Gemcitabine + BCG for Bladder Cancer

(GAIN-BCG Trial)

Recruiting at 43 trial locations

Overseen By Aishwarya Vijendran

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: BCG

Disqualifiers: Neuroendocrine carcinoma, Muscle-invasive cancer, 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: 3

Duration: 12 months

330 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding gemcitabine, a chemotherapy drug, to BCG treatment can more effectively combat bladder cancer that has returned after treatment. BCG, when placed in the bladder, helps the immune system attack cancer cells. Participants will receive either BCG alone or BCG with gemcitabine to determine which approach is more effective. The trial seeks individuals whose bladder cancer has recurred after BCG treatment but has not spread to muscles or other parts of the body. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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

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 to get specific guidance based on your situation.

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

Research has shown that using gemcitabine with BCG holds promise for patients with recurring bladder cancer. Studies indicate that this combination not only fights cancer effectively but is also safe. Patients who received this treatment experienced good results and tolerated it well.

This treatment combines gemcitabine, a drug that stops cancer cells from growing, with BCG, which helps the immune system attack cancer cells. In earlier studies, patients did not report severe side effects, suggesting that this treatment is safe. This is important because it indicates the treatment might work well without causing many unwanted problems.

Since gemcitabine is already approved for other types of cancer, there is confidence in its safety for bladder cancer as well. Overall, the evidence supports the safety of using gemcitabine with BCG for treating recurring bladder cancer. ^{1 2 3 4 5}

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

Researchers are excited about combining gemcitabine with BCG for treating bladder cancer because it offers a potentially more effective approach than traditional BCG therapy alone. Gemcitabine, when used intravesically, works differently by directly targeting cancer cells in the bladder, potentially enhancing the effectiveness of BCG, which stimulates the immune system to fight the cancer. This combination could lead to better outcomes by both directly attacking cancer cells and boosting the body's immune response, providing a dual mechanism that might reduce recurrence rates more effectively than current standard treatments like BCG alone.

What evidence suggests that this trial's treatments could be effective for recurrent non-muscle invasive bladder cancer?

This trial compares two treatment approaches for bladder cancer. In one arm, participants receive BCG alone, which typically outperforms gemcitabine for those without prior BCG treatment. In the other arm, participants receive a combination of gemcitabine and BCG. Research has shown that this combination may effectively treat non-muscle-invasive recurrent bladder cancer. For patients with previous BCG treatment, this combination has demonstrated promising early results in effectiveness and safety. Gemcitabine stops cancer cells from making DNA, potentially killing them, while BCG helps the immune system attack cancer cells. Overall, this combination might eliminate more cancer cells than BCG alone in patients with recurring cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Eugene Pietzak, MD

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for individuals with non-muscle invasive bladder cancer that has returned after BCG therapy. Participants should have a history of the disease responding to treatment before it came back.

Inclusion Criteria

* Documentation of Disease: Histologic confirmation of urothelial carcinoma that is high grade Ta, high grade T1, or Tis (Tis/carcinoma in situ \[CIS\] only disease) within 120 days prior to randomization

* Any component of neuroendocrine carcinoma (i.e., small cell or large cell) is not allowed. Other histologic subtypes/variant histologies are allowed so long as there is a predominantly urothelial component.

\* Note: Pure squamous cell carcinoma or pure adenocarcinoma without a urothelial component are not allowed

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive BCG or Gemcitabine with BCG intravesically over several weeks, with multiple cycles at months 3, 6, and 12

12 months

Weekly visits during treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• BCG Solution
• Gemcitabine

Trial Overview The study is testing if adding Gemcitabine, a chemotherapy drug, to the usual BCG treatment improves outcomes in patients whose bladder cancer has recurred. It's a phase III trial comparing two approaches.

How Is the Trial Designed?

Group I: Arm B (BCG and gemcitabine) Experimental Treatment 8 Interventions

Patients receive gemcitabe intravesically over 1 hour twice weekly on weeks 1 and 10 and once weekly on weeks 4 and 7. Patients also receive BCG intravesically over 2 hours QW on weeks 2, 3, 6, 8 and 9. 2-6 weeks after completing endoscopic assessment, patients receive gemcitable intravesically over 1 hour on week 1 and BCG intravesically over 2 hours on week 2-4 at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, CT scan/MRI and blood and urine sample collection throughout the study.

Group II: Arm A (BCG) Active Control 7 Interventions

Patients receive BCG intravesically over 2 hours QW for 6 weeks. 2-6 weeks after completing endoscopic assessment, patients receive BCG over 2 hours QW for 3 weeks at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, CT scan/MRI and blood and urine sample collection throughout the study.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. 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: Initial Results of a Multicenter Phase II trial ... What about BCG compared to gemcitabine? In the BCG-naïve setting, BCG has been shown to be more effective than gemcitabine. In the BCG refractory setting, the ...

2. targetedonc.com targetedonc.com/view/gemcitabine-bcg-shows-early-promise-in-bcg-exposed-nmibc

Gemcitabine-BCG Shows Early Promise in BCG-Exposed ... BCG with gemcitabine was linked to strong early oncological efficacy and safety in previously treated patients with non–muscle-invasive bladder cancer.

3. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-471942

New Treatment Options for Non–Muscle-Invasive Bladder ... In a multi-institutional retrospective analysis, sequential gemcitabine and docetaxel demonstrated favorable efficacy and safety as a salvage ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38653234/

A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel ... In this single-arm phase 2 trial, GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC.

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

Gemcitabine vs Bacillus Calmette-Guérin for Intravesical ... Gemcitabine is associated with a higher risk of recurrence than BCG in treatment-naïve patients with IR-NMIBC. However, both treatments show comparable ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39797535/

Gemcitabine and docetaxel for high-risk non-muscle- ... The intravesical Gem/Doce regimen demonstrated promising short-term oncological outcomes and was well tolerated in this cohort of patients ...

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

TAR-200 for Bacillus Calmette-Guérin–Unresponsive High- ... Many patients with high-risk non–muscle-invasive bladder cancer (NMIBC) experience disease recurrence (12%-60%) or progression (2%-15%) within 1 ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1558767325001454

A Systematic Review and Meta-Analysis of the ... Our analysis showed CR rates of 36%, 25%, and 18% at 3, 6, and 12 months, respectively. Although BCG remains an established treatment for NMIBC, ...