BAY 1895344 + Chemotherapy for Bladder Cancer

Recruiting at 9 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Active malignancy, Peripheral neuropathy, others

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

Compensation: Varies

Number of Visits: 7

Duration: 18 weeks

74 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are on certain medications that interact with the trial drugs. It's important to discuss your current medications with the trial team to see if any changes are needed.

What data supports the effectiveness of the drug combination BAY 1895344, Cisplatin, and Gemcitabine Hydrochloride for bladder cancer?

Research shows that the combination of gemcitabine and cisplatin is effective for advanced bladder cancer, with response rates of 41% to 57% and a favorable safety profile compared to older treatments. This suggests that combining these drugs with BAY 1895344 could potentially enhance treatment effectiveness. ^{1 2 3 4 5}

What safety data exists for BAY 1895344 + Chemotherapy for Bladder Cancer?

Cisplatin (also known as CDDP) and gemcitabine are chemotherapy drugs used in bladder cancer treatment. Cisplatin can cause side effects like nausea, vomiting, kidney damage, and blood cell issues, while gemcitabine is generally better tolerated with fewer severe side effects. The combination of gemcitabine and cisplatin has shown moderate toxicity and is considered safer than some other regimens. ^{3 5 6 7 8}

What makes the drug BAY 1895344 combined with chemotherapy unique for bladder cancer treatment?

The drug BAY 1895344 combined with chemotherapy is unique because it includes a novel agent, BAY 1895344, which is not part of the standard gemcitabine and cisplatin regimen commonly used for bladder cancer. This combination may offer a new approach by potentially enhancing the effectiveness of existing chemotherapy treatments. ^{2 3 8 9 10}

Research Team

Mamta Parikh

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Eligibility Criteria

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.

Inclusion Criteria

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

Your hemoglobin level is at least 9 grams per deciliter.

I have previously received immune checkpoint inhibitor therapy.

Exclusion Criteria

I am not on any strong medication that affects liver enzymes or can't switch to another.

I haven't had chemotherapy, radiotherapy, or targeted therapies like PARP inhibitors in the specified time before joining the study.

The doctor thinks you have less than 6 weeks to live.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cisplatin and elimusertib, or cisplatin, gemcitabine, and elimusertib in cycles

18 weeks

6 cycles, each 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 28 days after treatment completion

1 visit (in-person) at 30 days, then every 3 months

Long-term follow-up

Participants are monitored for progression-free survival and response rate

Up to 2 years

Treatment Details

Interventions

• BAY 1895344
• Cisplatin
• Gemcitabine Hydrochloride

Trial Overview 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.

Participant Groups

Group I: Arm II (cisplatin, gemcitabine, elimusertib) Experimental Treatment 3 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 Treatment 2 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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

The gemcitabine and cisplatin doublet regimen has shown a better efficacy-toxicity profile compared to the traditional MVAC chemotherapy for bladder cancer, making it a more suitable option for elderly patients with metastatic disease.

Ongoing phase II studies of triplet regimens combining gemcitabine, paclitaxel, and either cisplatin or carboplatin have demonstrated promising activity and improved median survival, particularly in patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. de Wit, R., Bellmunt, J.[2022]

The combination of paclitaxel, cisplatin, and gemcitabine demonstrated a high overall response rate of 77.6% in 61 patients with advanced transitional-cell carcinoma, indicating strong antitumor activity.

The recommended doses for further studies were established as 80 mg/m² of paclitaxel and 1,000 mg/m² of gemcitabine, with manageable toxicity, although significant side effects like grade 3 neutropenia were observed in 55% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group. Bellmunt, J., Guillem, V., Paz-Ares, L., et al.[2022]

In a phase II study involving 27 patients with advanced transitional cell carcinoma, the sequential treatment of gemcitabine and carboplatin followed by paclitaxel resulted in an objective response rate of 40.7%, with one complete response and ten partial responses.

The treatment was generally safe, with hematologic toxicities being the most common, but the study concluded that while this sequential approach appears safer than triplet therapy, it did not significantly improve patient outcomes, indicating a need for further research with larger groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. Kattan, JG., Boutros, CY., Farhat, FS., et al.[2021]

In a phase III trial with 405 patients, the gemcitabine/cisplatin (GC) regimen showed comparable effectiveness to the standard MVAC regimen for advanced bladder cancer, with similar response rates and overall survival.

The GC regimen demonstrated significantly better safety and tolerability, with much lower rates of severe side effects like mucositis and neutropenic fever, suggesting it should be preferred as the standard treatment for advanced bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in advanced bladder cancer. von der Maase, H.[2022]

In a study of 11 patients with untreated metastatic bladder cancer, cis-diamminedichloroplatinum (CDDP) showed a partial response in 37.5% of patients, indicating some efficacy in this difficult-to-treat population.

While CDDP was generally tolerated, it caused moderate nausea and vomiting in some patients, and nephrotoxicity was a significant concern, leading to renal failure in 2 patients with ureteral obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. De Lena, M., Lorusso, V., Iacobellis, U., et al.[2022]

Cis-diamminedichloroplatinum (II) demonstrated significant efficacy as a single-agent treatment for advanced genitourinary tumors, achieving complete responses in 16.7% of testicular cancer patients and partial responses in 50% of the same group, based on a study of 112 patients with various genitourinary tumors.

The treatment was associated with common adverse reactions such as gastrointestinal issues, nephrotoxicity, and myelosuppression, but also included occasional ototoxicity and peripheral neuropathies, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study of cis-diamminedichloroplatinum (II) in genitourinary cancer]. [2013]

Gemcitabine, a newer chemotherapy agent, has shown promising activity against bladder cancer, both as a single agent and in combination with cisplatin, offering a favorable toxicity profile compared to traditional treatments.

The standard treatment for advanced bladder cancer in the US remains the M-VAC regimen, but ongoing trials are exploring the effectiveness of gemcitabine combined with other agents, which may lead to improved treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. Ryan, CW., Vogelzang, NJ.[2022]

In a study of 28 patients aged 65 and older with urothelial cancer, the combination of gemcitabine and cisplatin was found to be reasonably well-tolerated, with 57.1% receiving it in the neoadjuvant setting.

The study suggests that a lower dose of gemcitabine (1000 mg/m²) is better tolerated than the standard higher dose (1250 mg/m²), as higher doses led to more hematologic toxicity and treatment delays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Gemcitabine Plus Cisplatin for Treatment of Urothelial Cancer in the Elderly Population. Jan, AS., Dolan, DE., Lombardi, K., et al.[2022]

The current chemotherapy regimen for metastatic bladder cancer, which includes cisplatin, methotrexate, vinblastine, and doxorubicin, shows limited impact on survival and is associated with significant toxicity.

Gemcitabine, a novel nucleoside analogue, has demonstrated promising response rates of up to 33% in phase II studies and is well tolerated, suggesting it may be a safer and effective alternative for treating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastatic bladder cancer: advances in treatment. Stadler, WM., Kuzel, TM., Raghavan, D., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Gemcitabine and cisplatin after radical cystectomy for bladder cancer in an adjuvant setting: feasibility study from the Genito-Urinary Group of the French Federation of Cancer Centers. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine in advanced bladder cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

[Phase II study of cis-diamminedichloroplatinum (II) in genitourinary cancer]. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Tolerability of Gemcitabine Plus Cisplatin for Treatment of Urothelial Cancer in the Elderly Population. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Metastatic bladder cancer: advances in treatment. [2022]