Cisplatin + Gemcitabine +/- Berzosertib for Bladder Cancer

No longer recruiting at 45 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of treatment with cisplatin and gemcitabine, with or without a new drug called berzosertib, for people with urothelial cancer that has spread. Cisplatin and gemcitabine are chemotherapy drugs that stop cancer cells from growing and spreading. Researchers are testing berzosertib to see if it can enhance this effect by blocking certain enzymes that aid cancer cell growth. Individuals diagnosed with metastatic urothelial cancer, who have not yet received chemotherapy for it and have measurable cancer, might be suitable for this study. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should avoid taking strong inhibitors or inducers of CYP3A4, as they may interact with the trial drugs. It's important to discuss your current medications with the study team to ensure there are no interactions.

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

Research has shown that patients generally tolerate the combination of cisplatin and gemcitabine well, meaning most people can handle it without serious issues. Studies have found this combination to be safe, with manageable side effects. For instance, one study found that this pair worked well and was tolerated by patients with various types of cancer.

Regarding berzosertib, research found that adding it to gemcitabine was also well-tolerated by patients with advanced solid tumors. This suggests that using cisplatin, gemcitabine, and berzosertib together does not cause significantly more severe side effects than using just cisplatin and gemcitabine.

Overall, treatments in this trial have been tested in other contexts and have demonstrated a reasonable safety profile based on previous research.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they introduce berzosertib to the standard chemotherapy regimen for bladder cancer. Unlike the usual treatment with just cisplatin and gemcitabine, berzosertib is an ATR kinase inhibitor that might enhance the effectiveness of chemotherapy by preventing cancer cells from repairing themselves after treatment. This unique mechanism could potentially increase the treatment's ability to stop or slow down cancer progression more effectively than current options. By combining berzosertib with traditional chemotherapy drugs, researchers are hopeful for improved outcomes for patients with bladder cancer.

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

Studies have shown that using cisplatin and gemcitabine together effectively treats advanced bladder cancer. Patients receiving this combination, one of the treatment arms in this trial, have a 41% chance of tumor reduction, with about 22% experiencing a complete response, meaning their cancer disappears. Another trial arm includes adding berzosertib to the cisplatin and gemcitabine regimen. However, research indicates that berzosertib does not significantly extend the time patients live without cancer progression or increase overall survival. In short, cisplatin and gemcitabine work well together, but berzosertib does not provide extra benefits.12467

Who Is on the Research Team?

Sumanta Kumar Pal, M.D., FASCO | City ...

Sumanta K. Pal

Principal Investigator

City of Hope Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with metastatic urothelial carcinoma, including cancers from the bladder, ureter, or upper tract. Participants must not have had chemotherapy for metastatic disease but may have had immunotherapy. They should be in good physical condition (Karnofsky >= 70%), have proper organ function, and no severe illnesses that could interfere with the study. Women of childbearing potential and men must use effective contraception during the study.

Inclusion Criteria

Life expectancy of greater than 3 months
Absolute neutrophil count >= 1,500/mcL
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
See 12 more

Exclusion Criteria

I have moderate to severe nerve pain or damage.
Patients who are receiving any other investigational agents
I am allergic to M6620, cisplatin, or gemcitabine, or similar drugs.
See 4 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive gemcitabine hydrochloride and cisplatin, with or without berzosertib, in 21-day cycles for up to 6 cycles

18 weeks
6 cycles, each with multiple visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

  • Berzosertib
  • Cisplatin
  • Gemcitabine Hydrochloride
Trial Overview The trial is testing how well cisplatin and gemcitabine hydrochloride work alone compared to when combined with berzosertib in treating metastatic urothelial cancer. Cisplatin and gemcitabine are chemotherapy drugs; berzosertib blocks enzymes needed by cancer cells to grow.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Arm B (gemcitabine hydrochloride, cisplatin)Experimental Treatment2 Interventions
Group II: Arm A (berzosertib, gemcitabine hydrochloride, cisplatin)Experimental Treatment3 Interventions

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

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Approved in European Union as Platinol for:
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Approved in United States as Platinol for:
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Approved in Canada as Platinol for:
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Approved in Japan as Platinol for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/34436521/
Effect of Cisplatin and Gemcitabine With or Without ... - PubMedThe addition of berzosertib to cisplatin with gemcitabine did not prolong progression-free survival relative to cisplatin with gemcitabine alone.
Effect of Cisplatin and Gemcitabine With or Without ...The findings of this trial indicate that the addition of berzosertib does not add to the efficacy of cisplatin and gemcitabine chemotherapy in patients with ...
Study Details | NCT02567409 | Cisplatin and Gemcitabine ...This phase II trial studies how well cisplatin and gemcitabine hydrochloride with or without berzosertib works in treating patients with urothelial cancer ...
A randomized phase II study comparing cisplatin and ...The current study sought to determine if the combination of berzosertib and CG could improve clinical outcomes in mUC.
Extended follow-up report of a randomized phase II trial ...Conclusions: With >18 months of extended follow-up, there remained no PFS or OS benefit with the addition of berzosertib to GC, compared to GC ...
Phase 1 study of the ATR inhibitor berzosertib (formerly ...Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs.
Effect of Cisplatin and Gemcitabine With or Without ...Median overall survival was shorter with cisplatin with gemcitabine plus berzosertib compared with cisplatin with gemcitabine alone (14.4 vs ...
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