Padeliporfin VTP for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Eyal Morag, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Impact Biotech Ltd

Must not be taking: VEGF-targeted therapy

Disqualifiers: Metastatic disease, SMA variants, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

30 Participants Needed

Trial Summary

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 certain prohibited medications need to be adjusted or discontinued before 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 pancreatic cancer?

Research shows that similar treatments using photosensitizers like verteporfin have been effective in killing pancreatic cancer cells in laboratory settings. Additionally, Padeliporfin VTP has shown promise in treating localized prostate cancer, suggesting potential for effectiveness in other cancers. ^{1 2 3 4 5}

What makes the treatment Padeliporfin VTP unique for pancreatic cancer?

Padeliporfin VTP is unique because it uses a light-activated drug to target blood vessels in the tumor, which is different from traditional chemotherapy or surgery. This method, known as vascular-targeted photodynamic therapy, is minimally invasive and can be performed in outpatient settings, offering a novel approach for treating localized cancers. ^{1 2 6 7 8}

What is the purpose of this trial?

This is a prospective, multicenter, non-randomized, open label light dose escalation phase I trial to evaluate the safety and preliminary efficacy of Padeliporfin vascular targeted photodynamic therapy (VTP) applied via endovascular fiber placement within a dilatation catheter, through the superior mesenteric artery (SMA) in patients with stage III, locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC). The investigators will evaluate safety and preliminary efficacy of Padeliporfin VTP administered endovascularly using light dose escalation.

Research Team

Nadine Abi-Jaoudeh, MD

Principal Investigator

University of California, Irvine

Eligibility Criteria

This trial is for adults over 18 with Stage III pancreatic ductal adenocarcinoma that can't be surgically removed. Participants must have a life expectancy of at least 3 months, good performance status (able to carry out daily activities), and no metastatic disease. They should also have adequate blood counts and organ function.

Inclusion Criteria

My blood clotting time is normal or managed with medication.

I may have had treatment before surgery to shrink my tumor.

Capable of giving written informed consent

Exclusion Criteria

I have been treated for another cancer within the last 2 years.

I haven't had chemotherapy or VEGF-targeted therapy in the last 30 days.

Pregnant and/or nursing

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part A

Light dose escalation with single dose of Padeliporfin at light laser doses of 200, 400, and 600 mW/cm for 10 minutes

4 weeks

Multiple visits for dose escalation

Treatment - Part B

Dose expansion at MTD/RP2D dose level to further assess safety, tolerability, and treatment effect

4 weeks

Multiple visits for treatment assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Follow-up visits at Day 30 and Day 60

Treatment Details

Interventions

• Padeliporfin VTP

Trial Overview The trial tests Padeliporfin VTP therapy, which involves injecting a drug into the bloodstream and activating it with light inside the pancreas through an artery. The study aims to find safe doses and see how well it works against advanced pancreatic cancer.

Participant Groups

Group I: Part B Experimental Treatment 1 Intervention

will be a dose expansion part at MTD/RP2D dose level identified in Part A to further assess the safety, tolerability, and treatment effect of the MTD and/ or RP2D

Group II: Part A Experimental Treatment 1 Intervention

will be a monotherapy light dose escalation with single dose of Padeliporfin at light laser doses of 200, 400 and 600 mW/cm for 10 minutes. Part A will proceed with light dose escalation and will continue until the maximum tolerated light dose (MTD) and/or recommended phase 2 dose (RP2D) is defined.

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?

Impact Biotech Ltd

Lead Sponsor

Trials

2

Recruited

70+

Steba Biotech S.A.

Lead Sponsor

Trials

17

Recruited

1,300+

Impact biotech Ltd.

Collaborator

Trials

2

Recruited

70+

Findings from Research

Vascular targeted photochemotherapy (VTP) using padoporfin and padeliporfin is a promising, minimally invasive treatment for localized prostate cancer, allowing for outpatient procedures.

Clinical trials indicate that VTP is effective for focal treatment of prostate cancer, and future developments aim to standardize this method with real-time feedback protocols and cost-effectiveness analyses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight. Bugaj, AM.[2020]

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) using verteporfin was found to be more effective than sodium porfimer in inducing cell death in pancreatic cancer cells, requiring 60 times lower concentration for similar effects.

The efficacy of PDT was shown to be independent of the inflammatory microenvironment created by activated stromal cells, indicating that PDT could be a reliable treatment option even in the presence of tumor-associated inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Verteporfin- and sodium porfimer-mediated photodynamic therapy enhances pancreatic cancer cell death without activating stromal cells in the microenvironment. Lu, J., Roy, B., Anderson, M., et al.[2020]

Verteporfin, a novel photosensitizer, demonstrated a safety profile similar to meso-tetrahydroxyphenylchlorin (mTHPC) in treating pancreatic cancer, with safe light doses identified that produced necrotic lesions without significant damage to surrounding tissues.

The drug has a short elimination half-life of 4-5 hours and a shorter drug-light interval, making it a promising candidate for Phase I clinical studies in pancreatic cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Photodynamic therapy using verteporfin photosensitization in the pancreas and surrounding tissues in the Syrian golden hamster. Ayaru, L., Wittmann, J., Macrobert, AJ., et al.[2022]

Deuteporfin, a novel photosensitizer, shows promise as a tracer agent for detecting lymphatic metastases in pancreatic cancer, demonstrating selective enrichment in cancerous tissues compared to normal tissues in a xenograft model.

The study found that deuteporfin can be administered intravenously, allowing for rapid accumulation in pancreatic and lymphatic tissues, making it a potentially effective tool for surgical applications in pancreatic cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the role of the photosensitizer, deuteporfin, in the detection of lymphatic metastases in a pancreatic cancer xenograft model. Yu, X., Li, H., Fu, D., et al.[2020]

Five new phosphorus(V) porphyrins were developed, showing good water-solubility and promising photophysical properties for use in phototherapy.

Two of these compounds demonstrated strong photocytotoxic effects against esophageal cancer cell lines, with IC50 values comparable to the established treatment mTHPC, indicating their potential as effective agents in photodynamic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT. Ryan, AA., Ebrahim, MM., Petitdemange, R., et al.[2014]

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]

EUS-guided verteporfin photodynamic therapy (PDT) was found to be feasible and safe for ablating locally advanced pancreatic cancer (LAPC), with no adverse events reported during or after the procedure in a pilot study of 8 patients.

The treatment resulted in tumor necrosis visible within 48 hours in 5 out of 8 patients, indicating its potential effectiveness as a minimally invasive option for patients with nonresectable LAPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EUS-guided verteporfin photodynamic therapy for pancreatic cancer. Hanada, Y., Pereira, SP., Pogue, B., et al.[2023]

References

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

Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight. [2020]

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

Verteporfin- and sodium porfimer-mediated photodynamic therapy enhances pancreatic cancer cell death without activating stromal cells in the microenvironment. [2020]

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

Photodynamic therapy using verteporfin photosensitization in the pancreas and surrounding tissues in the Syrian golden hamster. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Characterization of the role of the photosensitizer, deuteporfin, in the detection of lymphatic metastases in a pancreatic cancer xenograft model. [2020]

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

Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT. [2014]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

EUS-guided verteporfin photodynamic therapy for pancreatic cancer. [2023]