Gemcitabine for Bladder Cancer

Overseen By Michele Chu-Pilli

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arizona

Disqualifiers: T2 or higher UC, Active malignancies, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

25 Participants Needed

Trial Summary

What is the purpose of this trial?

Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumor recurrence after bladder tumor resection. For high-risk non-muscle invasive bladder cancer, immunotherapy in the form of intravesical Bacillus Calmette-Guérin (BCG) can be effective as first-line, nevertheless, the response rate to BCG is suboptimal with many patients failing treatment. Following BCG-failure, however, very few effective therapeutic options exist besides life-changing cystectomy. In addition, nationwide shortages of BCG have pushed the use of alternative intravesical therapies for non-muscle invasive bladder cancer. At Banner University Medical-Tucson, the use of intravesical Gemcitabine is considered as standard treatment for patients with bladder cancer who are unable to get BCG or have failed prior BCG treatment. The role of Gemcitabine as treatment for NBMIC is poorly understood. The purpose of this study is to gain a better understanding of the use of Gemcitabine intravesical chemotherapy for non-muscle invasive bladder cancer in a prospective cohort of patients.

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 study team or your doctor.

What data supports the effectiveness of the drug Gemcitabine for treating bladder cancer?

Research shows that Gemcitabine is effective in treating advanced bladder cancer, with response rates of 23% to 29% when used alone and 41% to 57% when combined with cisplatin. It is also associated with better safety and fewer severe side effects compared to the standard MVAC regimen. ^{1 2 3 4 5}

Is gemcitabine safe for treating bladder cancer?

Gemcitabine has been studied for safety in treating bladder cancer, and it is generally considered safe for use in humans. Some studies have specifically looked at its safety when used directly in the bladder, showing it to be a tolerable option for patients, even those who cannot use other treatments. ^{6 7 8 9 10}

How does the drug Gemcitabine differ from other treatments for bladder cancer?

Gemcitabine is unique because it has a favorable safety profile compared to the standard MVAC regimen, with fewer severe side effects like mucositis (painful inflammation of the mouth) and neutropenic fever (fever due to low white blood cells). It can be used alone or in combination with cisplatin, offering a safer alternative for advanced bladder cancer treatment. ^{1 3 11 12 13}

Research Team

Juan Chipollini, MD

Principal Investigator

University of Arizona

Eligibility Criteria

This trial is for adults over 18 with intermediate or high-risk non-muscle invasive bladder cancer who haven't had BCG treatment. They must understand English or Spanish, agree to follow the study rules, and be available for its duration. Excluded are those allergic to Gemcitabine, pregnant or breastfeeding women, patients with advanced bladder cancer stages, other active cancers, certain psychiatric conditions or substance abuse issues.

Inclusion Criteria

I am 18 years old or older.

I have had surgery to remove a bladder tumor.

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

I do not have any active cancer other than the one being treated in this study.

I have cancer in my upper urinary tract.

Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the investigator, the patient would be unable to comply with the protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-3 weeks

1 visit (in-person)

Treatment

Participants receive Gemcitabine once weekly for 6 weeks

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Monthly visits (in-person) for maintenance therapy assessment

Maintenance Therapy (optional)

Participants may opt into monthly maintenance therapy for 10 months

10 months

Treatment Details

Interventions

• Gemcitabine

Trial Overview The trial studies how well Gemcitabine works as a chemotherapy given directly into the bladder (intravesical) for patients who can't receive BCG therapy or didn't respond to it. It aims to provide better insights on treating non-muscle invasive bladder cancer with this drug in a prospective patient group.

Participant Groups

Group I: Gemcitabine induction Experimental Treatment 1 Intervention

Patients will receive Gemcitabine once weekly for 6 weeks.

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Findings from Research

The combination of gemcitabine (GEM) and triptolide (TPL) significantly enhances the anticancer effects against bladder cancer cells compared to using either drug alone, as shown in experiments with EJ and UMUC3 cell lines.

This combination treatment leads to cell cycle arrest at the G1 phase and increased apoptosis, indicating a more effective mechanism of action through the inhibition of specific proteins and pathways, including the AKT/GSK3β signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic antitumour effects of triptolide plus gemcitabine in bladder cancer. Yang, Y., Zhang, LJ., Bai, XG., et al.[2022]

Gemcitabine maintenance therapy after standard platinum-gemcitabine treatment in metastatic bladder cancer patients showed a median progression-free survival (PFS) of 46 weeks, indicating a potential benefit in extending survival for those who responded to initial treatment.

The treatment was associated with a low toxicity profile, with only 30.4% of patients experiencing grade 3 hematotoxicity, suggesting that gemcitabine maintenance is a relatively safe option for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival. Kuş, T., Aktaş, G.[2020]

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 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]

In a study of 41 previously untreated patients with advanced transitional cell carcinoma, gemcitabine demonstrated a 24.3% overall response rate, with three complete responses and six partial responses, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with manageable side effects; however, some patients experienced significant neutropenia and other grade 3 toxicities, suggesting that while gemcitabine is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine: a promising new agent in the treatment of advanced urothelial cancer. Moore, MJ., Tannock, IF., Ernst, DS., et al.[2022]

In a phase I study involving 18 patients with bladder cancer resistant to BCG therapy, gemcitabine administered intravesically showed substantial activity, with 7 patients achieving a complete response.

The treatment was generally safe, with minimal severe toxicity observed; the recommended dose for further studies is 2,000 mg, despite some patients experiencing mild side effects like hematuria and myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder. Dalbagni, G., Russo, P., Sheinfeld, J., et al.[2022]

Gemcitabine can be safely administered intravesically in a mouse model of superficial bladder cancer, with no significant side effects observed across various doses (0.5, 2.5, and 10 mg).

The treatment resulted in a significant reduction in bladder weight, indicating effective antitumor activity compared to control groups, suggesting gemcitabine could be a promising alternative for treating superficial bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antineoplastic effect of gemcitabine in an animal model of superficial bladder cancer. Nativ, O., Dalal, E., Laufer, M., et al.[2022]

The combination of gemcitabine and irinotecan (Irinogem) showed promising efficacy in treating metastatic bladder cancer, with 8 out of 13 evaluable patients achieving an objective response, including 2 complete responses and 6 partial responses, and a median progression-free survival of 8.78 months.

The treatment was associated with manageable toxicity, with no toxic deaths reported, although some patients experienced significant side effects like neutropenia and diarrhea. However, the study's early closure due to funding issues limits the ability to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. Chaudhary, UB., Verma, N., Keane, T., et al.[2022]

In a Phase II study involving 56 elderly and unfit patients with advanced bladder carcinoma, the combination of gemcitabine and carboplatin showed a 36% overall response rate, indicating its efficacy as a first-line treatment.

The treatment was associated with manageable toxicity, with significant side effects including neutropenia (27%) and anemia (18%), but it still represents a viable option for patients who cannot tolerate cisplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and carboplatin combination as first-line treatment in elderly patients and those unfit for cisplatin-based chemotherapy with advanced bladder carcinoma: Phase II study of the Hellenic Co-operative Oncology Group. Linardou, H., Aravantinos, G., Efstathiou, E., et al.[2022]

In a study of 35 patients with BCG failure, intravesical gemcitabine demonstrated a 60% success rate in preventing tumor recurrences over an 18-month follow-up period, indicating its efficacy as an alternative treatment.

The treatment was well tolerated with low and mild adverse events, suggesting that gemcitabine is a safe option for patients who do not respond to BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesicle gemcitabine in management of BCG refractory superficial TCC of urinary bladder-our experience. Mohanty, NK., Nayak, RL., Vasudeva, P., et al.[2022]

Gemcitabine (GEM) is a promising chemotherapy option for metastatic bladder cancer, showing acceptable toxicity and enhanced antitumor activity, but it can lead to unexpected complications.

In a case study of a 56-year-old male patient, GEM combined with cisplatin resulted in severe necrotizing vasculitis and muscle damage, highlighting the importance of monitoring for unusual symptoms during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine-induced vasculitis in advanced transitional cell carcinoma of the bladder. Birlik, M., Akar, S., Tuzel, E., et al.[2022]

Gemcitabine has shown significant effectiveness in treating superficial BCG-resistant bladder cancer and is a viable option for BCG-intolerant patients through intravesical instillation.

In advanced bladder cancer, the combination of gemcitabine and cisplatin is recognized as a standard first-line treatment, making gemcitabine a flexible choice for various patient conditions, including those who are unfit for more aggressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in bladder cancer. El Karak, F., Flechon, A.[2022]

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]

References

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

Synergistic antitumour effects of triptolide plus gemcitabine in bladder cancer. [2022]

2. Turkey pubmed.ncbi.nlm.nih.gov

Maintenance treatment with gemcitabine have a promising activity on metastatic bladder cancer survival. [2020]

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

Gemcitabine in advanced bladder cancer. [2022]

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

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

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

Gemcitabine: a promising new agent in the treatment of advanced urothelial cancer. [2022]

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

Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder. [2022]

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

Antineoplastic effect of gemcitabine in an animal model of superficial bladder cancer. [2022]

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

A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer. [2022]

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

Gemcitabine and carboplatin combination as first-line treatment in elderly patients and those unfit for cisplatin-based chemotherapy with advanced bladder carcinoma: Phase II study of the Hellenic Co-operative Oncology Group. [2022]

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

Intravesicle gemcitabine in management of BCG refractory superficial TCC of urinary bladder-our experience. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Gemcitabine-induced vasculitis in advanced transitional cell carcinoma of the bladder. [2022]

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

Gemcitabine in bladder cancer. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. [2022]