PDT for Bladder Cancer

Recruiting at 22 trial locations

Overseen By Arkady Mandel, MD, PhD, DSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Theralase Technologies Inc.

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

Compensation: Varies

Number of Visits: 2

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Ruvidar® (TLD-1433) for patients with a specific type of bladder cancer. It targets individuals whose cancer did not respond well to BCG therapy or who cannot tolerate it. The treatment involves two sessions of photodynamic therapy (PDT), where a special drug makes cancer cells sensitive to light. People with non-muscle invasive bladder cancer who have had trouble with BCG treatment might be a good fit for this trial. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important advancements in cancer treatment.

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 prior data suggests that this photodynamic therapy is safe for bladder cancer patients?

Research has shown that Ruvidar® (TLD-1433), used in photodynamic therapy (PDT), is generally safe for people with bladder cancer unresponsive to standard BCG treatment. In earlier studies, participants tolerated this treatment well and did not report major side effects.

The treatment involves introducing a light-sensitive drug into the bladder and activating it with light to target cancer cells. Studies indicate that this approach yielded good results without serious problems.

Although still under investigation, early findings suggest it is a promising option with manageable side effects. ^{1 2 3 4 5}

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

Unlike the standard treatments for bladder cancer, which often involve surgery or chemotherapy, Ruvidar® (TLD-1433) offers a novel approach through photodynamic therapy (PDT). This treatment involves infusing the medication directly into the bladder and using light to activate it, targeting cancer cells more precisely. Researchers are excited because this method aims to minimize damage to surrounding healthy tissue and potentially reduce side effects compared to traditional treatments. Additionally, the use of Ruvidar® (TLD-1433) as a photosensitizing agent is a unique mechanism that could enhance treatment efficacy and improve patient outcomes.

What evidence suggests that Ruvidar® (TLD-1433) might be an effective treatment for bladder cancer?

Research has shown that photodynamic therapy (PDT) with Ruvidar® (TLD-1433) could effectively treat bladder cancer unresponsive to BCG, a common treatment. In earlier studies, 62.5% of patients experienced a complete response, meaning their cancer was undetectable at some point during treatment. The lasting effect of this response was 45%. This suggests that Ruvidar® might be a viable option for those whose bladder cancer doesn't respond to other treatments. The therapy uses light to activate the drug, which then destroys cancer cells. These findings offer hope for patients seeking alternatives after BCG therapy fails. ^{1 2 3 6 7}

Who Is on the Research Team?

Girish Kulkarni, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ruvidar® (TLD-1433)

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.

How Is the Trial Designed?

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+

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) 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 pilot study involving 12 patients with non-muscle invasive bladder cancer, the combination of transurethral resection (TURB), fluorescence diagnosis (FD), and photodynamic therapy (PDT) resulted in 11 out of 12 patients remaining tumor-free after a median follow-up of 24 months, indicating high efficacy.

The treatment was found to be safe, with only one patient experiencing a recurrence that did not progress, suggesting that this approach could be a promising first-line option for managing superficial bladder tumors.

NCBI (Pubmed)

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. Kustov, AV., Smirnova, NL., Privalov, OA., et al.[2023]

In a study involving 76 female Fischer F344 rats with superficial bladder cancer, photodynamic therapy (PDT) using intravesical aminolaevulinic acid (ALA) significantly reduced tumor presence, with only 1 out of 12 rats showing carcinoma after treatment compared to 33 out of 40 in the control group.

Intravesical ALA was more effective than intravenous ALA in eradicating bladder carcinoma, demonstrating the potential of PDT as a promising alternative therapy for superficial bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of photodynamic therapy on rat urinary bladder with orthotopic urothelial carcinoma. Grönlund-Pakkanen, S., Wahlfors, J., Talja, M., et al.[2019]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9257636/

A Phase 1b Clinical Study of Intravesical Photodynamic ... Photodynamic therapy with TLD-1433 appears to be safe and effective for the treatment of bacillus Calmette-Guérin (BCG)-unresponsive bladder cancer.

2. renalandurologynews.com renalandurologynews.com/reports/bladder-cancer-nmibc-bcg-unresponsive-tld1433-photodynamic-therapy/

TLD-1433 Photodynamic Therapy Shows Promise for BCG ... “PDT yielded a CR (complete response) at any time point of 62.5% in an interim analysis of 64 patients with durability of response of 45% in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03945162

NCT03945162 | Intravesical Photodynamic Therapy ("PDT ... The Study will consist of approximately 100 to 125 patients who will undergo two (2) PDT treatments employing 0.70 mg/cm^2 of Ruvidar® (TLD-1433) at Day 0 and ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.528

A phase II clinical study of intravesical photo dynamic ... Conclusions: The interim data support that treatment with Photo Dynamic Therapy provides a viable treatment option for patients with BCG ...

5. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/irb201049

CLINICAL TRIAL / NCT03945162 The Study will consist of approximately 100 to 125 patients who will undergo two (2) PDT treatments employing 0.70 mg/cm^2 of Ruvidar® (TLD-1433) at Day 0 and ...

6. onclive.com onclive.com/view/ruvidar-demonstrates-potential-for-durable-responses-in-non-muscle-invasive-bladder-cancer

Ruvidar Demonstrates Potential for Durable Responses in ... Treatment with TLD-1433 led to 6-, 12-, and 15-month CR rates of 54%, 38%, and 37%, respectively, in patients with non–muscle invasive bladder ...

7. auajournals.org auajournals.org/doi/10.1097/01.JU.0001109848.08748.9e.13

PD12-13 INTERIM ANALYSIS OF LIGHT-ACTIVATED TLD ... We report on the interim results of a Phase II clinical study of a light-activated small molecule, TLD-1433, in patients with BCG-Unresponsive NMIBC Carcinoma ...