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Otwarte, randomizowane, wielolekowe, ukierunkowane na biomarkery badanie fazy 1b u pacjentów z inwazyjnym rakiem pęcherza moczowego (BISCAY)

30 września 2026 zaktualizowane przez: AstraZeneca

Otwarte, randomizowane, wieloośrodkowe, wieloośrodkowe, wieloramienne, wielolekowe, wieloramienne badanie fazy 1b z udziałem pacjentów z inwazyjnym rakiem pęcherza moczowego (MIBC), u których nastąpiła progresja choroby podczas wcześniejszego leczenia (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.

Przegląd badań

Status

Aktywny, nie rekrutujący

Warunki

Interwencja / Leczenie

Szczegółowy opis

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 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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

117

Faza

  • Faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Francja
      • Bordeaux, Francja, 33075
        • Research Site
      • Caen, Francja, 14000
        • Research Site
      • Lyon, Francja, 69373
        • Research Site
      • Marseille, Francja, 13273
        • Research Site
      • Saint-Herblain, Francja, 44805
        • Research Site
      • Toulouse, Francja, 31100
        • Research Site
  • Hiszpania
      • Badalona, Hiszpania, 08003
        • Research Site
      • Barcelona, Hiszpania, 08035
        • Research Site
      • Barcelona, Hiszpania, 08041
        • Research Site
      • Madrid, Hiszpania, 28040
        • Research Site
  • Kanada
    • Alberta
      • Edmonton, Alberta, Kanada, T6G 1Z2
        • Research Site
    • British Columbia
      • Vancouver, British Columbia, Kanada, V5Z 4E6
        • Research Site
    • Ontario
      • Toronto, Ontario, Kanada, M5G 2M9
        • Research Site
    • Quebec
      • Montreal, Quebec, Kanada, H3T 1E2
        • Research Site
  • Stany Zjednoczone
    • California
      • Los Angeles, California, Stany Zjednoczone, 90095
        • Research Site
    • Connecticut
      • New Haven, Connecticut, Stany Zjednoczone, 06510
        • Research Site
    • Florida
      • Fort Myers, Florida, Stany Zjednoczone, 33901
        • Research Site
    • New York
      • New York, New York, Stany Zjednoczone, 10032
        • Research Site
      • New York, New York, Stany Zjednoczone, 10029
        • Research Site
      • New York, New York, Stany Zjednoczone, 10116
        • Research Site
    • Ohio
      • Cleveland, Ohio, Stany Zjednoczone, 44195
        • Research Site
    • Tennessee
      • Nashville, Tennessee, Stany Zjednoczone, 37203
        • Research Site
  • Zjednoczone Królestwo
      • Glasgow, Zjednoczone Królestwo, G12 0YN
        • Research Site
      • London, Zjednoczone Królestwo, W1G 6AD
        • Research Site
      • London, Zjednoczone Królestwo, EC1M 6BQ
        • Research Site
      • Manchester, Zjednoczone Królestwo, M20 4BX
        • Research Site
      • Southampton, Zjednoczone Królestwo, SO16 6YD
        • Research Site

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat do 130 lat (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

Inclusion Criteria for all Modules:

  1. Metastatic MIBC
  2. 2nd/3rd line
  3. Failed adjuvant/neo-adjuvant chemotherapy <1 yr
  4. 1 lesion ≥10 mm at baseline in the longest diameter suitable for accurate repeated measurement
  5. WHO perf. status 0-1

For Module A:

  1. M/F ≥25
  2. Confirmation of FGFR3 mutation or FGFR fusion

For Module B:

  1. Hgb ≥10 g/dL
  2. 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:

  1. Adequate organ and marrow function, defined as Leukocytes ≥3.0x10(exp9)/L; ANC ≥1.5x10(exp9)/L; platelets ≥100x10(exp9)/L
  2. Contraceptive measures must be sustained throughout treatment with AZD9150 and for 180 days after the last dose.

Exclusion Criteria for all Modules:

  1. Immunotherapy, chemotherapy, anticancer agents, radiotherapy <4 weeks, or radiotherapy for palliation <2 weeks, any study drugs <30 days.
  2. Major surgery <4 weeks
  3. Unresolved toxicities from prior therapy
  4. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy
  5. Immunosuppressive drugs <28 days
  6. Any of the following: Autoimmune disease ≤2 yr; IBD; primary immunodeficiency; organ transplant requiring immunosuppressives
  7. Spinal cord compression or brain metastases, treated and stable & not requiring steroids for at least 4 weeks
  8. Severe or uncontrolled systemic disease
  9. 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
  10. 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
  11. 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.
  12. Live attenuated vaccination <30 days

For Module A:

  1. 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
  2. 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
  3. Refractory nausea/vomiting, chronic GI diseases, or previous bowel resection

For Module B:

  1. Transfusion <120 days
  2. Concurrent medications that are strong inhibitors of cytochrome P450 (CYP) 3A (CYP3A) or strong inducers of CYP3A4.
  3. Previous treatment with PARP inhibitor, including olaparib
  4. Patients with history of MDS or AML

For Module C:

  1. 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
  2. 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
  3. Herbal preparations
  4. Refractory nausea and vomiting or chronic GI diseases
  5. Cardiac disease <6 months

For Module E:

  1. Minor surgery <14 days of first dose
  2. 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
  3. Haemopoietic growth factors (filgrastim, sargramostim, GM-CSF) <14 days prior to treatment
  4. Other mTOR inhibitors
  5. Renal disease or renal tubular acidosis
  6. Uncontrolled Type 1 or 2 diabetes

For Module F:

1. AST ≤ 2.5xULN or ≤5xULN with liver metastases

For Module G:

  1. Have had prior treatment with a MEK, Ras or Raf inhibitor.
  2. 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)
  3. 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.
  4. Previous moderate or severe impairment of LVEF (<45% on echocardiography or equivalent on MUGA) even if full recovery has occurred.
  5. 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.
  6. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
  7. Receiving or have received systemic therapy with nitrosoureas, mitomycin or suramin within 6 weeks prior to starting study treatment.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Moduł G: MEDI4736 + selumetynib
Lek: MEDI4736

MEDI4736

Inne nazwy:
  • Durwalumab
Lek: Selumetinib

MEDI4736 (durvalumab) + Selumetinib
Eksperymentalny: Module A: AZD4547 Monotherapy

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.
Lek: AZD4547

AZD4547 Monotherapy vs. MEDI4736 (durvalumab) + AZD4547 1:1 Randomization.
Eksperymentalny: Module A: MEDI4736 (durvalumab) + AZD4547

AZD4547 will be given orally twice daily until disease progression. Patients will also receive MEDI 4736 (durvalumab) by IV infusion once every 4 weeks.
Lek: AZD4547

AZD4547 Monotherapy vs. MEDI4736 (durvalumab) + AZD4547 1:1 Randomization.

Lek: MEDI4736

MEDI4736

Inne nazwy:
  • Durwalumab
Eksperymentalny: Module B: MEDI4736 (durvalumab) + Olaparib

MEDI4736 (durvalumab) will be given by IV infusion once every 4 weeks. Olaparib will be given orally twice daily.
Lek: MEDI4736

MEDI4736

Inne nazwy:
  • Durwalumab
Lek: Olaparib

MEDI4736 (durvalumab) + Olaparib

Inne nazwy:
  • Lynparza
Eksperymentalny: Module C: MEDI4736 (durvaluamb) + AZD1775

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.
Lek: MEDI4736

MEDI4736

Inne nazwy:
  • Durwalumab
Lek: AZD1775

MEDI4736 (durvalumab) + AZD1775
Eksperymentalny: Module D: MEDI4736 (durvalumab) monotherapy

MEDI 4736 (durvalumab) will be given by IV infusion once every 4 weeks.
Lek: MEDI4736

MEDI4736

Inne nazwy:
  • Durwalumab
Eksperymentalny: Module E: MEDI4736 (durvalumab) + Vistusertib

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).
Lek: MEDI4736

MEDI4736

Inne nazwy:
  • Durwalumab
Lek: Vistusertib

MEDI4736 (durvalumab) + Vistusertib
Eksperymentalny: Module F: MEDI4736 (durvaluamb) + AZD9150

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.
Lek: MEDI4736

MEDI4736

Inne nazwy:
  • Durwalumab
Lek: AZD9150

MEDI4736 (durvalumab) + AZD9150

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Module A: The frequency and nature of adverse events related to AZD4547 monotherapy.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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.
Ramy czasowe: 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.
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
Ramy czasowe: 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.
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
Ramy czasowe: 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.
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.

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Objective response rate (ORR)
Ramy czasowe: 16 weeks and 52 weeks

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.
16 weeks and 52 weeks
Disease control rate (DCR)
Ramy czasowe: 16 weeks and 52 weeks

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
16 weeks and 52 weeks
Progression free survival (PFS)
Ramy czasowe: up to 12 months

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.
up to 12 months
Duration of response (DoR)
Ramy czasowe: up to 12 months

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.
up to 12 months
Overall survival (OS) rate at 1 year
Ramy czasowe: 1 year

Defined as the proportion of patients surviving after 1 year from the start of treatment.
1 year
Plasma concentration of AZD4547 (Module A)
Ramy czasowe: 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.

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.
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)
Ramy czasowe: 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.

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.
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)
Ramy czasowe: 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.

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.
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)
Ramy czasowe: 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.

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.
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)
Ramy czasowe: 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.

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.
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)
Ramy czasowe: Blood samples will be taken on Days 1 and 8 of Cycle 1

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.
Blood samples will be taken on Days 1 and 8 of Cycle 1
Plasma concentration of vistusertib (Module E)
Ramy czasowe: 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.

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.
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).
Ramy czasowe: 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 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.
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)
Ramy czasowe: 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).

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.
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).
Ramy czasowe: 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 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.
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.
Ramy czasowe: 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).

The formation of anti-drug antibodies and neutralizing antibodies will be assessed by validated methods.
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).

Inne miary wyników

Miara wyniku
Opis środka
Ramy czasowe
Mutation status of cancer associated genes in circulating tumour DNA (ctDNA).
Ramy czasowe: Blood samples for assessment of ctDNA will be collected at screening, on Day 1 of Cycles 1, 2, 3, and 4 (up to 91 days) and at disease progression.

Plasma and serum samples will be collected and assessed for circulating tumour DNA to explore the mutation status of cancer associated genes.
Blood samples for assessment of ctDNA will be collected at screening, on Day 1 of Cycles 1, 2, 3, and 4 (up to 91 days) and at disease progression.
Biomarker Analysis of Blood and Tissue
Ramy czasowe: Up to 12 months

Biomarker analysis of blood and tissue to assess exploratory markers, which may include but is not limited to:

  • immune cell gene expression profiles and cytokine profiles within the peripheral and tumoural compartments,
  • the presence of IFN-γ, tumour necrosis factor-α, IL-2, IL-6, IL-10, IL-8, and IL-12 as well as antibodies against tumour, self, or viral antigens,
  • expression of PD-L1,
  • CD8 and the number and phenotype of immune cells such as T-cells.

Markers relevant to the targeted therapy, for example FGFR and ligand expression and PD markers, for example pErk, pS6 and γH2AX will also be measured in tumour paired biopsy samples.

Biomarker assessments that may have the potential to identify patients likely to respond to treatment with the agents studied in this modular protocol will be investigated to determine a patient's biomarker status and for possible correlation with efficacy endpoints.
Up to 12 months
Correlation of biomarkers to response and/or development of cancer
Ramy czasowe: Throught out study (up to 18 months)

To explore potential biomarkers in residual biological samples (e.g., tumour, plasma and/or serum) which may influence development of cancer (and associated clinical characteristics) and/or response.
Throught out study (up to 18 months)
Estimate overall survival (OS)
Ramy czasowe: Up to 18 months

To estimate the overall survival for patients have been pre-screened but do not enter the main part of the study.
Up to 18 months
Objective Response Rate (ORR) (by modified RECIST 1.1)
Ramy czasowe: 16 weeks and 52 weeks

The percentage of patients who have a confirmed response of CR or PR as assessed by the investigator using a modified RECIST 1.1. Modified RECIST 1.1 will be used for patients receiving MEDI4736 because of response may occur after progression has been initially determined. Patients receiving MEDI4736 may continue to receive treatment and be followed after an initial assessment of progression until subsequent confirmation. Confirmed progression is defined as ≥20% increase in sum of diameters of target lesions compared to the nadir at 2 consecutive visits; and/or significant progression (worsening) of non-target lesions (NTLs) or new lesions (NLs) at the confirmatory scan; and/or new unequivocal lesions at the confirmatory scan. If progression is not confirmed then the visit response is assessed as SD/PR or CR and the patient should continue scheduled scans. If progression is confirmed the visit response should be assessed as progressive disease.
16 weeks and 52 weeks

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

AstraZeneca

Śledczy

  • Główny śledczy: Thomas Powles, MBBS, MRCP, MD, Barts Cancer Center, Barts and The London School of Medicine and Denistry
  • Główny śledczy: Hendrik-Tobias Arkenau, MD, PhD, Sarah Cannon Research Institute, UK

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Przydatne linki

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

28 grudnia 2016

Zakończenie podstawowe (Rzeczywisty)

18 marca 2020

Ukończenie studiów (Szacowany)

30 listopada 2026

Daty rejestracji na studia

Pierwszy przesłany

27 sierpnia 2015

Pierwszy przesłany, który spełnia kryteria kontroli jakości

9 września 2015

Pierwszy wysłany (Szacowany)

11 września 2015

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

1 października 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

30 września 2026

Ostatnia weryfikacja

1 września 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • D2615C00001
  • GU 118 (Inny identyfikator: Sarah Cannon Development Innovations, LLC)
  • BISCAY (Inny identyfikator: Sponsor)
  • 2015-002228-25 (Numer EudraCT)
  • 2015 (Grant/umowa NIH USA)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

TAK

Opis planu IPD

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.

Ramy czasowe udostępniania IPD

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Kryteria dostępu do udostępniania IPD

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Tak

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

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