice daily until disease progression. Patients will also receive MEDI 4736 (durvalumab) by IV infusion once every 4 weeks.
Module B: MEDI4736 (durvalumab) + Olaparib	Experimental	Drug: MEDI4736, Drug: OlaparibMEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Olaparib will be given orally twice daily.
Module C: MEDI4736 (durvaluamb) + AZD1775	Experimental	Drug: MEDI4736, Drug: AZD1775MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. AZD1775 will be given orally in approximate 12 hour intervals over 3 days (6 doses) on Days 1-3, 8-10, and 15-17 of 28 day cycles.
Module D: MEDI4736 (durvalumab) monotherapy	Experimental	Drug: MEDI4736MEDI 4736 (durvalumab) will be given by IV infusion once every 4 weeks.
Module E: MEDI4736 (durvalumab) + Vistusertib	Experimental	Drug: MEDI4736, Drug: VistusertibMEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Vistusertib will be given orally twice per day on an intermittent schedule (2 days on, 5 days off).
Module F: MEDI4736 (durvaluamb) + AZD9150	Experimental	Drug: MEDI4736, Drug: AZD9150AZD9150 will be given as monotherapy on Days -7, -5, and -3 of a one week lead-in period. Combination dosing with IV AZD9150 followed by IV MEDI4736 (durvalumab) begins on Day 1 of each 28 day cycle. Thereafter AZD9150 is given weekly and MEDI4736 is given once every 4 weeks.
Module G: MEDI4736 + Selumetinib	Experimental	Drug: MEDI4736, Drug: Selumetinib

Who may qualify

Ages: 18 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (18 listed)

Metastatic MIBC
2nd/3rd line
Failed adjuvant/neo-adjuvant chemotherapy <1 yr
1 lesion ≥10 mm at baseline in the longest diameter suitable for accurate repeated measurement
WHO perf. status 0-1

Key exclusion criteria (44 listed)

Immunotherapy, chemotherapy, anticancer agents, radiotherapy <4 weeks, or radiotherapy for palliation <2 weeks, any study drugs <30 days.
Major surgery <4 weeks
Unresolved toxicities from prior therapy
Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy
Immunosuppressive drugs <28 days

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
AZD4547AZD4547 Monotherapy vs. MEDI4736 (durvalumab) + AZD4547 1:1 Randomization.	Drug	Module A: AZD4547 Monotherapy, Module A: MEDI4736 (durvalumab) + AZD4547
MEDI4736Also: DurvalumabMEDI4736	Drug	Module A: MEDI4736 (durvalumab) + AZD4547, Module B: MEDI4736 (durvalumab) + Olaparib, Module C: MEDI4736 (durvaluamb) + AZD1775, Module D: MEDI4736 (durvalumab) monotherapy, Module E: MEDI4736 (durvalumab) + Vistusertib, Module F: MEDI4736 (durvaluamb) + AZD9150, Module G: MEDI4736 + Selumetinib
OlaparibAlso: LynparzaMEDI4736 (durvalumab) + Olaparib	Drug	Module B: MEDI4736 (durvalumab) + Olaparib
AZD1775MEDI4736 (durvalumab) + AZD1775	Drug	Module C: MEDI4736 (durvaluamb) + AZD1775
VistusertibMEDI4736 (durvalumab) + Vistusertib	Drug	Module E: MEDI4736 (durvalumab) + Vistusertib
AZD9150MEDI4736 (durvalumab) + AZD9150	Drug	Module F: MEDI4736 (durvaluamb) + AZD9150
SelumetinibMEDI4736 (durvalumab) + Selumetinib	Drug	Module G: MEDI4736 + Selumetinib

Primary outcome

Module A: The frequency and nature of adverse events related to AZD4547 monotherapy.
Time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of AZD4547 monotherapy given orally to selected patients with MIBC who have progressed following prior therapy.
Module A: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and oral AZD4547.
Time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with AZD4547 given orally to selected patients with MIBC who have progressed following prior therapy.
Module B: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and oral olaparib.
Time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with olaparib given orally to selected patients with MIBC who have progressed following prior therapy.
Module C: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral AZD1775.
Time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) given intravenously in combination with AZD1775 given orally to selected patients with MIBC who have progressed following prior therapy.
Module D: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) monotherapy.
Time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI4736 (durvalumab) monotherapy given intravenously to selected patients with MIBC who have progressed following prior therapy.
Module E: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral vistusertib.
Time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI 4736 (durvalumab) given intravenously in combination with vistusertib given orally to selected patients with MIBC who have progressed following prior therapy.
Module F: The frequency and nature of adverse events related to the combination of intravenous MEDI4736 (durvalumab) and intravenous AZD9150.
Time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of intravenous MEDI4736 (durvalumab) in combination with intravenous AZD9150 in selected patients with MIBC who have progressed following prior therapy.
Module G: The frequency and nature of adverse events related to intravenous MEDI4736 (durvalumab) when given in combination with oral selumetinib.
Time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.
The frequency and nature of adverse events will be assessed in order to determine the safety and tolerability of MEDI 4736 (durvalumab) given intravenously in combination with selumetinib given orally to selected patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in clinical chemistry parameters.
Time frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
Changes from baseline in clinical chemistry parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in haematology parameters.
Time frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
Changes from baseline in haemotology parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in urinalysis results.
Time frame: Days 1, 8, 15, and 22 of Cycle 1, Days 1, 15, and 22 of Cycles 2 and 3 and every 4 weeks thereafter, and at discontinuation.
Changes from baseline in urinalysis findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in vital signs.
Time frame: Day 1 of Cycles 1, 2, 3, and 4 and every 4 weeks therafter, and at discontinuation.
Changes from baseline in vital signs will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in physical examination findings.
Time frame: Day 1 of Cycles 1, 2, 3, and 4 and every 4 weeks therafter, and at discontinuation.
Changes from baseline in physical examination findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in ECG findings.
Time frame: ECGs will be collected at screening, Day 1, Cycle 1and then Day 1 of each cycle from Cycle 2 onwards.
Changes from baseline in ECG findings will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in ejection fraction determined by assessing ECHO/MUGA scans.
Time frame: Ejection fraction will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.
Changes from baseline in ejection fraction determined by assessing ECHO/MUGA scans will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in coagulation parameters
Time frame: Coagulation parameters will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.
Changes from baseline in coagulation parameters will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.
All Modules: Change from baseline in lipid profile
Time frame: Lipid profile will be measured at screening, on Day 1, Cycle 1, and every 12 weeks thereafter (relative to the first dose of study drug) up to Cycle 7, and then every 16 weeks thereafter.
Changes from baseline in lipid profile will be assessed in order to determine the safety and tolerability of the drug regimen chosen in the sub study module for patients with MIBC who have progressed following prior therapy.

16 secondary outcomes

Objective response rate (ORR)
Time frame: 16 weeks and 52 weeks
Disease control rate (DCR)
Time frame: 16 weeks and 52 weeks
Progression free survival (PFS)
Time frame: up to 12 months
Duration of response (DoR)
Time frame: up to 12 months
Overall survival (OS) rate at 1 year
Time frame: 1 year
Plasma concentration of AZD4547 (Module A)
Time frame: Blood samples will be taken pre-dose on Days 1 and 8 of Cycle 1; pre-dose and 2, 3, 4 and 6 hours post-dose on Day 1 of Cycle 2; and pre-dose and 2 to 4 hours post-dose on Day 1 of Cycle 3.
Plasma concentration of MEDI4736 (durvalumab) (Module A)
Time frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and for the post-Cycle 7 8-weekly assessments, and pre-dose for Day 8 of Cycle 1.
Plasma concentration of olaparib (Module B)
Time frame: Blood samples will be taken on Day 3 of Cycles 1 and pre-dose and 4 hr post-dose. Serial samples on Day 3 of Cycle 3, pre-dose, 1, 2, 4, 6, 8, and 10 hr post-dose.
Plasma concentration of AZD1775 (Module C)
Time frame: Blood samples will be taken on Day 8 at steady state at the following time points: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hr post-dose.
Plasma concentration of MEDI4736 (durvalumab) (Module C)
Time frame: Blood samples will be taken on Days 1 and 8 of Cycle 1 pre-dose and at the end of infusion (1 hour). Samples will also be collected on Day 1 of Cycles 2 to 7 pre-dose and at the end of infusion.
Plasma concentration of MEDI4736 (durvalumab) (Module D)
Time frame: Blood samples will be taken on Days 1 and 8 of Cycle 1
Plasma concentration of vistusertib (Module E)
Time frame: Blood samples will be collected pre-dose, and 2 and 4 hr post-dose on Day 1 of Cycle 1; and pre-dose and 2 to 6 hr post-dose (matched to biopsy) on Day 2 of Cycle 2.
Plasma concentration of Medi4736 (durvalumab) (Module E).
Time frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and every 8 weeks thereafter and pre-dose for Day 8 of Cycle 1.
Plasma concentration of AZD9150 (Module F)
Time frame: Blood samples will be taken pre-dose of Days -7, -5, and -3 of the lead-in portion and thereafter prior to dosing and at the ned of infusion on Day 1 of Cycles 1, 2, 3, 4, 6, and 8 (approximately 8 months).
Plasma concentration of MEDI4736 (durvalumab) (Module F).
Time frame: Blood samples will be taken pre-dose and end of infusion for Day 1 of Cycles 1 to 7 and every 8 weeks thereafter and pre-dose for Day 8 of Cycle 1.
The presence of Anti-Drug Antibodies (ADA) and ADA neutralising antibodies to MEDI4736 will be assessed in patients receiving MEDI4736 in any sub-study module.
Time frame: Blood samples will be collected prior to MEDI4736 dosing on Day 1 of Cycles 1, 2 and 4 and every 12 weeks thereafter (up to 12 months).

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
Background: PubMed 33941921Powles T, Carroll D, Chowdhury S, Gravis G, Joly F, Carles J, Flechon A, Maroto P, Petrylak D, Rolland F, Cook N, Balar AV, Sridhar SS, Galsky MD, Grivas P, Ravaud A, Jones R, Cosaert J, Hodgson D, Kozarewa I, Mather R, McEwen R, Mercier F, Landers D. An adaptive, biomarker-directed platform study of durvalumab in combination with targeted therapies in advanced urothelial cancer. Nat Med. 2021 May;27(5):793-801. doi: 10.1038/s41591-021-01317-6. Epub 2021 May 3.
Derived from this study: PubMed 32203306Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.
Clinical Study Protocol RedactedLink provided by the sponsor.
Statistical Analysis Plan RedactedLink provided by the sponsor.
CSR Synopsis RedactedLink provided by the sponsor.
An adaptive, biomarker-directed platform study of durvalumab in combination with targeted therapies in advanced urothelial cancerLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

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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.

Thomas Powles, MBBS, MRCP, MD principal investigator

Barts Cancer Center, Barts and The London School of Medicine and Denistry

Hendrik-Tobias Arkenau, MD, PhD principal investigator

Sarah Cannon Research Institute, UK

27 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD4547, MEDI4736 and Olaparib in people with Muscle Invasive Bladder Cancer, run by AstraZeneca at 27 sites in 5 countries.

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 18 inclusion and 44 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: under way, not looking for participants, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States, France, United Kingdom, Canada, 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 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.

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?

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?

Module A: The frequency and nature of adverse events related to AZD4547 monotherapy. (time frame: Adverse events will be assessed at each clinic visit, and at study discontinuation and 90 days after the end of treatment. Clinic visits are generally scheduled weekly.). The study lists 17 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 NCT02546661, 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 1 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.