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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety of a combination of the study drug called WST11 and PDT. Photodynamic therapy (PDT) is a type of ablation therapy (treatment which destroys tumor cells) which has been previously approved for the treatment of patients with other cancers. It works by using a drug that is given through the vein and then is activated in the tumor by light administered during endoscopy, which results in destruction of the cancer cells.

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 data supports the effectiveness of this treatment for urothelial carcinoma?

Research in mouse models shows that vascular-targeted photodynamic therapy (VTP) can significantly reduce tumor size and lower the chances of cancer spreading, while also improving survival rates. This suggests that VTP, when used before surgery, might be an effective treatment for urothelial carcinoma. ^{1 2 3 4 5}

Is vascular targeted photodynamic therapy (VTP) safe for humans?

Vascular targeted photodynamic therapy (VTP) has been studied for safety in humans, particularly in treating prostate cancer, and has shown medium-term tolerability. While specific safety data for urothelial carcinoma is limited, the treatment has been generally well-tolerated in other conditions. ^{1 2 3 4 6}

What makes WST11 mediated vascular targeted phototherapy (VTP) unique for treating urothelial carcinoma?

WST11 mediated vascular targeted phototherapy (VTP) is unique because it uses light to activate a drug that specifically targets the blood vessels feeding the tumor, which can help reduce tumor size and prevent recurrence by enhancing the body's immune response. This approach is different from traditional treatments that may not specifically target tumor vasculature or involve light activation. ^{1 2 3 5 7}

Research Team

Jonathan Coleman, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Effectiveness of the combination of vascular targeted photodynamic therapy and anti-cytotoxic T-lymphocyte-associated antigen 4 in a preclinical mouse model of urothelial carcinoma. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant vascular-targeted photodynamic therapy improves survival and reduces recurrence and progression in a mouse model of urothelial cancer. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Novel theranostic nanoporphyrins for photodynamic diagnosis and trimodal therapy for bladder cancer. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Enhanced chemo-photodynamic therapy of an enzyme-responsive prodrug in bladder cancer patient-derived xenograft models. [2022]

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

Medium-term Follow-up of Vascular-targeted Photodynamic Therapy of Localized Prostate Cancer Using TOOKAD Soluble WST-11 (Phase II Trials). [2020]

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

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