Padeliporfin VTP for Bladder Cancer

(UCM301 Trial)

Recruiting at 30 trial locations

Overseen By Eyal Morag, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Steba Biotech S.A.

Must not be taking: VEGF-targeted therapy

Disqualifiers: High-grade carcinoma, Invasive T2, 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: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called padeliporfin VTP for low-grade, non-invasive upper tract urothelial carcinoma, a type of bladder cancer in the kidneys or ureters. The goal is to evaluate the treatment's effectiveness in managing the cancer over time. The trial includes an initial treatment phase, followed by ongoing maintenance treatments for those who need it. Suitable candidates have bladder cancer that hasn't spread deeply or become aggressive and should not have had recent chemotherapy. As a Phase 3 trial, this is the final step before FDA approval, providing patients an opportunity to access a potentially effective treatment early.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that any prohibited medication should be adjusted or discontinued before starting the study treatment. It's best to discuss your current medications with the study team to see if any changes are needed.

Is there any evidence suggesting that padeliporfin VTP is likely to be safe for humans?

Research has shown that padeliporfin VTP is a promising and safe treatment for low-grade upper tract urothelial cancer. Earlier studies indicate that this treatment can effectively target the cancer while preserving kidney function. Interim results emphasize its safety, with most patients responding well to the therapy.

One study found that many patients experienced either a complete or partial response within 30 days of treatment, suggesting that padeliporfin VTP is generally well-tolerated. While some patients required a second treatment, the overall response was positive, and serious side effects were not commonly reported.

Overall, the evidence suggests that padeliporfin VTP is a safe option for patients with this type of cancer. ^{1 2 3 4 5}

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

Padeliporfin VTP is unique because it uses a light-activated drug to specifically target and destroy cancer cells in the bladder. Unlike traditional treatments like surgery or chemotherapy, which can affect both healthy and cancerous tissues, this method offers precision by activating only in the presence of a specific wavelength of light. Researchers are excited about this treatment because it minimizes damage to healthy tissues, potentially leading to fewer side effects and improved quality of life for patients with bladder cancer.

What evidence suggests that padeliporfin VTP might be an effective treatment for bladder cancer?

Research has shown that padeliporfin VTP, the treatment under study in this trial, holds promise for treating upper tract urothelial carcinoma (UTUC), a type of cancer. One study found that 94% of patients responded well to the treatment. Half of these patients experienced complete tumor disappearance, while the other half saw tumor reduction. Even patients requiring a second treatment achieved positive results. These studies suggest that padeliporfin VTP can effectively reduce or eliminate tumors in UTUC. The treatment has consistently proven safe and effective in various trials. ^{1 2 3 6 7}

Who Is on the Research Team?

Vitaly Margulis

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

The ENLIGHTED study is for adults with low-grade, non-invasive cancer in the kidney or ureter. Participants should have good physical function, specific tumor sizes and locations, normal blood counts and organ functions. Excluded are those with invasive cancers within 2 years, recent BCG/chemotherapy treatments, severe other diseases or heavy smoking habits, current high-grade bladder cancer or CIS in the upper tract.

Inclusion Criteria

My kidney function, measured by eGFR, is at least 30 ml/min.

Able to understand and provide written informed consent and willing to comply with all tests and procedures associated with the study

Total serum bilirubin <3 mg/dL

Exclusion Criteria

I have a skin condition that worsens with light exposure.

I am not willing to use birth control during and for 3 months after treatment.

I have or had early-stage cancer in my upper urinary tract.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Patients undergo 1-3 padeliporfin VTP treatments provided 4 weeks apart to achieve Complete Response (CR) in the involved ipsilateral tract system.

4-12 weeks

1-3 visits (in-person)

Maintenance Treatment

Patients achieving CR in the induction phase are followed for 12 months to assess response duration and safety, with repeated VTP treatments for treatable tumor recurrence.

12 months

Regular visits as needed for maintenance treatment

Long Term Follow-up

Patients are monitored for disease-related outcomes and VTP treatment-related adverse events for up to 48 months, with assessments at 18, 24 months, and annually thereafter.

48 months

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Padeliporfin VTP

Trial Overview This phase 3 trial tests padeliporfin VTP on patients with Upper Tract Urothelial Carcinoma (UTUC). It involves an Induction Treatment Phase followed by a Maintenance Treatment Phase. Patients will be monitored up to four additional years post-treatment to assess long-term effects of this single-arm intervention.

How Is the Trial Designed?

Group I: padeliporfin VTP Experimental Treatment 1 Intervention

Induction Treatment phase:1-3 padeliporfin VTP treatments provided 4 weeks (28 +/-3 days) apart. Maintenance Treatment Phase: Repeated maintenance VTP treatments during this period will be provided for patients who show evidence of tumor recurrence that is deemed treatable.

Padeliporfin VTP is already approved in European Union for the following indications:

Approved in European Union as Tookad for:

• Low-risk prostate cancer
• Upper tract urothelial carcinoma (UTUC)

Who Is Running the Clinical Trial?

Steba Biotech S.A.

Lead Sponsor

Trials

17

Recruited

1,300+

ICON plc

Industry Sponsor

Trials

88

Recruited

28,900+

Dr. Steve Cutler

ICON plc

Chief Executive Officer since 2017

PhD from the University of Sydney, MBA from the University of Birmingham

Dr. Greg Licholai

ICON plc

Chief Medical Officer since 2023

Degrees from Harvard Business School, Yale School of Medicine, Columbia University, and Boston College

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

PrimeVigilance

Industry Sponsor

Trials

7

Recruited

300+

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]

Photodynamic therapy (PDT) is gaining renewed interest in treating urological cancers due to advancements in understanding cancer biology and the development of better photosensitizers.

Vascular-targeted PDT (VTP) using padeliporfin has shown tumor-specific effectiveness, making it a promising option for managing urologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies. Nogueira, L., Tracey, AT., Alvim, R., et al.[2021]

In a Phase I trial involving 19 patients with upper tract urothelial carcinoma, vascular-targeted photodynamic therapy using the agent WST-11 showed a high initial treatment response rate of 94%, with 50% achieving complete response and 44% partial response within 30 days.

The therapy demonstrated an acceptable safety profile, with transient side effects like flank pain and hematuria, and no significant long-term complications such as ureteral strictures, indicating its potential as a kidney-sparing treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma. Yip, W., Sjoberg, DD., Nogueira, LM., et al.[2023]

The study identified a promising water-soluble porphyrin-platinum complex that combines the effects of cisplatin and photodynamic therapy, showing enhanced cytotoxicity against bladder cancer cells compared to traditional treatments.

This compound demonstrated a synergistic effect, meaning it worked better together than the individual drugs alone, suggesting a new potential strategy for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined chemotherapeutic and photodynamic treatment on human bladder cells by hematoporphyrin-platinum(II) conjugates. Lottner, C., Knuechel, R., Bernhardt, G., et al.[2019]

Intravesical administration of Cis-Diamminedichloroplatinum (DDP) in dogs showed minimal local toxicity and no significant systemic toxicity, making it a potentially safe option for treating superficial bladder cancers.

The study measured bladder tissue platinum concentrations, which were significantly elevated after DDP retention, indicating effective local delivery of the drug, but further research is needed to assess the long-term effects of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fundamental studies on intravesical instillation of cis-diamminedichloroplatinum for treatment of urinary bladder tumors. I: On the effects of intravesical instillation of cis-diamminedichloroplatinum in normal beagle dogs]. Hirao, Y., Iwai, A., Yoshie, T., et al.[2013]

Transferrin-conjugated liposomes (Tf-Lip-AlPcS4) significantly increased the accumulation of the photosensitizer aluminum phthalocyanine tetrasulfonate (AlPcS4) in bladder cancer cells compared to unconjugated liposomes, achieving levels of 384.1 microM versus just 3.7 microM, indicating effective tumor-selective targeting.

In an orthotopic rat bladder tumor model, Tf-Lip-AlPcS4 demonstrated a strong selective accumulation in tumor tissue with a mean fluorescence of 77.9 units, while free AlPcS4 showed nonselective distribution, suggesting that this targeting strategy enhances the efficacy of photodynamic therapy for superficial bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transferrin-conjugated liposome targeting of photosensitizer AlPcS4 to rat bladder carcinoma cells. Derycke, AS., Kamuhabwa, A., Gijsens, A., et al.[2022]

The 120W potassium-titanyl-phosphate (KTP) laser vaporization is a safe and effective treatment for non-muscle invasive bladder cancer, showing a lower recurrence rate compared to standard transurethral resection of bladder tumor (TUR-BT) in a study of 158 patients.

Patients treated with KTP laser experienced fewer specific side effects associated with TUR-BT, such as obturator nerve reflex and shorter catheterization time, making it a preferable option, especially for those on anticoagulation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of 120W high performance system greenlight laser vaporization for non-muscle-invasive bladder cancer. Tao, W., Yang, D., Shan, Y., 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 ... In evaluating efficacy, VTP demonstrated tumor response in the majority (94%) of patients, with CR seen in half of patients after one treatment. Complete ...

2. urotoday.com urotoday.com/conference-highlights/asco-2024/asco-2024-upper-tract-urothelial-carcinoma/152519-asco-2024-enlighted-phase-3-study-efficacy-and-safety-of-padeliporfin-vascular-targeted-photodynamic-therapy-vtp-for-treatment-of-low-grade-upper-tract-urothelial-cancer-lg-utuc.html

ASCO 2024: ENLIGHTED Phase 3 Study: Efficacy and ... The response rate at 30 days was 94% (50% complete response, 44% partial response). Eight patients received a second VTP treatment, resulting in a final ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36724067/

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble ... The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final ...

4. impactbiotech.com impactbiotech.com/impact-biotech-announces-new-data-presentations-at-aua-2025-highlighting-safety-and-efficacy-of-padeliporfin-vtp/

ImPact Biotech Announces New Data Presentations at ... ImPact Biotech Announces New Data Presentations at AUA 2025 Highlighting Safety and Efficacy of Padeliporfin VTP. Company to present updated ...

5. urotoday.com urotoday.com/conference-highlights/aua-2025/aua-2025-upper-tract-urothelial-carcinoma/160037-aua-2025-efficacy-and-safety-of-padeliporfin-vascular-targeted-photodynamic-therapy-for-treatment-of-low-grade-upper-tract-urothelial-cancer-enlighted-phase-3-study.html

AUA 2025: Efficacy and Safety of Padeliporfin Vascular ... Padeliporfin VTP has demonstrated safety and efficacy for upper tract urothelial cancer treatment in a phase 1 study.

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

Selectivity and anti‐tumor immune elevation by vascular‐ ... These results suggest that VTP can selectively ablate malignant tumors in the bladder and promote a robust anti-tumor response in a mouse model ...

7. targetedonc.com targetedonc.com/view/padeliporfin-vtp-shows-promise-for-low-grade-upper-tract-urothelial-cancer

Padeliporfin VTP Shows Promise for Low-Grade Upper ... Interim results reveal padeliporfin VTP therapy as a promising, safe treatment for low-grade upper tract urothelial cancer, preserving kidney function.