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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of Gemcitabine (Gemzar) combined with Docetaxel for treating non-muscle invasive bladder cancer, which has not penetrated the muscle layer. Researchers are exploring it as a first-line treatment, particularly when Bacillus Calmette-Guérin (BCG) therapy is ineffective or unavailable. Suitable candidates for this trial have intermediate or high-risk non-muscle invasive bladder cancer and have not previously received BCG treatment. Participants will undergo treatment once a week for six weeks to assess its impact on preventing cancer recurrence. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that gemcitabine is generally safe for treating bladder cancer. Patients with non-muscle invasive bladder cancer tolerated gemcitabine well in studies. It significantly lowers the risk of cancer returning compared to a simple saltwater solution.

Researchers tested the combination of gemcitabine and docetaxel in patients who did not respond to the usual BCG treatment. This combination showed a 50-60% chance of patients being cancer-free for a year, suggesting it can be effective and safe for those who cannot use BCG.

The FDA has approved gemcitabine for bladder cancer, indicating it has passed safety checks for certain uses. However, like any treatment, risks may exist. Always consult your doctor to understand what this means for you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Unlike the standard treatments for bladder cancer, which often include surgery, chemotherapy with drugs like cisplatin, or immunotherapy, Gemcitabine offers a unique approach. Researchers are excited about this treatment because Gemcitabine, combined with Docetaxel, is administered directly into the bladder, allowing for targeted therapy that might reduce systemic side effects. This method could enhance the drug's effectiveness against the cancer cells in the bladder while minimizing impact on the rest of the body. Additionally, the combination of Gemcitabine and Docetaxel may work synergistically, potentially offering improved outcomes compared to the standard single-agent therapies.

What evidence suggests that Gemcitabine might be an effective treatment for non-muscle invasive bladder cancer?

Research has shown that gemcitabine can effectively treat non-muscle invasive bladder cancer (NMIBC) when other treatments, like BCG, fail. Studies found that for patients unresponsive to BCG, gemcitabine proved more effective. In this trial, participants will receive a combination of gemcitabine and docetaxel, which has successfully treated NMIBC. This combination is already a standard option for patients who cannot use BCG or did not benefit from it. While researchers continue to study gemcitabine as a first-choice treatment, its use after BCG failure is well-supported by current evidence. ^{6 7 8 9 10}

Who Is on the Research Team?

Juan Chipollini, MD

Principal Investigator

University of Arizona

Are You a Good Fit for This Trial?

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 have had surgery to remove a bladder tumor.

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

I can consent in English or Spanish and have signed the consent form.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Gemcitabine induction Experimental Treatment 1 Intervention

Patients will receive Gemcitabine + Docetaxel 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+

Published Research Related to This Trial

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, 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 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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10323448/

Gemcitabine First-Line Therapy for High-Grade Bladder Cancer Together these data suggest that gemcitabine is a reasonable and well-established second-line treatment option for patients who have failed BCG.

2. urotoday.com urotoday.com/conference-highlights/suo-2024/suo-2024-bladder-cancer/156743-suo-2024-initial-results-of-a-multicenter-phase-ii-trial-of-intravesical-gemcitabine-plus-bcg-for-patients-with-bcg-exposed-non-muscle-invasive-bladder-cancer.html

SUO 2024: Gemcitabine+BCG for BCG-exposed NMIBC In the BCG-naïve setting, BCG has been shown to be more effective than gemcitabine. In the BCG refractory setting, the reverse is seen with superior efficacy ...

3. nrgoncology.org nrgoncology.org/Home/News/Post/updated-results-of-nrg-oncology-trial-display-effectiveness-of-gemcitabine-and-daily-radiation-for-bladder-preservation-in-muscle-invasive-bladder-cancer-patients

Updated Results of NRG Oncology Trial Display ... 58% of patients in the FCT treatment arm had treatment related-grade 3 or 4 hematologic, gastrointestinal, or genitourinary toxicities and 52% ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666168324002234

Bladder Cancer The Safety, Tolerability, and Preliminary ... In previous studies, TAR-200 was shown to be safe and well tolerated, and demonstrated preliminary efficacy in participants with MIBC [14], [16].

5. kosinmedj.org kosinmedj.org/journal/view.php?doi=10.7180/kmj.24.143

Efficacy of intravesical gemcitabine vs. BCG for NMIBC Among them, 42 patients received intravesical gemcitabine to reduce bladder recurrence and 36 patients received intravesical BCG. The BCG ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10998271/

A Phase 1b Study - PubMed Central - NIH In this phase 1b study, TAR-200, a novel drug delivery system, was safe and well tolerated in participants with intermediate-risk non–muscle-invasive bladder ...

7. urotoday.com urotoday.com/conference-highlights/aua-2025/aua-2025-bladder-cancer/160107-aua-2025-prospective-open-label-study-to-evaluate-the-safety-and-efficacy-of-intravesical-sustained-release-gemcitabine-docetaxel-combination-ndv-01-in-high-risk-nmibc.html

AUA 2025: Prospective Open Label Study to Evaluate ... Gemcitabine + docetaxel has shown a 50-60% 12 month recurrence free survival in BCG unresponsive high risk non muscle invasive bladder cancer, ...

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2680547

Effect of Intravesical Instillation of Gemcitabine vs Saline ... Intravesical instillation of gemcitabine, compared with saline, significantly reduced the risk of recurrence over a median of 4.0 years.

9. sciencedirect.com sciencedirect.com/science/article/pii/S107814392200059X

Clinical-Bladder cancer The safety, tolerability, and efficacy ... Conclusion. Controlled intravesical gemcitabine release via TAR-200 was safe and well tolerated in patients with MIBC. Graphical abstract.

10. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-gemcitabine-intravesical-system-non-muscle-invasive-bladder-cancer

FDA approves gemcitabine intravesical system The prescribing information includes warnings and precautions describing risks of administering gemcitabine intravesical system in patients ...