ST-02 for Urothelial Carcinoma

Recruiting at 2 trial locations

Overseen By Dasa Durkotova

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of British Columbia

Must not be taking: BCG, Systemic chemotherapy

Disqualifiers: Pregnancy, High-grade bladder cancer, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 6 weeks

70 Participants Needed

Trial Summary

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

The trial does not specify if you need to stop taking your current medications, but you cannot be actively treated with intravesical or systemic chemotherapy during the trial.

What data supports the effectiveness of the drug ST-02 for treating urothelial carcinoma?

Research shows that gemcitabine, a component of ST-02, has been used successfully in treating bladder cancer, especially when other treatments have failed. Additionally, using chemotherapy drugs like gemcitabine directly in the urinary tract has shown potential benefits in controlling tumors. ^{1 2 3 4 5}

Is ST-02 (gemcitabine) safe for humans?

Gemcitabine, when used in the bladder for various types of bladder cancer, has been studied for safety. These studies generally show that it is safe for use in humans, with some patients experiencing mild side effects. ^{1 5 6 7 8}

How is the drug ST-02 different from other treatments for urothelial carcinoma?

ST-02 is unique because it is a mucoadhesive gemcitabine suspension designed for direct instillation into the pyelocaliceal system (part of the kidney), which may allow for targeted delivery and reduced systemic side effects compared to traditional systemic chemotherapy. ^{1 5 7 8 9}

What is the purpose of this trial?

The goal of this prospective clinical trial is to investigate the safety and efficacy of ST-02 (mucoadhesive gemcitabine suspension for pyelocaliceal instillation) to treat Upper Tract Urothelial Carcinoma (UTUC) in participants who have a low-grade tumor. The main questions this study aims to answer are: 1. Can ST-02 effectively eradicate UTUC by 3 months? 2. Is ST-02 safe for patients with UTUC? Participants in this study will receive ST-02, a new formulation with gemcitabine once weekly for six weeks. Gemcitabine is known to be an effective drug in treating urothelial carcinoma. This new formulation will be instilled directly into the upper urinary tract (renal pelvis) and will allow the chemotherapeutic to work locally for an extended period of time. The administration process will be retrograde (via a small catheter inserted up into the kidney, under anesthesia) or antegrade (via a nephrostomy, in the clinic) once weekly for six weeks. Safety and efficacy will be monitored for up to a year after the initial response assessment.

Research Team

Peter Black, MD

Principal Investigator

Vancouver Prostate Centre

Eligibility Criteria

This trial is for adults with low-grade, noninvasive Upper Tract Urothelial Carcinoma (UTUC) in the kidney's drainage system. Candidates must have a life expectancy over 12 months and at least one measurable tumor. Women of childbearing potential and men with partners of childbearing potential must use contraception.

Inclusion Criteria

I agree to use a condom for at least 48 hours after each treatment.

A life expectancy of greater than 12 months

No active untreated urinary tract infection (UTI) as confirmed by urine culture or urinalysis

Exclusion Criteria

Currently receiving another investigational agent or involved in a clinical trial with an investigational product within the past 30 days prior to Visit 1

I received BCG treatment for upper urinary tract cancer within the last 6 weeks.

I am not pregnant, planning a pregnancy, breastfeeding, or I use reliable contraception.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ST-02 once weekly for six weeks via retrograde or antegrade instillation

6 weeks

6 visits (in-person)

Primary Tumor Evaluation (PTE)

Evaluation of complete response (CR) at 3 months from the first instillation using ureteroscopy and cytology

3 months

1 visit (in-person)

Follow-up

Endoscopic monitoring of the upper tract with ureteroscopy every 3 months for up to 12 months after CR, with additional ST-02 instillation if no recurrence is noted

12 months

4 visits (in-person)

Treatment Details

Interventions

• ST-02

Trial Overview The study tests ST-02, a mucoadhesive gemcitabine suspension designed for direct application to UTUC. Participants will receive this treatment weekly for six weeks to see if it can eliminate UTUC within three months and assess its safety over a year.

Participant Groups

Group I: ST-02 Experimental Treatment 1 Intervention

ST-02 is a new gemcitabine formulation for instillation into the upper urinary tract. Eligible participants will be enrolled and receive ST-02 once weekly for six weeks in a retrograde or antegrade fashion at the discretion of the treating urologist.

ST-02 is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Gemcitabine for:

• Bladder cancer
• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemcitabine for:

• Ovarian cancer
• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer

Approved in Canada as Gemcitabine for:

• Ovarian cancer
• Breast cancer
• Pancreatic cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Findings from Research

Intravesical gemcitabine treatment after failure of first-line chemotherapy showed a significantly higher 2-year tumor-free survival rate of 70.8% compared to 45.8% for patients receiving original chemotherapy, indicating its efficacy in treating recurrent non-muscle-invasive bladder cancer.

The treatment was generally well tolerated, with only mild adverse effects reported, including one case of renal impairment in each of the gemcitabine groups, suggesting that while effective, renal function should be monitored during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the efficacy and safety of intravesical instillation with gemcitabine after first-line intravesical chemotherapy failure in the treatment of non-muscle-invasive bladder cancer]. Cao, M., Ma, CK., Ma, J., et al.[2022]

Gemcitabine (GEM) was administered to three patients with metastatic urothelial carcinoma, showing varied responses: one patient maintained stable disease after 9 cycles, while two others experienced progressive disease after 8 and 3 cycles, respectively.

Despite some cases of severe bone marrow suppression (grade 3 or 4) in two patients, GEM can be considered for patients with severe renal insufficiency and as maintenance therapy, although its efficacy may vary significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience with gemcitabine monotherapy in three patients with metastatic urothelial carcinoma]. Kyoda, Y., Kunishima, Y., Fukuta, F.[2022]

Topical instillation of Bacillus Calmette-Guérin (BCG) is recommended as a first-line treatment for upper urinary tract carcinoma in situ (CIS) after conservative management, based on retrospective studies.

The efficacy of adjuvant topical therapy, such as BCG or mitomycin C, after the endoscopic resection of Ta/T1 tumors remains unclear, with no studies showing significant improvements in survival or recurrence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upper urinary tract instillations in the treatment of urothelial carcinomas: a review of technical constraints and outcomes. Audenet, F., Traxer, O., Bensalah, K., et al.[2022]

Intravesical chemotherapy has proven effective for bladder cancer treatment, and there is growing interest in using similar agents as adjuvant therapy for upper urinary tract urothelial tumors, suggesting potential benefits for improved tumor control.

In a study involving 9 patients who received endoluminal instillation of epidoxorubicin after local excision of ureteral or renal pelvis tumors, the findings indicate a need for specific guidelines and surveillance protocols to optimize the use of topical chemotherapy in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoluminal instillation of epidoxorubicin as adjuvant treatment for upper urinary tract urothelial tumours. Ponchietti, R., Neri, B., Di Loro, F., et al.[2013]

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 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 study of 15 patients with non-muscle-invasive bladder cancer, a single high-concentration intravesical instillation of gemcitabine showed that systemic absorption is proportional to the extent of tumor resection, with peak plasma concentrations being lower than those seen with intravenous administration.

At a mean follow-up of 2 years, 60% of patients remained recurrence-free, and the treatment was well-tolerated, with toxicity not exceeding grade 2, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic absorption and pharmacokinetics of single-dose intravesical gemcitabine after transurethral resection of the bladder in non-muscle-invasive bladder cancer. Maffezzini, M., Campodonico, F., Puntoni, M., et al.[2022]

Intravesical gemcitabine instillation may significantly reduce the risk of recurrence and progression in patients with non-muscle invasive bladder cancer (NMIBC) compared to saline and mitomycin, based on a review of seven studies involving 1,222 participants.

While gemcitabine shows promise in improving outcomes for NMIBC, the safety profile regarding severe adverse events (grade III to V) compared to other treatments like mitomycin and BCG remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical gemcitabine for non-muscle invasive bladder cancer: An abridged Cochrane Review. Han, MA., Maisch, P., Jung, JH., et al.[2022]

A single postoperative instillation of gemcitabine (GEM) after transurethral resection (TUR) for non-muscle-invasive bladder cancer (NMIBC) did not show a significant improvement in recurrence-free survival (RFS) compared to placebo, with 12-month RFS rates of 77.7% for GEM and 75.3% for placebo.

The study involved 355 patients, with 328 receiving treatment, and was terminated early due to high RFS rates in both groups, suggesting that factors like continuous bladder irrigation and improved surgical techniques may have influenced outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single postoperative instillation of gemcitabine in patients with non-muscle-invasive transitional cell carcinoma of the bladder: a randomised, double-blind, placebo-controlled phase III multicentre study. Böhle, A., Leyh, H., Frei, C., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Evaluation of the efficacy and safety of intravesical instillation with gemcitabine after first-line intravesical chemotherapy failure in the treatment of non-muscle-invasive bladder cancer]. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

[Experience with gemcitabine monotherapy in three patients with metastatic urothelial carcinoma]. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Upper urinary tract instillations in the treatment of urothelial carcinomas: a review of technical constraints and outcomes. [2022]

4. Greece pubmed.ncbi.nlm.nih.gov

Endoluminal instillation of epidoxorubicin as adjuvant treatment for upper urinary tract urothelial tumours. [2013]

5. 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]

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

Systemic absorption and pharmacokinetics of single-dose intravesical gemcitabine after transurethral resection of the bladder in non-muscle-invasive bladder cancer. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Intravesical gemcitabine for non-muscle invasive bladder cancer: An abridged Cochrane Review. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Single postoperative instillation of gemcitabine in patients with non-muscle-invasive transitional cell carcinoma of the bladder: a randomised, double-blind, placebo-controlled phase III multicentre study. [2022]