Padeliporfin VTP Treatment for Unresectable Pancreatic Adenocarcinoma

NCT ID: NCT05919238

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-15
• Study Completion Date: 2026-10-30

Brief Summary

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.

Detailed Description

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) with SMA solid tumor encasement >180°. The investigators will evaluate safety and preliminary efficacy of Padeliporfin VTP administered endovascularly using light dose escalation.

Study Intervention: Patients enrolled in the study will undergo endovascular VTP, using Padeliporfin (WST-11) activated via endovascular fiber placement through the SMA, with intravenous administration of Padeliporfin at a fixed dose of 4 mg/kg of padeliporfin di-potassium, followed by total of 10 min illumination at 753 nm.

For light dose escalation (Part A), a 3+3 dose-escalation schema will be used. In a subsequent expansion phase (Part B), the optimal light dose as per light dose escalation, will be used in an additional cohort of patients to further evaluate preliminary efficacy.

Conditions

Locally Advanced Unresectable Pancreatic Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A

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.

Group Type: EXPERIMENTAL

Padeliporfin Vascular Targeted Photodynamic (VTP) therapy

Intervention Type: COMBINATION_PRODUCT

The laser light fiber with inflatable balloon to dam SMA blood flow during light illumination will be placed by an Interventional Radiologist in the SMA via a transfemoral artery approach. The balloon will be inflated to impede blood flow for total of 10 minutes during light illumination

Part B

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 Type: EXPERIMENTAL

Padeliporfin Vascular Targeted Photodynamic (VTP) therapy

Intervention Type: COMBINATION_PRODUCT

The laser light fiber with inflatable balloon to dam SMA blood flow during light illumination will be placed by an Interventional Radiologist in the SMA via a transfemoral artery approach. The balloon will be inflated to impede blood flow for total of 10 minutes during light illumination

Interventions

Padeliporfin Vascular Targeted Photodynamic (VTP) therapy

The laser light fiber with inflatable balloon to dam SMA blood flow during light illumination will be placed by an Interventional Radiologist in the SMA via a transfemoral artery approach. The balloon will be inflated to impede blood flow for total of 10 minutes during light illumination

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Padeliporfin VTP

Eligibility Criteria

Inclusion Criteria

1. Patients 18 years of age and older

2. Capable of giving written informed consent

3. Patients with a diagnosis of Stage III pancreatic ductal adenocarcinoma, cytologically or histologically confirmed per American Joint Committee on Cancer (AJCC) staging criteria

4. Patient has a unresectable tumor, evaluated as Stage III according to National Comprehensive Cancer Network (NCCN) guidelines resectability criteria, based on radiographic imaging or exploratory surgery as a locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC)

5. Patients with LA PDAC located in the head/uncinate process of the pancreas, with SMA encasement ˃180° for a total proximal SMA encasement length up to 3cm

6. Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors according to RECIST 1.1

7. ECOG performance status </= 1

8. Life expectancy at least 3 months

9. No evidence of metastatic disease by CT scan chest abdomen and pelvis performed within 14 days prior to treatment

10. Adequate Hematological, biochemical, and organ (kidney, liver, cardiac) function

11. International normalized ratio (INR) <1.5 unless the patient is receiving anticoagulation therapy, in which case a therapeutic INR is acceptable. Anticoagulation therapy with low-molecular-weight heparin or warfarin, whether medically indicated, is permitted.

12. May have received prior neoadjuvant systemic therapy

13. No prior external beam radiation therapy to the pancreas

14. No comorbidities which would preclude access to the superior mesenteric artery by intravascular catheterization

Exclusion Criteria

1. Metastatic (stage IV) disease (including involvement of the colon, adrenals, or kidney, or radiographic evidence of peritoneal seeding or pulmonary metastases)

2. SMA anatomical variants (SMA origin not from aorta)

3. Previous radiotherapy treatment for pancreatic cancer

4. Cystic component >= 25% the total volume of the tumor

5. Ascites detected by CT, ultrasound (US) or MRI;

6. Diagnosis of islet cell tumor, lymphoma, metastatic lesion, acinar cell (or other atypical pathologic malignancy)

7. History of other malignancy requiring treatment in the past 2 years

8. Unable to receive or previously intolerant of moderate and/or deep sedation

9. Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, and participate in the study or that is likely to interfere with the interpretation of the results

10. Pregnant and/or nursing

11. Active infection, with the exception of resolving cholangitis

12. Known hypersensitivity to iodine contrast

13. Receipt of concurrent investigational therapy or within 30 days of protocol initiation

14. 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

15. Systemic chemotherapy treatment within less than 30 days prior to planned VTP or/and for VEGF-targeted therapy within less than 2 months prior to planned VTP treatment

16. Prohibited medication that could not be adjusted or discontinued prior to study treatment

17. Patients with photosensitive skin diseases or porphyria

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Impact Biotech Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadine Abi-Jaoudeh, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Irvine

Locations

City of Hope

Duarte, California, United States

Site Status: RECRUITING

University of California Irvine

Irvine, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Eyal Morag, MD

Role: CONTACT

eyal.morag@impactbiotech.com

+972 54 2056619

Facility Contacts

Jonathan Kessler, MD

Role: primary

Nadine Abi-Jaoudeh, MD

Role: primary

Other Identifiers

CLIN2301 PNCM101

Identifier Type: -

Identifier Source: org_study_id