Chemotherapy Combination for Bladder Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Psychosis, Life-threatening illness, Pregnancy, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy drugs to evaluate their effectiveness in treating bladder cancer that has spread or cannot be surgically removed. Researchers aim to determine if using drugs like fluorouracil (5-FU), leucovorin, gemcitabine, and cisplatin together can more effectively inhibit cancer cell growth. This trial suits individuals with bladder cancer originating in the urinary tract who have been diagnosed with metastatic cancer or have tumors that cannot be surgically removed. Participants should have measurable tumors or meet specific blood test criteria. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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.

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

Research has shown that the combination of 5-Fluorouracil (5-FU), leucovorin, gemcitabine, and cisplatin is generally well-tolerated by patients. Studies have found that most people can handle the side effects without serious issues. Common side effects include nausea, tiredness, and low blood counts, but these are usually manageable.

Although no severe reactions have been reported, individual experiences can vary. Prospective clinical trial participants should discuss potential risks with their doctor to understand what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this chemotherapy combination for bladder cancer because it integrates several potent agents in a unique regimen. Unlike standard treatments, which often involve single agents or different sequencing, this regimen delivers 5-Fluorouracil (5-FU) continuously over five days, allowing for sustained exposure to the cancer cells. It also uses Leucovorin to enhance the effectiveness of 5-FU, while combining it with Cisplatin and Gemcitabine, which are infused strategically to maximize their impact. This coordinated approach could potentially improve outcomes by attacking the cancer cells from multiple angles simultaneously.

What evidence suggests that this chemotherapy combination is effective for bladder cancer?

This trial will evaluate a combination of four drugs—5-fluorouracil (5-FU), leucovorin, gemcitabine, and cisplatin—for treating bladder cancer. Studies have shown that these drugs stop cancer cells from growing and dividing. Research indicates that gemcitabine and cisplatin together can cause side effects, but these are generally manageable. Adding 5-FU and leucovorin may enhance the cancer-fighting ability of the other drugs, potentially increasing the treatment's effectiveness. This combination has been successfully used in treating other types of cancer, offering hope for patients with bladder cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Arlene Siefker-Radtke, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12049620/

Real-world outcomes of fluorouracil-based second-line ... Our study aimed to evaluate the real-world efficacy and safety of 5-FU-based chemotherapy for BTC patients who had progressed after gemcitabine-based treatment.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39147209/

Long-Term Results of Bladder Preservation With Twice-Daily ... 5-fluorouracil/cisplatin with twice-daily radiation (FCT) or gemcitabine plus daily radiation (GD) are effective chemoradiation (CRT) regimens.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00082706

Study Details | NCT00082706 | Fluorouracil, Leucovorin, ... PURPOSE: This phase II trial is studying how well giving fluorouracil together with leucovorin, gemcitabine, and cisplatin works in treating ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655509000399

A Phase II Trial of Continuous 5-Fluorouracil in Recurrent ... The M-VAC regimen is associated with severe treatment-related toxicities, most notably neutropenic fever, sepsis and mucositis, with a toxic death rate of 3–4%.

5. withpower.com withpower.com/trial/phase-3-urethral-neoplasms-3-2003-0dfe9

Chemotherapy Combination for Bladder Cancer The combination of gemcitabine and cisplatin has shown moderate toxicity in bladder cancer patients, and a regimen including cisplatin, 5-fluorouracil, and ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S153300281170305X

Phase II Trial of 5-Fluorouracil/Leucovorin/Gemcitabine ... Despite acceptable toxicity and a reasonable overall survival, the combination of 5-FU/leucovorin/gemcitabine/cisplatin does not seem to improve current ...

7. researchgate.net researchgate.net/publication/336755435_Nal-IRI_with_5-fluorouracil_5-FU_and_leucovorin_or_gemcitabine_plus_cisplatin_in_advanced_biliary_tract_cancer_-_the_NIFE_trial_AIO-YMO_HEP-0315_an_open_label_non-comparative_randomized_multicenter_ph

(PDF) Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or ... Efficacy and safety of FOLFIRINOX in advanced biliary tract cancer after failure of gemcitabine plus cisplatin: A phase II trial. Article.