Multiple Drugs for Bladder Cancer

(BISCAY Trial)

Not currently recruiting at 26 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Must not be taking: Immunosuppressives, CYP3A4 inhibitors

Disqualifiers: Autoimmune disease, IBD, severe disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 94

Duration: up to 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for people with muscle invasive bladder cancer (MIBC) that has not responded to previous treatments. Researchers aim to assess the safety and effectiveness of different drug combinations against this type of cancer. The trial consists of several parts, each testing different drug combinations, including AZD1775, AZD4547, AZD9150, MEDI4736, Olaparib (Lynparza), Selumetinib (Koselugo), and Vistusertib, to identify the best approach. People with MIBC that has spread, who have tried other treatments without success, might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive potentially groundbreaking therapies.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must not have had immunotherapy, chemotherapy, anticancer agents, or radiotherapy within 4 weeks, and you cannot be on concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy. Additionally, certain modules have specific restrictions on medications that affect liver enzymes or are used for other treatments.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In previous studies, AZD4547 has shown common side effects, such as tiredness, constipation, and diarrhea, affecting about 27% to 47% of patients. While most people handle it well, some may experience these issues. Research indicates that MEDI4736 (also known as durvalumab) is generally safe for many patients, though some might feel tired or have itchy skin.

The safety of using AZD4547 and MEDI4736 together is still under study. Early results suggest the combination is manageable, but more information is needed for confirmation.

For MEDI4736 combined with Olaparib, early findings suggest that most people tolerate the combination well, without serious problems.

The combination of MEDI4736 and AZD1775 has shown a good safety profile in early studies, indicating that side effects are not too severe for most people.

When MEDI4736 is paired with Vistusertib, the combination seems safe for patients with several types of cancer. However, more detailed information on specific side effects is still being collected.

The duo of MEDI4736 and AZD9150 is also under study. So far, it appears safe, but more research is needed to confirm this.

Lastly, the combination of MEDI4736 and Selumetinib is being tested for safety. Early data suggest it is safe for most patients, but further research will help confirm this.

As this is a Phase 1 trial, the main goal is to learn about safety and how well these treatments are tolerated. This phase usually involves fewer participants to closely monitor safety before larger trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they explore innovative combinations and mechanisms. Unlike the typical chemotherapy and immunotherapy options, these investigational drugs, like AZD4547 and Olaparib, target specific pathways in cancer cells, potentially leading to more effective and personalized treatments. MEDI4736 (durvalumab) is combined in different ways with drugs like AZD1775 and Vistusertib to enhance immune response and inhibit cancer growth. These novel approaches could offer new hope for patients, especially those who haven't had success with standard treatments.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that the drug AZD4547, which participants in this trial may receive, effectively treats bladder cancer, with two out of three patients in a study responding well. In this trial, some participants will receive MEDI4736 (durvalumab) alone, which studies indicate is safe and effective for treating advanced bladder cancer. Other participants will receive combinations of MEDI4736 with different drugs. For instance, combining MEDI4736 with AZD4547 does not improve results compared to using AZD4547 alone. However, combining MEDI4736 with Olaparib appears effective and is generally well-tolerated. Additionally, using MEDI4736 with AZD1775 has shown good safety and effectiveness. Overall, MEDI4736, whether used alone or with other drugs, shows promise in managing bladder cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Hendrik-Tobias Arkenau, MD

Principal Investigator

Sarah Cannon Research Institute, UK

Thomas Powles, MBBS, MRCP, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

WHO perf. status 0-1

Hgb ≥10 g/dL

Exclusion Criteria

You have been diagnosed with an autoimmune disease, inflammatory bowel disease (IBD), primary immunodeficiency, or have had an organ transplant that requires medication to suppress your immune system within the past two years.

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

My brain or spinal cancer is stable and I haven't needed steroids for 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various combinations of MEDI4736 and other agents based on genomic alterations in a modular design

up to 12 months

Weekly visits for adverse event assessment and every 4 weeks for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days post-treatment

Visits at study discontinuation and 90 days after end of treatment

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if they benefit from the therapy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AZD1775
• AZD4547
• AZD9150
• MEDI4736
• Olaparib
• Selumetinib
• Vistusertib

Trial Overview

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.

How Is the Trial Designed?

Group I: Module G: MEDI4736 + Selumetinib Experimental Treatment 2 Interventions

Group II: Module F: MEDI4736 (durvaluamb) + AZD9150 Experimental Treatment 2 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) + Vistusertib Experimental Treatment 2 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) monotherapy Experimental Treatment 1 Intervention

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

Group V: Module C: MEDI4736 (durvaluamb) + AZD1775 Experimental Treatment 2 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) + Olaparib Experimental Treatment 2 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) + AZD4547 Experimental Treatment 2 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 Monotherapy Experimental Treatment 1 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.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Neoadjuvant chemotherapy has been shown to improve overall survival in patients with locally advanced muscle-invasive bladder cancer, but its use in clinical practice remains low due to ongoing controversies regarding adjuvant chemotherapy.

Recent advancements include the approval of atezolizumab, a checkpoint inhibitor, for metastatic bladder cancer, alongside other promising therapies targeting mutational signatures, such as VEGF and HER2-directed agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises. Aragon-Ching, JB., Trump, DL.[2017]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

The gemcitabine and cisplatin (CG) combination has emerged as the new standard of care for metastatic bladder carcinoma, showing similar effectiveness to the previous standard M-VAC regimen but with less toxicity.

Novel treatments like pemetrexed and vinflunine are showing promise in clinical trials, with pemetrexed demonstrating a 28% response rate and vinflunine providing an 18% response rate in pretreated patients, indicating potential for improved outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of metastatic bladder carcinoma. Iaffaioli, RV., Milano, A., Caponigro, F.[2020]

Cisplatin and gemcitabine are the most commonly used first-line treatment for advanced bladder cancer, showing comparable efficacy and better tolerance than the traditional four-drug regimen, especially for patients who cannot receive cisplatin due to comorbidities.

Recent advancements in molecular characterization of advanced bladder cancer have revealed actionable genetic alterations, leading to the development of targeted therapies that may significantly improve treatment outcomes by matching specific mutations with appropriate treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of genomics in the management of advanced bladder cancer. Guancial, EA., Rosenberg, JE.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7367548/

Results From the NCI-MATCH Trial (EAY131) Subprotocol W

Stable disease was observed in 37.5% (90% CI, 25.8% to 50.4%). The median progression-free survival (PFS) was 3.4 months, and the 6-month PFS rate was 15% (90% ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5502072/

Safety, tolerability and pharmacokinetics of the fibroblast ...

These data suggest a potential association between FGFR amplification status and clinical benefit with AZD4547 therapy.

3.

urotoday.com

urotoday.com/clinical-trials/from-the-editor/100442-from-the-desk-of-evan-yu-fibroblast-growth-factor-receptors-a-new-hope-for-patients-with-urothelial-carcinomas.html

Fibroblast Growth Factor Receptors, a New Hope for ...

AZD4547 has shown activity in urothelial bladder cancer in a trial where FGFR alteration was required. Specifically, 2 of 3 patients showed ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.4521

FIESTA: A phase Ib and pharmacokinetic trial of AZD4547 ...

There were no treatment-related deaths or serious treatment-emergent adverse events. One dose-limiting toxicity was seen at 80mg BD of AZD4547 ( ...

5.

aging-us.com

aging-us.com/article/102286/text

Sulfated polysaccharide of Sepiella maindroni ink targets ...

These results indicate that combination therapy decreased bladder cancer cell migration and promoted cell cycle arrest and apoptosis to a larger extent than ...

6.

sciencedirect.com

sciencedirect.com/topics/medicine-and-dentistry/azd-4547

Azd 4547 - an overview | ScienceDirect Topics

Common AEs of AZD4547 alone or in combination included fatigue (≈47%), constipation (33–47%), dry skin (33–42%) and diarrhea (27%). PFS and OS at 6 months with ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.789

Efficacy and safety of fexagratinib (Fexa) in combination ...

Fexagratinib(former AZD4547)is a potent and selective inhibitor of FGFR and had showed promising anti-tumor activity in mUC pts with FGFRa. This ...

8.

mycancergenome.org

mycancergenome.org/content/clinical_trials/NCT02546661/

Clinical Trial: NCT02546661

Module A includes an AZD4547 monotherapy arm and a MEDI4736 (durvalumab) + AZD4547 combination therapy arm and will investigate the safety ...