Padeliporfin VTP for Bladder Cancer

(UCM301 Trial)

Recruiting at 29 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

Trial Summary

What is the purpose of this trial?

This is a phase 3, open label, single arm study of padeliporfin in the treatment of Upper Tract Urothelial Carcinoma (UTUC). The ENLIGHTED study will recruit patients with low-grade non-invasive upper tract urothelial carcinoma in either the kidney or the ureter. Patients will be treated with padeliporfin VTP in two phases: an Induction Treatment Phase and a Maintenance Treatment Phase and will be followed up for up to an additional 48 months in the long term (non intervention) follow up phase with the specific duration depending on the patient's response to treatment

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.

What data supports the effectiveness of the treatment Padeliporfin VTP for bladder cancer?

Research shows that Padeliporfin VTP, a type of photodynamic therapy (a treatment using light-sensitive drugs and a light source to destroy cancer cells), has been effective in treating other urologic cancers by specifically targeting and destroying tumor cells. This suggests potential for its use in bladder cancer treatment. ^{1 2 3 4 5}

Is Padeliporfin VTP generally safe for humans?

A Phase I trial of Padeliporfin VTP (also known as WST-11 or TOOKAD Soluble) for upper tract urothelial carcinoma evaluated its safety and found it to be a promising treatment with therapeutic efficacy, suggesting it is generally safe for use in humans. ^{2 3 5 6 7}

How is the treatment Padeliporfin VTP unique for bladder cancer?

Padeliporfin VTP is unique because it uses a special light-activated process called photodynamic therapy (PDT) to target and destroy cancer cells in the bladder, making it a non-invasive option compared to traditional treatments. This therapy specifically targets blood vessels in the tumor, which helps to minimize damage to surrounding healthy tissue. ^{2 3 4 5 7}

Research Team

Vitaly Margulis

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

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

Photodynamic therapy of bladder cancer - a phase I study using hexaminolevulinate (HAL). [2013]

2. United States 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. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies. [2021]

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

Transferrin-conjugated liposome targeting of photosensitizer AlPcS4 to rat bladder carcinoma cells. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Combined chemotherapeutic and photodynamic treatment on human bladder cells by hematoporphyrin-platinum(II) conjugates. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of 120W high performance system greenlight laser vaporization for non-muscle-invasive bladder cancer. [2013]

7. Japan 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]. [2013]