TAR-200 vs Chemotherapy for Bladder Cancer

(SunRISe-5 Trial)

Not currently recruiting at 157 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TAR-200 (a gemcitabine-releasing system) against traditional chemotherapy for a specific type of bladder cancer. The goal is to determine which treatment helps patients live longer without cancer recurrence. Participants should have high-risk bladder cancer that hasn't spread to muscles and have opted against major bladder surgery. Those whose bladder cancer returned within a year after BCG therapy and are not ready for surgery might find this trial suitable. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

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

Research has shown that TAR-200 is safe and generally well-tolerated. In earlier studies, patients with bladder cancer who used TAR-200 experienced few serious side effects, with most being mild. Some patients reported irritation or discomfort, but these were manageable. The treatment releases medication slowly, which helps reduce side effects. Overall, evidence supports that TAR-200 is safe for people with bladder cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

TAR-200 is unique because it offers a new way to treat bladder cancer by delivering medication directly to the bladder over a sustained period. Unlike traditional chemotherapy, which is administered systemically, TAR-200 uses a novel delivery system called intravesical therapy that releases the drug gradually right at the site of the tumor. This targeted approach not only increases the concentration of the drug where it's needed most but also minimizes side effects common with conventional treatments like Mitomycin C or Gemcitabine. Researchers are excited about TAR-200 because it represents a potential shift towards more effective and safer bladder cancer treatments.

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

Research has shown that TAR-200, a device that slowly releases the drug gemcitabine directly into the bladder, yields promising results for treating bladder cancer. In one study, 82% of patients experienced a complete response, meaning their cancer was no longer detectable. More than half of these patients continued to show no signs of cancer returning after treatment. Another study found that tumors disappeared in 80% of patients using TAR-200. In this trial, participants in Group A will receive TAR-200, while Group B will receive either Mitomycin C or Gemcitabine as a comparator. These findings suggest that TAR-200 could effectively treat high-risk bladder cancer, especially for those who cannot undergo surgery. ^{3 6 7 8 9}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1.

ascopubs.org

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

TAR-200 for Bacillus Calmette-Guérin–Unresponsive High- ...

In phase I studies, TAR-200 was well tolerated and showed preliminary efficacy in patients with muscle-invasive bladder cancer and intermediate ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S1078143924010445

Development of TAR-200: A novel targeted releasing ...

Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus Calmette-Guérin– ...

3.

thelancet.com

thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00358-4/fulltext?rss=yes

interim analysis of a randomised, open-label phase 2 trial

TAR-200 is a novel targeted releasing system designed to provide sustained intravesical delivery of gemcitabine within the bladder. 18 ...

4.

jnj.com

jnj.com/innovativemedicine/us/news-center/oncology/johnson-johnsons-tar-200-monotherapy-demonstrates-highest-complete-response-rate-with-sustained-clinical-benefits-in-patients-with-certain-types-of-bladder-cancer

Johnson & Johnson's TAR-200 monotherapy demonstrates ...

More than 82 percent of patients achieved a complete response, and of those that initially responded to treatment, more than half showed no ...

5.

oncology-central.com

oncology-central.com/slow-release-gemcitabine-device-targets-bladder-cancer-more-effectively/

Slow–release gemcitabine device targets bladder cancer ...

A slow–release device termed TAR-200, which releases a common chemotherapy agent over 3 weeks eliminated tumors in 80% of patients studied.

6.

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].

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39818460/

Development of TAR-200: A novel targeted releasing ...

Preliminary data from the phase IIb SunRISe-1 study demonstrate that TAR-200 monotherapy is safe and effective in patients with bacillus ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02720367

NCT02720367 | Safety and Tolerability of TAR-200 mg in ...

The purpose of this study is to determine if TAR-200, an investigational drug-delivery system is safe and tolerable in patients with recurrent low or ...

9.

jnj.com

jnj.com/media-center/press-releases/new-drug-application-initiated-with-u-s-fda-for-tar-200-the-first-and-only-intravesical-drug-releasing-system-for-patients-with-bcg-unresponsive-high-risk-non-muscle-invasive-bladder-cancer

New Drug Application initiated with U.S. FDA for TAR-200 ...

At data cutoff in May 2024, safety and tolerability data presented at ESMO demonstrated a low occurrence of Grade 3 or higher treatment-related ...