TAR-200 vs Chemotherapy for Bladder Cancer

(SunRISe-5 Trial)

Recruiting at 122 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: CIS, Muscle-invasive cancer, Polyuria, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

250 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare disease free survival (DFS) in participants with recurrence of papillary-only high-risk non-muscle-invasive bladder cancer (HR-NMIBC) within 1 year of last dose of Bacillus Calmette-Guérin (BCG) therapy and who refused or are unfit for Radical Cystectomy (RC), receiving TAR-200 versus investigator's choice of single agent intravesical chemotherapy.

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 team or your doctor.

What data supports the effectiveness of the TAR-200 treatment for bladder cancer?

Research shows that TAR-200, which releases gemcitabine directly into the bladder, has been effective in patients with muscle-invasive bladder cancer who are not suitable for more aggressive treatments. Additionally, intravesical gemcitabine has shown promising results in treating bladder cancer with low toxicity, suggesting that TAR-200 could be a beneficial option. ^{1 2 3 4 5}

Is TAR-200 safe for use in humans?

TAR-200, which releases gemcitabine directly into the bladder, has been studied for safety in patients with muscle-invasive bladder cancer. The studies show that it is generally safe and well-tolerated, with low urinary and systemic toxicity. ^{1 2 4 6 7}

How is the TAR-200 treatment different from other bladder cancer treatments?

TAR-200 is unique because it is an intravesical (inside the bladder) drug delivery system that continuously releases gemcitabine directly into the bladder over a 21-day cycle, minimizing systemic side effects and making it suitable for patients who cannot undergo standard curative treatments. ^{1 2 3 4 8}

Research Team

Janssen Research & Development, LLC Clinical trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for people with high-risk bladder cancer that came back within a year after BCG therapy and who can't have or don't want full bladder removal surgery. They should be able to perform daily activities (ECOG grade 0-2) and not have certain rare cancer types.

Inclusion Criteria

I have chosen not to or cannot undergo major bladder surgery.

My cancer is mainly urothelial but not neuroendocrine or small cell type.

My bladder cancer is confirmed high-risk but not invasive.

Exclusion Criteria

I have had CIS or advanced urothelial carcinoma at some point since my diagnosis.

I have a history of producing more than 4 liters of urine in a day.

I have been treated with TAR-200 before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive either TAR-200 every 3 weeks or intravesical chemotherapy weekly

6-12 weeks

Every 3 weeks for TAR-200, weekly for chemotherapy

Maintenance Treatment

Participants receive TAR-200 every 12 weeks or chemotherapy every 4 weeks

Up to 6 years 7 months

Every 12 weeks for TAR-200, every 4 weeks for chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years 7 months

Treatment Details

Interventions

• Gemcitabine
• Mitomycin C
• TAR-200

Trial Overview The study compares TAR-200, a new treatment, with the doctor's choice of standard chemotherapy drugs like Mitomycin C or Gemcitabine in patients refusing or unfit for radical cystectomy. It focuses on how long patients stay free from cancer after treatment.

Participant Groups

Group I: Group A: TAR-200 Experimental Treatment 1 Intervention

Participants will receive intravesical TAR-200 every 3 weeks during an induction phase and every 12 weeks during a maintenance phase.

Group II: Group B: Mitomycin C (MMC) or Gemcitabine Active Control 2 Interventions

Participants will receive either single agent intravesical MMC or gemcitabine every week during an induction phase and every 4 weeks during a maintenance phase.

TAR-200 is already approved in United States for the following indications:

Approved in United States as TAR-200 for:

• Breakthrough Therapy Designation for BCG-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC)

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

TAR-200, a novel drug delivery system for gemcitabine, was found to be generally safe and well tolerated in a study of 35 elderly patients with muscle-invasive bladder cancer who were unfit for standard treatment.

The treatment showed promising preliminary efficacy, with a 40% overall response rate and a median overall survival of 27.3 months, indicating it could be a valuable option for patients with limited treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Preliminary Efficacy of TAR-200 in Patients With Muscle-invasive Bladder Cancer Who Refused or Were Unfit for Curative-intent Therapy: A Phase 1 Study. Tyson, MD., Morris, D., Palou, J., et al.[2023]

The TAR-200 system for delivering gemcitabine directly into the bladder was found to be safe and well tolerated in a phase I study involving 23 patients with muscle-invasive bladder cancer (MIBC), with no intolerable side effects reported.

Preliminary efficacy results showed that a significant number of patients experienced pathologic downstaging after treatment, with some achieving complete or partial responses, indicating potential effectiveness of this localized treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial. Daneshmand, S., Brummelhuis, ISG., Pohar, KS., 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]

In a phase II study involving 40 patients with BCG-refractory bladder cancer, biweekly intravesical treatment with gemcitabine resulted in a 95% rate of negative post-treatment cystoscopy and cytology after 6 months, indicating strong efficacy against transitional cell carcinomas.

The treatment was associated with very low urinary and systemic toxicity, with no significant changes in biochemical profiles, suggesting it is a safe option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study. Gunelli, R., Bercovich, E., Nanni, O., et al.[2022]

In a phase II trial involving 36 patients with advanced transitional-cell carcinoma, the combination of weekly paclitaxel and gemcitabine showed a significant response rate, with 69.4% of patients achieving major responses, including 41.7% with complete responses.

Despite its efficacy, the treatment was associated with a concerning incidence of pulmonary toxicity, leading to a recommendation against its use due to safety concerns, particularly after observing severe toxicities in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly paclitaxel and gemcitabine in advanced transitional-cell carcinoma of the urothelium: a phase II Hoosier Oncology Group study. Li, J., Juliar, B., Yiannoutsos, C., 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]

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]

The gemcitabine and carboplatin combination treatment for advanced transitional cell carcinoma (TCC) showed a 56.1% overall response rate, making it an effective alternative to standard cisplatin-based therapies, especially for patients with impaired renal function or poor performance status.

Despite significant hematologic toxicities, such as neutropenia and anemia, the treatment had an acceptable safety profile, allowing for administration in elderly patients and those with other health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy. Nogué-Aliguer, M., Carles, J., Arrivi, A., et al.[2022]

References

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

Safety, Tolerability, and Preliminary Efficacy of TAR-200 in Patients With Muscle-invasive Bladder Cancer Who Refused or Were Unfit for Curative-intent Therapy: A Phase 1 Study. [2023]

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

The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial. [2022]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study. [2022]

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

Weekly paclitaxel and gemcitabine in advanced transitional-cell carcinoma of the urothelium: a phase II Hoosier Oncology Group study. [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

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]

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

Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy. [2022]