Chemotherapy Combination for Bladder Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 21 days per cycle

46 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, gemcitabine, and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving fluorouracil together with leucovorin, gemcitabine, and cisplatin works in treating patients with metastatic or unresectable adenocarcinoma of the urothelium or urachal remnant (part of the bladder).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the chemotherapy drug combination for bladder cancer?

Research shows that chemotherapy combinations, including drugs like cisplatin and 5-fluorouracil, can lead to significant tumor regression in advanced bladder cancer, with some studies reporting a 70% response rate. These combinations are more effective than single drugs, although they can have substantial side effects. ^{1 2 3 4 5}

Is the chemotherapy combination of gemcitabine, cisplatin, 5-fluorouracil, and leucovorin generally safe for humans?

The combination of gemcitabine and cisplatin has shown moderate toxicity in bladder cancer patients, and a regimen including cisplatin, 5-fluorouracil, and leucovorin has been reported to have low toxicity. These treatments have been evaluated for safety in patients with advanced urothelial carcinoma. ^{6 7 8 9 10}

What makes the chemotherapy combination for bladder cancer unique?

This treatment combines 5-Fluorouracil (5-FU) with Leucovorin to enhance the effectiveness of 5-FU, along with Cisplatin and Gemcitabine, which are known to be active against bladder cancer. This combination aims to improve response rates and overcome resistance seen in standard treatments, offering a potentially more effective option for patients who have not responded to other therapies. ^{1 2 11 12 13}

Research Team

Arlene Siefker-Radtke, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced or inoperable adenocarcinoma of the urothelium or urachal remnant, who understand the study's experimental nature. They should have a life expectancy over 9 months, decent physical function (Zubrod PS ≤2), and adequate organ function. Pregnant women, those with mental disabilities unable to consent, uncontrolled brain metastases, or other life-threatening illnesses are excluded.

Inclusion Criteria

My overall health is good enough for treatment, including my blood, liver, and kidney functions.

My cancer can be measured in two ways and meets size requirements.

My heart is functioning well despite my history of heart issues.

Exclusion Criteria

My brain metastases are not under control.

My cancer started outside the urinary tract and has spread to my bladder.

I do not have a severe illness that would stop me from completing the treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fluorouracil, leucovorin, gemcitabine, and cisplatin. Treatment is administered in 21-day cycles with continuous infusion of 5-FU, daily leucovorin and cisplatin, and gemcitabine on days 1 and 5.

21 days per cycle

5 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3-6 months.

Every 3-6 months

Treatment Details

Interventions

• 5-Fluorouracil (5-FU)
• Cisplatin
• Gemcitabine
• Leucovorin

Trial Overview The trial tests a combination chemotherapy regimen using fluorouracil (5-FU), leucovorin, gemcitabine, and cisplatin on patients with metastatic or unresectable bladder-related cancers. It aims to see how well these drugs work together to stop cancer cells from growing by attacking them in different ways.

Participant Groups

Group I: 5-FU, Leucovorin, Gemcitabine + Cisplatin Experimental Treatment 4 Interventions

5-FU continuous infusion over Days 1 - 5; Leucovorin once a day as a short infusion on Days 1 - 5; Cisplatin infusion over a few hours (usually 2-4 hours) once a day on Days 1 - 5; Gemcitabine infusion over 30 minutes on Days 1 \& 5 only.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Standard chemotherapy for transitional cell carcinoma of the bladder, known as MVAC (cisplatin, methotrexate, vinblastine, and doxorubicin), shows a high response rate but rarely leads to long-term survival, indicating a need for more effective and less toxic treatments.

Alternative agents like paclitaxel, gemcitabine, and gallium nitrate have demonstrated significant activity, either alone or in combination with cisplatin or carboplatin, achieving response rates of 40% to 70% in patients with advanced disease, although the best treatment regimen is still not established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current chemotherapy of locally advanced or metastatic bladder tumors]. Dourthe, LM., Ceccaldi, B., Fournier, R., et al.[2006]

Recent phase II clinical trials have shown that combination therapies using cis-diamminedichloride platinum II, Adriamycin, and methotrexate are effective in treating advanced transitional cell carcinoma of the urothelial tract.

While combination regimens appear to lead to higher remission rates compared to single-agent treatments, further prospective randomized trials are necessary to confirm these benefits and address challenges in patient selection and response criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of Metastatic Bladder Cancer. Yagoda, A.[2019]

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]

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 33 patients with advanced urothelial carcinoma who had previously failed M-VAC chemotherapy, the combination of gemcitabine and cisplatin (GC) resulted in an overall response rate of 39.4%, with 6% achieving complete responses and 33.3% partial responses.

Despite significant side effects like grade 3-4 neutropenia in 66.7% of patients, there were no fatal side effects, suggesting that GC chemotherapy is a feasible option that may offer a survival benefit, with a mean survival time of 10.5 months after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of gemcitabine plus cisplatin regimen for patients with advanced urothelial carcinoma after failure of M-VAC regimen. Gondo, T., Ohori, M., Hamada, R., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

[Current chemotherapy of locally advanced or metastatic bladder tumors]. [2006]

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

Chemotherapy of Metastatic Bladder Cancer. [2019]

3. Japan pubmed.ncbi.nlm.nih.gov

[Sequential methotrexate and 5-fluorouracil, doxorubicin, and cisplatin for advanced urothelial cancer]. [2019]

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

Advanced transitional cell bladder cancer: a treatable disease. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

[Chemotherapy for urothelial cancer of the bladder--update 2012]. [2012]

6. Australia pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Gemcitabine and cisplatin therapy in advanced or metastatic urothelial cancer: comparison of side effect with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin)]. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

The efficacy and safety of gemcitabine plus cisplatin regimen for patients with advanced urothelial carcinoma after failure of M-VAC regimen. [2022]

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

Phase II trial of weekly paclitaxel, cisplatin plus infusional high dose 5-fluorouracil and leucovorin for metastatic urothelial carcinoma. [2015]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Results of systemic chemotherapy of advanced bladder carcinomas (phase II study). [2019]

12. England pubmed.ncbi.nlm.nih.gov

A phase II study of 5-fluorouracil and high dose folinic acid in cisplatin-refractory metastatic bladder cancer. [2020]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy with sequential methotrexate and 5-fluorouracil scheduling, epirubicin and cisplatin for locally advanced bladder cancer. [2017]