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Wee1 Inhibitor

Multiple Drugs for Bladder Cancer (BISCAY Trial)

Phase 1

Waitlist Available

Led By Thomas Powles, MBBS, MRCP, MD

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

2nd/3rd line

Confirmation of FGFR3 mutation or FGFR fusion

Must not have

Immunosuppressive drugs <28 days

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is for patients with bladder cancer who have progressed on prior treatment. It is designed to study the safety and tolerability of multiple agents as monotherapy or in combination.

Who is the study for?

This trial is for adults over 25 with muscle invasive bladder cancer who've had prior treatment fail within a year. They must have at least one measurable lesion, be in good physical condition (WHO performance status 0-1), and not have certain genetic mutations or severe organ dysfunction. Participants need to use effective contraception during and after the study for specified periods.

What is being tested?

The trial tests multiple drugs (MEDI4736, Olaparib, AZD1775, etc.) alone or in combination against bladder cancer. It's an early-phase study assessing safety, tolerability, how the body processes these drugs, and their effectiveness against tumors.

What are the potential side effects?

Potential side effects include immune system reactions that can cause inflammation in various organs; blood disorders; fatigue; digestive issues like nausea or diarrhea; increased risk of infections due to lowered immunity; possible liver function changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My treatment is in the 2nd or 3rd round.

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My cancer has a FGFR3 mutation or fusion.

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My blood tests show normal white blood cells, neutrophils, and platelets.

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My tumor has specific genetic changes.

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My bladder cancer has spread to other parts of my body.

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I am 25 years old or older.

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My cancer has a harmful change in DNA repair genes.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't taken immunosuppressive drugs in the last 28 days.

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I have heart issues or uncontrolled blood pressure.

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I have been treated with a PARP inhibitor like olaparib before.

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I have a history of myelodysplastic syndrome or acute myeloid leukemia.

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I have ongoing issues with nausea, vomiting, or have had part of my bowel removed.

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I am not taking medication that interacts with CYP3A4 enzymes.

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I am currently using herbal supplements.

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I haven't taken any blood cell growth factors in the last 14 days.

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I have ongoing nausea or a long-term stomach/intestine condition.

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I have not had heart disease in the last 6 months.

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I have not taken any mTOR inhibitor medications.

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I have kidney disease or a condition affecting my kidney's acid levels.

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I have had eye problems like retinal issues or high eye pressure.

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I have a history of lung conditions that needed steroid treatment.

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I had major surgery less than 4 weeks ago.

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I do not have any severe or uncontrolled illnesses.

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I am not taking strong medication that affects liver enzymes.

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My diabetes is not well-managed.

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I still have side effects from previous cancer treatments.

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I have been treated with a MEK, Ras, or Raf inhibitor before.

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I have not had minor surgery within the last 14 days.

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I had a heart condition where my heart's pumping ability was reduced but have since recovered.

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I am not currently on chemotherapy, immunotherapy, biologic, or hormonal therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

All Modules: Change from baseline in ECG findings.

All Modules: Change from baseline in clinical chemistry parameters.

All Modules: Change from baseline in coagulation parameters

+14 more

Secondary study objectives

Disease control rate (DCR)

Duration of response (DoR)

Objective response rate (ORR)

+13 more

Other study objectives

Biomarker Analysis of Blood and Tissue

Correlation of biomarkers to response and/or development of cancer

Estimate overall survival (OS)

+2 more

Side effects data

From 2023 Phase 3 trial • 713 Patients • NCT02125461

36%

Cough

24%

Fatigue

22%

Dyspnoea

18%

Diarrhoea

17%

Arthralgia

17%

Radiation pneumonitis

15%

Pyrexia

15%

Decreased appetite

14%

Nausea

13%

Pruritus

13%

Rash

12%

Upper respiratory tract infection

12%

Constipation

11%

Asthenia

11%

Hypothyroidism

11%

Headache

11%

Back pain

10%

Productive cough

10%

Pneumonia

Pneumonitis

Nasopharyngitis

Insomnia

Musculoskeletal pain

Vomiting

Oedema peripheral

Myalgia

Dry skin

Hyperthyroidism

Anaemia

Bronchitis

Dizziness

Non-cardiac chest pain

Pain in extremity

Urinary tract infection

Hypertension

Hypokalaemia

Paraesthesia

Musculoskeletal chest pain

Lung infection

Atrial fibrillation

Myocardial infarction

Cardiac failure congestive

Sepsis

Herpes zoster

Chronic obstructive pulmonary disease

Acute kidney injury

100%

80%

60%

40%

20%

Study treatment Arm

Durvalumab (MEDI4736)

Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

8Treatment groups

Experimental Treatment

Group I: Module G: MEDI4736 + SelumetinibExperimental Treatment2 Interventions

Group II: Module F: MEDI4736 (durvaluamb) + AZD9150Experimental Treatment2 Interventions

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.

Group III: Module E: MEDI4736 (durvalumab) + VistusertibExperimental Treatment2 Interventions

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).

Group IV: Module D: MEDI4736 (durvalumab) monotherapyExperimental Treatment1 Intervention

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

Group V: Module C: MEDI4736 (durvaluamb) + AZD1775Experimental Treatment2 Interventions

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.

Group VI: Module B: MEDI4736 (durvalumab) + OlaparibExperimental Treatment2 Interventions

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

Group VII: Module A: MEDI4736 (durvalumab) + AZD4547Experimental Treatment2 Interventions

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

Group VIII: Module A: AZD4547 MonotherapyExperimental Treatment1 Intervention

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

MEDI4736

2016

Completed Phase 3

~5560

Olaparib

2007

Completed Phase 4

~2190