What side effects are associated with this type of intervention?

Common treatments for bladder cancer, such as cisplatin and gemcitabine chemotherapy, are associated with side effects like nephrotoxicity, ototoxicity, neurotoxicity, nausea, vomiting, and myelosuppression for cisplatin, and myelosuppression, flu-like symptoms, and liver enzyme abnormalities for gemcitabine. Enzyme inhibitors like BAY 1895344 may add side effects such as fatigue, gastrointestinal disturbances, and potential liver toxicity. Combining these treatments can increase both efficacy and the risk of side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for bladder cancer, including chemotherapy agents like cisplatin and gemcitabine. Cisplatin and gemcitabine are commonly used in combination for advanced urothelial carcinoma. Additionally, the FDA has approved immune checkpoint inhibitors such as pembrolizumab and atezolizumab for patients who have progressed on platinum-based chemotherapy. While enzyme inhibitors specifically combined with cisplatin and gemcitabine are still under investigation, these approvals highlight the evolving landscape of bladder cancer treatment.

What other types of research exist?

Promising novel alternatives to BAY 1895344 in combination with Cisplatin and Gemcitabine for bladder cancer patients include: <ol> <li>Atezolizumab: An immune checkpoint inhibitor that has shown efficacy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma.</li> <li></li> </ol> Enfortumab Vedotin: An antibody-drug conjugate that has demonstrated effectiveness in patients who have progressed after platinum-based chemotherapy and checkpoint inhibitors. 3. Sacituzumab Govitecan: Another antibody-drug conjugate that has shown promise in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors.

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Enzyme Inhibitor

BAY 1895344 + Chemotherapy for Bladder Cancer

Phase 1

Waitlist Available

Led By Mamta Parikh

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

Availability of archival FFPE tissue

Must not have

Must NOT have had prior treatment with ATR inhibitor (prior BAY1895344 or other investigational ATR inhibitors), or current treatment with any other investigational agents

Sensorineural hearing loss (grade 2 or higher by CTCAE)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, BAY 1895344, combined with chemotherapy to treat advanced cancers. It aims to find the best dose and check for side effects. The treatment works by blocking enzymes needed for tumor growth and killing cancer cells. The trial focuses on patients with advanced solid tumors or urothelial cancer.

Who is the study for?

Adults with advanced solid tumors or urothelial cancer, including those HIV-positive on effective therapy, and those who've had certain prior treatments. Must have adequate organ function and not be pregnant or breastfeeding. Excludes individuals with significant neuropathy, hearing loss, recent chemotherapy/radiotherapy, other active cancers needing treatment (except some skin/prostate cancers), or psychiatric/social conditions affecting compliance.

What is being tested?

The trial is testing BAY 1895344 added to usual chemotherapy drugs Cisplatin or Cisplatin plus Gemcitabine for treating advanced solid tumors. It aims to find the best dose of BAY 1895344 and assess its benefits/side effects when combined with these chemotherapies.

What are the potential side effects?

Potential side effects include reactions related to the immune system's response to the drug, nerve damage (neuropathy), hearing issues, as well as typical chemotherapy-related side effects like fatigue, nausea, blood cell count changes leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself but might not be able to do heavy physical work.

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I have a preserved tissue sample available.

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I am 18 years old or older.

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My hepatitis B is under control with treatment.

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My bladder cancer cannot be removed by surgery.

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My advanced cancer is measurable and may be treated with cisplatin.

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I have received less than 300 mg/m^2 of cisplatin.

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I had hepatitis C but have been treated and cured.

Exclusion Criteria

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

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I have not been treated with ATR inhibitors or any experimental drugs.

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I have moderate to severe hearing loss.

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I do not have severe nerve damage.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of adverse events

Secondary study objectives

ATM expression

Deoxyribonucleic acid (DNA) damage repair (DDR) mutations

PK parameter - area under the concentration-time curve (AUC)

+3 more

Side effects data

From 2012 Phase 3 trial • 256 Patients • NCT01005680

51%

Neutropenia

47%

Leukopenia

46%

Nausea

43%

Vomiting

35%

Anaemia

31%

Decreased appetite

26%

Haemoglobin decreased

26%

Fatigue

25%

Constipation

25%

White blood cell count decreased

24%

Neutrophil count decreased

19%

Alanine aminotransferase increased

13%

Platelet count decreased

12%

Rash

10%

Aspartate aminotransferase increased

10%

Thrombocytopenia

Blood sodium decreased

Hypokalaemia

Insomnia

Pyrexia

Hyponatraemia

Blood creatinine increased

Lymphopenia

Diarrhoea

Dyspepsia

Red blood cell count decreased

Cough

Dizziness

Bone marrow failure

Ischaemic stroke

Dyspnoea

Cerebral infarction

Pulmonary embolism

Embolism venous

Superior vena cava syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Gemcitabine Plus Cisplatin (GC)

Pemetrexed Plus Cisplatin (PC)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (cisplatin, gemcitabine, elimusertib)Experimental Treatment3 Interventions

Patients receive cisplatin IV over 1-2 hours on day 1 and 8, gemcitabine IV over 30 minutes on days 1 and 8, and elimusertib PO QD on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (cisplatin, elimusertib)Experimental Treatment2 Interventions

Patients receive cisplatin IV over 1-2 hours on day 1 and 8, and elimusertib PO QD on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gemcitabine Hydrochloride

2005

Completed Phase 3

~5420

Cisplatin

2013

Completed Phase 3

~3120

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Bladder cancer treatments often involve chemotherapy and enzyme inhibition. Chemotherapy drugs like cisplatin and gemcitabine work by interfering with the DNA replication process, leading to cell death. Cisplatin forms cross-links in DNA, preventing cell division, while gemcitabine incorporates into DNA, causing chain termination. Enzyme inhibitors, such as BAY 1895344, target specific enzymes necessary for cancer cell growth and survival, thereby halting tumor progression. These mechanisms are crucial for bladder cancer patients as they offer multiple avenues to disrupt cancer cell proliferation, potentially improving treatment efficacy and patient outcomes.

Targeting mTOR and p53 Signaling Inhibits Muscle Invasive Bladder Cancer In Vivo.