PDT for Bladder Cancer

Recruiting at 21 trial locations

Overseen By Arkady Mandel, MD, PhD, DSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Theralase Technologies Inc.

Disqualifiers: Muscle invasive cancer, Metastatic cancer, Active hematuria, Active infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for bladder cancer patients who do not respond to or cannot tolerate standard therapy. The treatment uses a drug called Ruvidar® that is activated by a special light to kill cancer cells in the bladder.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it mentions that you cannot be on any prohibited therapies. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the treatment Ruvidar® (TLD-1433) for bladder cancer?

A study showed that photodynamic therapy (PDT) using TLD-1433 was tested in patients with bladder cancer that did not respond to previous treatments, suggesting it may be effective for this condition. ^{1 2 3 4 5}

Is photodynamic therapy (PDT) for bladder cancer safe?

Research shows that photodynamic therapy (PDT) for bladder cancer, including treatments using TLD-1433 and other photosensitizers, is generally safe. Studies have reported no serious treatment-related side effects, and any bladder irritation or volume loss was related to the light dose and tumor extent, but not severe. ^{2 3 4 5 6}

What makes the treatment Ruvidar® (TLD-1433) unique for bladder cancer?

Ruvidar® (TLD-1433) is unique because it uses photodynamic therapy (PDT), which involves a special drug activated by light to destroy cancer cells, specifically for patients whose bladder cancer does not respond to standard Bacillus Calmette-Guérin (BCG) treatment. ^{2 3 4 5 7}

Research Team

Girish Kulkarni, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults with non-muscle invasive bladder cancer who can't tolerate or haven't responded to BCG therapy. They must be able to hold the study drug in their bladder for at least 60 minutes, not have plans for a cystectomy, and women of childbearing age must use birth control or abstain from sex. People are excluded if they've had certain treatments recently, have active bleeding in urine, anesthesia risks, other cancers needing treatment (with some exceptions), or an active infection.

Inclusion Criteria

I cannot or do not want to undergo major bladder surgery.

Be willing and able to provide a written Informed Consent Form ("ICF") for the Study

Are available for the duration of the Study including follow-up (approximately 15 months)

Exclusion Criteria

Is pregnant or breastfeeding within the projected duration of Study II, starting with the screening visit through to two weeks following the second Ruvidar® (TLD-1433) instillation

Participated in a study with an investigational agent or device within 1 month from the first dose of current Study treatment

I don't have any health issues that would interfere with the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Primary Treatment

Participants receive the first intravesical PDT treatment with Ruvidar® (TLD-1433) at Day 0

1 day

1 visit (in-person)

Maintenance Treatment

Participants receive the second intravesical PDT treatment with Ruvidar® (TLD-1433) at Day 180

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 months

Multiple visits at Day 0, 7, 30, 60, 90, 180, 187, 210, 240, 270, 360, and 450

Treatment Details

Interventions

• Ruvidar® (TLD-1433) (Photosensitizer)

Trial Overview The trial tests Ruvidar® (TLD-1433) infused into the bladder followed by photodynamic therapy on patients with NMIBC who don’t respond to BCG treatment. It's an open-label phase II study across Canada and the US involving around 100-125 patients receiving two PDT treatments six months apart.

Participant Groups

Group I: 0.7 mg/cm^2 Ruvidar® (TLD-1433) Bladder infusion and Photodynamic Therapy Experimental Treatment 1 Intervention

A single instillation of Ruvidar® (TLD-1433) (at the therapeutic dose of 0.7 mg/cm\^2) will be infused intravesically into the bladder for approximately 60 minutes. PDT treatment is performed after Ruvidar® (TLD-1433) has been rinsed from the bladder. Two Study Treatments will be performed, a primary Study Treatment at Day 0 and a maintenance Study Treatment at Day 180.

Who Is Running the Clinical Trial?

Theralase Technologies Inc.

Lead Sponsor

Trials

1

Recruited

130+

Theralase® Technologies Inc.

Lead Sponsor

Trials

2

Recruited

130+

Theralase Inc.

Lead Sponsor

Trials

2

Recruited

130+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Pharma eMarket

Collaborator

Trials

1

Recruited

130+

Findings from Research

Photodynamic therapy using Radachlorin demonstrated a high recurrence-free rate of 90.9% at 12 months for patients with high-grade, nonmuscle invasive bladder cancer who were refractory or intolerant to standard bacillus Calmette-Guérin therapy.

The treatment was found to be safe, with no severe adverse effects reported, making it a viable option for patients who refuse radical cystectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of photodynamic therapy for recurrent, high grade nonmuscle invasive bladder cancer refractory or intolerant to bacille Calmette-Guérin immunotherapy. Lee, JY., Diaz, RR., Cho, KS., et al.[2022]

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 pilot study involving five patients with muscle-invasive bladder cancer, green light photodynamic therapy (PDT) using Photofrin was found to be safe, with no serious treatment-related complications or transmural bladder injury observed.

The level of acute bladder irritation and loss of bladder volume after treatment was influenced by the light dose and the extent of the tumor, indicating that careful dosing is important for minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Green light photodynamic therapy in the human bladder. Nseyo, UO., Merrill, DC., Lundahl, SL.[2007]

Photodynamic therapy (PDT) using the photosensitizer TLD-1433 was found to be safe and well-tolerated in a phase 1b study involving six patients with BCG-unresponsive non-muscle-invasive bladder cancer, with no serious adverse events reported.

Early efficacy results showed that two out of three patients treated at the therapeutic dose achieved a complete response at 180 days, suggesting that TLD-1433 PDT may be a promising treatment option that warrants further investigation in phase 2 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b Clinical Study of Intravesical Photodynamic Therapy in Patients with Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer. Kulkarni, GS., Lilge, L., Nesbitt, M., et al.[2022]

In a study of 153 patients with T1G3 bladder cancer, those treated with photodynamic diagnosis (PDD) during initial TUR-BT had a significantly lower recurrence rate of 29.9% compared to 56.6% in patients treated without PDD (P < 0.001).

PDD also detected additional carcinoma in situ in 35.4% of cases, suggesting it may improve initial tumor control and treatment effectiveness for aggressive bladder cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic diagnosis in patients with T1G3 bladder cancer: influence on recurrence rate. Stanislaus, P., Zaak, D., Stadler, T., et al.[2021]

References

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

Efficacy and safety of photodynamic therapy for recurrent, high grade nonmuscle invasive bladder cancer refractory or intolerant to bacille Calmette-Guérin immunotherapy. [2022]

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

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

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

Green light photodynamic therapy in the human bladder. [2007]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A Phase 1b Clinical Study of Intravesical Photodynamic Therapy in Patients with Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Photodynamic diagnosis in patients with T1G3 bladder cancer: influence on recurrence rate. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Transurethral Resection of Non-Muscle Invasive Bladder Tumors Combined with Fluorescence Diagnosis and Photodynamic Therapy with Chlorin e6-Type Photosensitizers. [2023]

7. England pubmed.ncbi.nlm.nih.gov

The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma. [2019]