BCG + Gemcitabine for Relapsed Bladder Cancer

Not currently recruiting at 7 trial locations

Overseen By Guido Dalbagni, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Pregnancy, Active tuberculosis, Immunosuppression, others

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

Compensation: Varies

Number of Visits: 8

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments: Bacillus Calmette-Guérin (BCG, a type of immunotherapy) and gemcitabine (a chemotherapy drug), for bladder cancer that has returned after initial BCG treatment. Researchers aim to determine the safest dose of gemcitabine when combined with BCG and assess the effectiveness of this combination in treating the cancer. Individuals with non-muscle invasive bladder cancer that has recurred within 24 months after their last BCG treatment may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this combination therapy.

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 using Bacillus Calmette-Guérin (BCG) with gemcitabine can be a treatment option that patients tolerate well. One study found that about 62% of patients who received only BCG experienced side effects, while only 38% of those who received only gemcitabine reported similar issues. This suggests that gemcitabine might cause fewer side effects than BCG.

When used together, these two drugs have shown promising safety results in studies. Patients with bladder cancer who received both treatments did not report any unexpected side effects. Researchers are testing this combination to determine the right dose of gemcitabine that keeps side effects mild or manageable. Overall, research indicates that this treatment is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Bacillus Calmette-Guérin (BCG) and Gemcitabine for relapsed bladder cancer because it merges immunotherapy with chemotherapy in a novel way. Unlike traditional treatments that often rely on just one method, this combo uses BCG to help the immune system fight cancer cells while Gemcitabine directly attacks them, potentially enhancing overall effectiveness. This treatment is given intravesically, meaning it’s delivered directly into the bladder, which can concentrate the effects right where they're needed and may reduce systemic side effects. This dual approach could offer new hope for patients who have not responded to standard therapies.

What evidence suggests that this combination of BCG and gemcitabine might be an effective treatment for relapsed bladder cancer?

In this trial, participants will receive a combination of BCG and gemcitabine to treat relapsed bladder cancer. Research has shown that both BCG and gemcitabine treat bladder cancer effectively, each with distinct strengths. Studies have found that BCG can keep the cancer away longer compared to gemcitabine alone. However, while gemcitabine is also effective, the cancer may return sooner than with BCG. By combining these two treatments, the researchers aim to leverage the benefits of both to improve patient outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Eugene Pietzak, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with high-grade non-muscle invasive bladder cancer that has returned after BCG treatment. Participants must have had all visible tumors removed recently, no upper urinary tract cancer in the last year, and a good performance status. Pregnant individuals, those with BCG contraindications or severe reactions to it, active tuberculosis, immune deficiencies, muscle-invasive or metastatic urothelial carcinoma are excluded.

Inclusion Criteria

I can care for myself but may need occasional help.

Informed consent

My bladder cancer has returned within 2 years after BCG treatment.

Exclusion Criteria

My cancer has spread to areas like the urethra, ureter, or renal pelvis.

I have or am being treated for advanced bladder cancer.

My bladder cancer did not respond to BCG treatment after receiving most of the doses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination intravesical chemoimmunotherapy with BCG and gemcitabine. Gemcitabine is administered twice-weekly at weeks 1, 4, 7, and 10, and BCG is administered once-weekly at weeks 2, 3, 5, 6, 8, and 9.

10 weeks

8 visits for gemcitabine, 6 visits for BCG (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including urine cytology and cystoscopy.

6 months

Regular follow-up visits (in-person)

Long-term follow-up

Participants are monitored for long-term safety and effectiveness, with a focus on disease-free status.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Bacillus Calmette-Guérin (BCG)
• Gemcitabine

Trial Overview The study tests the safety and effectiveness of combining Bacillus Calmette-Guérin (BCG) with increasing doses of Gemcitabine in treating bladder cancer that's come back after BCG therapy. The goal is to find the highest dose of Gemcitabine that works well with BCG and causes few or mild side effects.

How Is the Trial Designed?

Group I: Bacillus Calmette-Guérin (BCG) and Gemcitabine Experimental Treatment 2 Interventions

Eligible patients will receive combination intravesical chemoimmunotherapy. Treatment is sequential, with twice-weekly intravesical gemcitabine given at weeks 1, 4, 7, and 10, for a total of 8 doses, administered in a standard fashion. In phase I, the dose of gemcitabine will depend on the dose level being assessed for the determination of the MTD. phase II, 1 dose level will be given (the MTD from phase I). Fixed doses of once-weekly intravesical BCG therapy (TICE strain, 50 mg) will be given at weeks 2 (+/- 2 days), 3 (+/- 2 days), 5 (+/- 2 days), 6 (+/- 2 days), 8 (+/- 2 days), and 9 (+/- 2 days), for a total of 6 doses, also administered in a standard fashion. All intravesical therapy will be administered in the chemotherapy suite on an outpatient basis, in accordance with standard clinical practice. Intravesical therapies will be retained in the bladder for up to 2 h (BCG) or 1 h (gemcitabine), or as tolerated.

Bacillus Calmette-Guérin (BCG) is already approved in United States, Canada, European Union for the following indications:

Approved in United States as TheraCys for:

• Non-muscle invasive bladder cancer
• Upper tract urothelial carcinoma

Approved in Canada as Immun BCG for:

• Non-muscle invasive bladder cancer

Approved in European Union as TICE BCG for:

• Non-muscle invasive bladder cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Intravesical gemcitabine (Gem) shows a lower incidence of side effects like dysuria and hematuria compared to Bacille Calmette-Guérin (BCG) in treating non-muscle invasive bladder cancer, based on a meta-analysis of 386 subjects from 5 trials.

Both treatments have similar efficacy in terms of recurrence and progression rates, indicating that Gem could be a safer alternative to BCG, but further high-quality trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of intravesical gemcitabine vs Bacille Calmette-Guérin for adjuvant treatment of non-muscle invasive bladder cancer: a meta-analysis. Ye, Z., Chen, J., Hong, Y., 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 35 patients with BCG-refractory superficial bladder cancer, intravesical Gemcitabine demonstrated a 60% success rate in preventing tumor recurrences over an 18-month follow-up period.

The treatment was well tolerated with low and mild adverse events, making Gemcitabine a promising alternative for patients who do not respond to BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of BCG non-responders with fixed dose intravesical gemcitabine in superficial transitional cell carcinoma of urinary bladder. Mohanty, NK., Nayak, RL., Vasudeva, P., et al.[2021]

In a study of 80 patients with high-risk non-muscle-invasive bladder cancer who failed BCG therapy, intravesical gemcitabine significantly reduced the disease recurrence rate (52.5%) compared to BCG (87.5%), indicating its potential as an effective second-line treatment option.

Kaplan-Meier analysis showed that gemcitabine provided a higher 2-year recurrence-free survival rate (19%) compared to BCG (3%), suggesting that gemcitabine may offer better long-term outcomes for patients after BCG failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial. Di Lorenzo, G., Perdonà, S., Damiano, R., et al.[2022]

In a study of 592 patients receiving intravesical therapy for non-muscle invasive bladder cancer, 78% reported side effects, with bladder symptoms and fatigue being the most common.

Reduced-dose BCG was associated with the lowest prevalence and severity of fatigue, while gemcitabine led to the highest prevalence of body aches, indicating significant differences in tolerability among the treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Side Effects and Tolerability Between Intravesical Bacillus Calmette-Guerin, Reduced-Dose BCG and Gemcitabine for Non-Muscle Invasive Bladder Cancer. Kuperus, JM., Busman, RD., Kuipers, SK., et al.[2022]

In a pilot study involving 9 patients with BCG-resistant T1G3 bladder cancer, gemcitabine (GEM) was well tolerated with no severe adverse events, and 3 patients remained recurrence-free for up to 21 months.

Compared to 10 patients treated with BCG, GEM showed promising short-term efficacy, with a higher overall survival rate (100% for GEM vs. 80% for BCG), suggesting GEM may be a viable alternative for patients unsuitable for radical treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical gemcitabine in BCG-refractory T1G3 transitional cell carcinoma of the bladder: a pilot study. Gacci, M., Bartoletti, R., Cai, T., et al.[2022]

In a study of 64 patients with high-risk superficial bladder cancer, bacillus Calmette-Guérin (BCG) treatment resulted in a significantly lower recurrence rate (28.1%) compared to gemcitabine (53.1%), indicating that BCG is more effective for this condition.

Gemcitabine was better tolerated than BCG, with fewer patients needing delayed treatment or withdrawal, suggesting it could be a suitable alternative for those who cannot tolerate BCG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guérin versus gemcitabine for intravesical therapy in high-risk superficial bladder cancer: a randomised prospective study. Porena, M., Del Zingaro, M., Lazzeri, M., et al.[2022]

Intravesical gemcitabine is a safe and effective treatment option for bladder cancer patients who have not responded to bacillus Calmette-Guérin (BCG) therapy, with no serious adverse events reported and only a few patients discontinuing treatment due to side effects.

Among 69 patients treated, 27 achieved a complete response, and those with a complete response experienced a delayed need for cystectomy, indicating that gemcitabine can help manage the disease and potentially avoid more invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical gemcitabine for high risk, nonmuscle invasive bladder cancer after bacillus Calmette-Guérin treatment failure. Sternberg, IA., Dalbagni, G., Chen, LY., et al.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2405456924001731

Comparative Effectiveness of Bacillus Calmette-Guérin and ... Bacillus Calmette-Guérin (BCG) led to better outcomes than gemcitabine + docetaxel (Gem/Doce). Monthly maintenance therapy improved recurrence-free survival.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39306526/

Comparative Effectiveness of Bacillus Calmette-Guérin and ... Bacillus Calmette-Guérin (BCG) led to better outcomes than gemcitabine + docetaxel (Gem/Doce). Monthly maintenance therapy improved recurrence-free survival.

3. auajournals.org auajournals.org/doi/10.1097/JU.0000000000004472

Gemcitabine vs Bacillus Calmette-Guérin for Intravesical ... Recurrence-free survival was significantly longer in the BCG group compared with the gemcitabine group (median recurrence-free survival: 31 vs ...

4. urotoday.com urotoday.com/conference-highlights/suo-2024/suo-2024-bladder-cancer/156722-suo-2024-the-efficacy-of-salvage-bcg-for-recurrent-non-muscle-invasive-bladder-cancer-after-first-line-gemcitabine-and-docetaxel.html

SUO 2024: The Efficacy of Salvage BCG for Recurrent Non ... Dr. McElree concluded that in a cohort of patients with recurrent NMIBC, intravesical BCG was a reasonable treatment option following gemcitabine plus ...

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

Efficacy of intravesical gemcitabine instillation compared ... The mean RFS was 15.92 months in the gemcitabine group and 19.84 months in the BCG group, with no statistically significant difference (p=0.397) ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1078143923001187

The efficacy and safety outcomes of lower dose BCG ... This study aimed to assess both efficacy and safety outcomes of lowering the dose of BCG compared to intravesical chemotherapies in non–muscle-invasive bladder ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5676758/

Oncological Outcomes of Sequential Intravesical ... Phase 2 trials in patients with BCG refractory/unresponsive disease have reported recurrence free-survival of up to 28% at 1 year [11].

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04179162

NCT04179162 | Bacillus Calmette-Guérin (BCG) and ... This study will test the safety of BCG and gemcitabine in people who have BCG-relapsing Non-Muscle Invasive Bladder Cancer (NMIBC).

9. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-01651

TAR-200 for Bacillus Calmette-Guérin–Unresponsive High- ... Patients with BCG-unresponsive CIS have a high risk of progression and limited treatment options, thus guidelines recommend cystectomy.