Gemcitabine + Docetaxel vs BCG for Bladder Cancer

(BRIDGE Trial)

Recruiting at 250 trial locations

Overseen By Max Kates, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eastern Cooperative Oncology Group

Disqualifiers: Muscle-invasive cancer, Pregnancy, Severe hypersensitivity, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-12 weeks

870 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatment options for people with non-muscle invasive bladder cancer. The study compares the usual BCG therapy (Bacillus Calmette-Guérin, a type of immunotherapy) with a combination of two drugs, Gemcitabine and Docetaxel, to determine which is more effective at preventing cancer recurrence. Researchers aim to find out if the new drug combination can help patients avoid surgery and improve quality of life. Candidates may qualify if diagnosed with high-grade non-muscle invasive bladder cancer and have not undergone certain previous bladder treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that using Gemcitabine and Docetaxel directly in the bladder is safe for patients who haven't undergone BCG treatment. Most patients have tolerated this treatment well, with many not experiencing severe side effects. In a large study, the treatment proved both effective and tolerable. Another study demonstrated that the combination led to successful outcomes at various stages, although some patients required additional surgery, which is a normal part of follow-up care.

Overall, existing research suggests that using Gemcitabine and Docetaxel in the bladder is safe, with manageable side effects. Prospective trial participants should discuss any specific safety concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for bladder cancer because they bring new approaches compared to the traditional Bacillus Calmette-Guerin (BCG) therapy, which has been the standard. Gemcitabine and Docetaxel, used together, offer a promising alternative by combining two powerful chemotherapy agents to potentially enhance effectiveness against cancer cells. Unlike BCG, which is an immunotherapy that uses a weakened bacterium to stimulate the immune system, Gemcitabine and Docetaxel directly target and disrupt cancer cell growth and division, which might lead to different and potentially improved outcomes. This combination could provide a new option for patients, especially those who may not respond well to BCG.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research shows that combining Gemcitabine and Docetaxel may help treat bladder cancer. In this trial, some participants will receive this combination, which studies have shown can help control cancer for a long time in patients who hadn't received BCG treatment before. One study found that patients tolerated the treatment well and experienced moderate side effects. Another study found it effective as a first treatment for high-risk cases of non-muscle invasive bladder cancer. Overall, these findings suggest that Gemcitabine plus Docetaxel could be a strong alternative to the usual BCG treatment, which another arm of this trial is testing. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-grade non-muscle invasive bladder cancer who haven't had previous intravesical therapy, except perioperative chemo at TURBT time. They must have good performance status (able to carry out daily activities), no severe heart disease, and adequate organ function. Pregnant or breastfeeding individuals are excluded, as well as those with a history of muscle-invasive or advanced urothelial carcinoma.

Inclusion Criteria

My heart function is classified as class 2B or better, despite my history of heart issues or treatments.

I am older than 18 years.

I can understand and am willing to sign the consent form, or I have someone who can do it for me.

Exclusion Criteria

You cannot have had a serious allergic reaction to docetaxel or drugs containing polysorbate 80 in the past.

I had non-invasive bladder cancer, treated and confirmed clear on follow-up tests.

I am not planning to have children and will use or am using effective birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical BCG or Gemcitabine + Docetaxel (GEMDOCE) for non-muscle invasive bladder cancer

6-12 weeks

Follow-up

Participants are monitored for event-free survival, quality of life, cystectomy-free survival, and progression-free survival

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bacillus Calmette Guerin
• Docetaxel
• Gemcitabine

Trial Overview The study compares the effectiveness of Gemcitabine + Docetaxel (GEMDOCE) versus Bacillus Calmette-Guerin (BCG) in treating patients new to BCG treatment for bladder cancer. It measures how long patients remain free from cancer events after these treatments and assesses quality of life, cystectomy-free survival, progression-free survival, safety, and toxicity.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 1 Intervention

BCG

Group II: Arm A Experimental Treatment 2 Interventions

Gemcitabine + Docetaxel

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

Approved in United States as BCG for:

• Non-muscle invasive bladder cancer (NMIBC)
• High-grade NMIBC

Approved in European Union as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer (NMIBC)
• High-grade NMIBC
• Carcinoma in situ of the bladder

Approved in Canada as BCG for:

• Non-muscle invasive bladder cancer (NMIBC)
• High-grade NMIBC

Approved in Japan as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer (NMIBC)
• High-grade NMIBC

Who Is Running the Clinical Trial?

Eastern Cooperative Oncology Group

Lead Sponsor

Trials

272

Recruited

153,000+

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Intravesical gemcitabine and docetaxel therapy shows promising efficacy for high-risk nonmuscle invasive bladder cancer, with 1-year and 2-year recurrence-free survival rates of 86% and 84% in BCG-naive patients, and 80%, 66%, and 51% in BCG-unresponsive patients at 6 months, 1 year, and 2 years, respectively.

The treatment is generally well tolerated, with only 2.3% of patients unable to complete induction therapy and 6.9% experiencing delays or dose reductions due to adverse events, suggesting it could be a viable alternative to BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential intravesical gemcitabine and docetaxel therapy in patients with nonmuscle invasive bladder cancer: a systematic review and meta-analysis. Kawada, T., Yanagisawa, T., Araki, M., et al.[2023]

In a study of 60 patients with non-muscle invasive bladder cancer (NMIBC), the combination of intravesical gemcitabine and docetaxel (Gem/Doce) demonstrated better quality of life outcomes compared to the traditional BCG treatment after 6 months of maintenance therapy.

The Gem/Doce treatment also resulted in fewer side effects than BCG, suggesting it could be a safer and effective alternative for NMIBC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life, Efficacy, and Safety of Sequential Intravesical Gemcitabine + Docetaxel versus BCG for Non-Muscle Invasive Urinary Bladder Cancer: A Pilot Study. Pareek, T., Parmar, K., Sharma, AP., et al.[2022]

In a study of 107 patients with high-risk nonmuscle-invasive bladder cancer (NMIBC) treated with gemcitabine and docetaxel (Gem/Doce), the recurrence-free survival rates were high at 89%, 85%, and 82% at 6, 12, and 24 months, respectively, indicating the efficacy of this treatment in a BCG-naïve population.

The treatment was well-tolerated, with only one patient experiencing a grade 3 adverse event and no cases of disease progression or death from bladder cancer, suggesting that Gem/Doce is a safe alternative during the BCG shortage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer. McElree, IM., Steinberg, RL., Martin, AC., et al.[2022]

In a study of 182 patients with intermediate-risk non-muscle-invasive bladder cancer, the combination of intravesical gemcitabine and docetaxel (Gem/Doce) showed similar recurrence rates and progression outcomes compared to the standard BCG treatment, indicating its potential as an effective alternative.

Both treatment options resulted in low rates of progression to muscle-invasive disease (2.2%) and cancer-specific mortality (1.7%), suggesting that Gem/Doce is a safe and effective choice for managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential Intravesical Gemcitabine and Docetaxel is an Alternative to Bacillus Calmette-Guérin for the Treatment of Intermediate-risk Non-muscle-invasive Bladder Cancer. Tan, WS., McElree, IM., Davaro, F., et al.[2023]

Sequential intravesical gemcitabine/docetaxel (gem/doce) treatment for patients with BCG-unresponsive high-risk nonmuscle invasive bladder cancer showed promising efficacy, with 6-, 12-, and 24-month high-grade recurrence-free survival rates of 78%, 65%, and 49%, respectively, over a median follow-up of 18 months.

The treatment was generally well-tolerated, with mild to moderate adverse effects reported in 57% of patients, and only a small percentage (6.9%) experiencing treatment delays, indicating that gem/doce could be a safe alternative to radical cystectomy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential intravesical gemcitabine/docetaxel provides a durable remission in recurrent high-risk NMIBC following BCG therapy. Yim, K., Melnick, K., Mott, SL., et al.[2023]

In a study of 35 patients with non-muscle-invasive bladder cancer who experienced BCG treatment failure, sequential intravesical gemcitabine and docetaxel (gem/doce) showed a promising 60% progression-free survival rate at two years, indicating its efficacy as a salvage therapy.

The treatment was generally safe and well-tolerated, with only 37% of patients experiencing adverse events, and a high overall survival rate of 94% at two years, suggesting that gem/doce could be a viable option for patients who are not candidates for radical cystectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage therapy for BCG failure with intravesical sequential gemcitabine and docetaxel in patients with recurrent NMIBC. Garneau, CA., Marcotte, N., Lacombe, L., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6218180/

Sequential Intravesical Gemcitabine and Docetaxel for the ... Median follow up for treatment success was 6 months in all patients and 13 months for responders. Five patients were unable to tolerate a full induction course.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04386746

Intravesical Gemcitabine and Docetaxel for BCG naïve Non ... A single-arm, two-stage, open-label, phase 2 study investigating the safety and efficacy of intravesical gemcitabine/docetaxel for bacillus Calmette-Guerin (BCG)- ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419628085

Weekly chemotherapy with docetaxel, gemcitabine and ... Weekly docetaxel, gemcitabine plus cisplatin is a highly effective treatment for chemotherapy-naïve advanced TCC, and causes only moderate toxicity. This ...

4. auajournals.org auajournals.org/doi/10.1097/JU.0000000000002740

Sequential Intravesical Gemcitabine and Docetaxel for ... We report outcomes of a large cohort of patients with high-risk BCG-naïve NMIBC treated with Gem/Doce as a first-line therapy.

5. cancernetwork.com cancernetwork.com/view/docetaxel-management-advanced-or-metastatic-urothelial-tract-cancer

Docetaxel in the Management of Advanced or Metastatic ... Phase II studies of single-agent docetaxel (Taxotere) yielded promising results in advanced or metastatic transitional cell carcinoma (TCC) of the urothelium.

6. eviq.org.au eviq.org.au/medical-oncology/urogenital/bladder-and-urothelial/4320-bladder-intravesical-docetaxel-and-gemcitabin

4320-Bladder intravesical DOCEtaxel and gemcitabine Milbar et al. validated these results in a similar population reporting disease-free survival (DFS) of 42% at 1 year and 24% at 2 years (median DFS 7 months).

7. urology.wisc.edu urology.wisc.edu/wp-content/uploads/2022/09/Sequential-Intravesical-Gemcitabine-and-Docetaxel-for-bacillus-Calmette-Gue-rin-Nai-ve-High-Risk-Nonmuscle-Invasive-Bladder-Cancer.pdf

Sequential-Intravesical-Gemcitabine-and-Docetaxel-for- ... Sequential intravesical gemcitabine and docetaxel (Gem/Doce) was first reported in 2014 as an efficacious and well tolerated therapy for pa- tients in whom BCG ...