Padeliporfin VTP Treatment for Unresectable Pancreatic Adenocarcinoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Combination Product: 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
Other Names:
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| Experimental: 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 |
Combination Product: 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
Other Names:
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Outcome Measures
Primary Outcome Measures
- Safety of endovascularly applied Padeliporfin VTP ablation [Day 30]
Safety of endovascularly applied Padeliporfin VTP ablation will be assessed using the CTCAE version 5.0. All adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) for being included in analyses.
- Determination of the Maximum Tolerated Light Dose (MTD) and/or Recommended Phase 2 light dose (RP2D) in Part A [Day 30]
MTD is defined as the dose level associated with <33% of DLT-evaluable patients experiencing a DLT. If the MTD is reached, the RP2D will be defined as MTD. If the MTD is not reached, the RP2D will be selected based on integrated evaluation of safety and clinical benefit for all dose levels tested.
Secondary Outcome Measures
- Descriptive features of treatment response to ablation in tumor tissue based on pre- and post -VTP CT scans [Day 2]
Rate of resectability and downstaging (as per NCCN Clinical Practice Guidelines V1, May 4, 2023)
- Tumor Response by CT scans [Day 30]
Based on CT scan according to RECIST 1.1
- Tumor Response by CT scans [Day 60]
Based on CT scan according to RECIST 1.1
Other Outcome Measures
- Exploratory endpoints [60 days]
Rate of resectability and downstaging will be evaluated by determining the percentage of patients who were initially deemed to have unresectable LA PDAC and following Padeliporfin VTP treatment, were subsequently deemed to have borderline resectable or resectable disease
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients 18 years of age and older
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Capable of giving written informed consent
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Patients with a diagnosis of Stage III pancreatic ductal adenocarcinoma, cytologically or histologically confirmed per American Joint Committee on Cancer (AJCC) staging criteria
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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)
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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
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Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors according to RECIST 1.1
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ECOG performance status </= 1
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Life expectancy at least 3 months
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No evidence of metastatic disease by CT scan chest abdomen and pelvis performed within 14 days prior to treatment
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Adequate Hematological, biochemical, and organ (kidney, liver, cardiac) function
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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.
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May have received prior neoadjuvant systemic therapy
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No prior external beam radiation therapy to the pancreas
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No comorbidities which would preclude access to the superior mesenteric artery by intravascular catheterization
Exclusion Criteria:
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Metastatic (stage IV) disease (including involvement of the colon, adrenals, or kidney, or radiographic evidence of peritoneal seeding or pulmonary metastases)
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SMA anatomical variants (SMA origin not from aorta)
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Previous radiotherapy treatment for pancreatic cancer
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Cystic component >= 25% the total volume of the tumor
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Ascites detected by CT, ultrasound (US) or MRI;
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Diagnosis of islet cell tumor, lymphoma, metastatic lesion, acinar cell (or other atypical pathologic malignancy)
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History of other malignancy requiring treatment in the past 2 years
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Unable to receive or previously intolerant of moderate and/or deep sedation
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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
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Pregnant and/or nursing
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Active infection, with the exception of resolving cholangitis
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Known hypersensitivity to iodine contrast
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Receipt of concurrent investigational therapy or within 30 days of protocol initiation
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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
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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
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Prohibited medication that could not be adjusted or discontinued prior to study treatment
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Patients with photosensitive skin diseases or porphyria
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Steba Biotech S.A.
- Impact biotech Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CLIN2301 PNCM101