Light Activated Drug Therapy for Urothelial Carcinoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Chemotherapy, Biologic therapy, Immunotherapy

Disqualifiers: Pregnancy, T4 tumors, Heart failure, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for urothelial carcinoma, a type of bladder cancer. The treatment uses a drug called WST11, activated by light during an endoscopy, to destroy cancer cells. Known as WST11-mediated vascular targeted phototherapy (VTP), this method aims to determine its safety for patients whose cancer has returned after previous treatments or who cannot undergo surgery. Suitable candidates for this trial have confirmed urothelial carcinoma in the kidney or ureter, have had unsuccessful endoscopic treatment, and cannot or do not want surgery. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you should not have received any systemic therapy (like chemotherapy or immunotherapy) within 4 weeks before treatment. If you are on anticoagulation therapy, it may be temporarily withheld if your doctor thinks it's safe.

What prior data suggests that this combination of WST11 and PDT is safe?

Research shows that WST11, used in a treatment called vascular-targeted phototherapy (VTP), may help treat urothelial carcinoma, a type of bladder cancer. Studies have found that this treatment is generally well-tolerated by patients, with most not experiencing severe side effects. In a trial for upper tract urothelial carcinoma, WST11 VTP proved safe for most patients.

Another study tested WST11 with photodynamic therapy (PDT) on animals like pigs and mice, and it was safe for them, suggesting potential safety for humans. Photodynamic therapy is already approved for some other types of cancer, which adds confidence in its safety.

Overall, while the current study phase will provide more information, earlier research suggests that WST11 VTP is likely safe for humans, with most side effects being manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for urothelial carcinoma, which typically involve surgery, chemotherapy, or immunotherapy, WST11 mediated vascular targeted phototherapy (VTP) offers a unique approach by using light activation to target tumors. This treatment works by activating the drug WST11 with light specifically at the tumor site, which helps to destroy cancerous tissue while sparing healthy tissue. Researchers are excited because this method could provide a less invasive option for patients who are not eligible for surgery or who have exhausted other treatments, potentially offering quicker recovery times and fewer side effects.

What evidence suggests that WST11 mediated vascular targeted phototherapy is effective for urothelial carcinoma?

Research has shown that WST11-mediated vascular targeted phototherapy (VTP), which participants in this trial will receive, holds promise for treating bladder cancer. Animal studies demonstrated that this treatment effectively targets and destroys cancer cells in the upper urinary tract. Additionally, trials for other cancers, such as prostate cancer, have found WST11-VTP to be safe and effective. This treatment uses a drug activated by light to destroy tumor cells, slowing cancer progression and improving survival rates in some studies. Although more research is needed in humans for bladder cancer, early results are encouraging. ^{1 4 6 7 8}

Who Is on the Research Team?

Jonathan Coleman, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with urothelial carcinoma in the kidney or ureter, who've had prior endoscopic treatment but still have cancer. They must be fit enough for the procedure (Karnofsky score ≥ 50%), able to pause anticoagulants if needed, and have good organ function. Pregnant women, those not using contraception, and patients with severe other diseases can't join.

Inclusion Criteria

I am on blood thinners, but my doctor thinks it's safe to stop them temporarily.

My cancer diagnosis of the ureter or renal pelvis was confirmed by tissue diagnosis.

My cancer came back after a previous endoscopic treatment.

Exclusion Criteria

Pregnant or breast-feeding women. Women of childbearing potential (WOCBP) must undergo a negative pregnancy test (either serum or urine) prior to study entry. Both sexes must use contraception while on study. WOCBP include: Any woman who has experienced menarche and who has not undergone surgical sterilization (hysterectomy, bilateral tubal ligation or oophorectomy) or who is not post-menopausal (defined as amenorrheic ≥12 consecutive months), Women on hormone replacement therapy with documented serum follicle stimulating hormone level > 35 mIU/ml, Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as intrauterine device or barrier methods to prevent pregnancy or are practicing abstinence or where the partner is sterile, T4 tumors with involvement of the bowel or major blood vessels, Any other medical or psychiatric comorbidities, including decompensated heart failure, unstable angina or coronary artery disease or severe pulmonary disease that, in the opinion of the study investigator, would make the patient a poor candidate for the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive WST11 phototherapy during endoscopy to treat tumors in the urinary collecting system

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Endoscopy
• WST11 mediated vascular targeted phototherapy (VTP)

Trial Overview The trial is testing WST11 mediated vascular targeted phototherapy (VTP) combined with endoscopy on tumors within the urinary system. WST11 is a drug activated by light during endoscopy to destroy tumor cells; this method has been used for other cancers before.

How Is the Trial Designed?

Group I: phototherapy with WST11 Experimental Treatment 2 Interventions

Patients with urothelial cancer that includes involvement of the upper urinary tract and have failed prior endoscopic treatment, refuse standard treatment, or are ineligible for curative surgical resection of the kidney or ureter will be offered WST11 VTP treatment to be provided at the time of scheduled endoscopic procedure. At the time of endoscopy, patients will be treated with VTP therapy applied to the site of the tumor.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Hexaminolevulinate (HAL) based photodynamic therapy (PDT) is a safe and technically feasible adjuvant treatment for patients with intermediate or high-risk bladder cancer, with no technical complications reported during the procedure.

In a study of 17 patients, 52.9% were tumor-free at 6 months post-treatment, indicating potential efficacy, although the percentage of patients remaining tumor-free decreased over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy of bladder cancer - a phase I study using hexaminolevulinate (HAL). Bader, MJ., Stepp, H., Beyer, W., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10265489/

Final Results of a Phase I Trial of WST-11 (TOOKAD ... The primary objective of this Phase 1 study was to identify the MTD of laser light fluence rate (mW/cm) of light exposure for VTP treatment of urothelial cancer ...

2. nature.com nature.com/articles/s41598-021-84184-y

Neoadjuvant vascular-targeted photodynamic therapy ... Neoadjuvant sbVTP delayed local and systemic progression, prolonged progression-free and overall survival, and reduced local recurrence.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022534716002421

Treatment Effects of WST11 Vascular Targeted ... WST11-VTP can be successfully and safely applied to the porcine upper urinary tract. Human xenograft lines of UTUC in a murine model are responsive to WST11-VTP ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/php.14048

Selectivity and anti‐tumor immune elevation by vascular‐ ... In the present study, we aimed to preclinically test the feasibility of WST11-VTP for treating tumors of the lower urinary tract, such as muscle ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4914469/

TREATMENT EFFECTS OF WST11 VASCULAR ... WST11-VTP of tumor bearing solid organs was found to be safe and effective in prostate cancer clinical trials. WST11-VTP may be uniquely suited ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA4513

ENLIGHTED phase 3 study: Interim results of efficacy and ... We report the interim analysis of efficacy and safety outcomes of Padeliporfin VTP for treatment of LG UTUC in ENLIGHTED, a Phase 3 trial (NCT04620239).

7. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/2421/723855/Abstract-2421-WST-11-vascular-targeted

Abstract 2421: WST-11 vascular-targeted photodynamic ... A phase 1 trial of VTP evaluating treatment of upper tract urothelial carcinoma (UTUC) showed an acceptable safety profile with strong potential.

8. auajournals.org auajournals.org/doi/pdf/10.1097/JU.0000000000003202

Final Results of a Phase I Trial of WST-11 (TOOKAD ... Conclusions: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing.