Early Feasibility Clinical Investigation to Assess YntraDose™ as a Neoadjuvant Treatment for LA-PDAC

The study is a multicentre, open-label, prospective, early feasibility clinical investigation to assess the safety, tolerability and feasibility of YntraDose™ treatment following percutaneous administration under Ultrasound/CT guidance.

The investigational device is YntraDose™, which is a locoregional therapy device used for percutaneous radio-ablation of solid tumours delivering targeted radiation using Y-90 microspheres injected directly into the tumour site, within a glue matrix holding the Y-90 microspheres in place. The product is designed for single use.

YntraDose™ is indicated as a neoadjuvant therapy and add-on treatment to first-line standard of care therapy in patients with unresectable LA-PDAC. The aim of YntraDose™ development is to combine it with chemotherapy standard of care (FOLFIRINOX or gemcitabine/nab-paclitaxel). Combining systemic chemotherapy with radiotherapy for local disease control, may improve time to progression of local disease, pain control, performance status, and quality of survival, and in a neoadjuvant setting may convert tumours to resectability.

YntraDose™ will be administered intratumorally and percutaneously into the pancreas under ultrasound/CT guidance. The Y-90 microspheres have been designed to deliver a localized distribution of beta radiation within the target tumour. The radiation from these particles causes direct damage to cancer cell DNA, which renders them incapable of further cell division and proliferation, leading to tumour shrinkage. The glue matrix is a hydrogel that polymerizes in the site of implantation and serves to retain the Y 90 radioactive microspheres in-situ facilitating the effect of radioactive microspheres in the tumoural tissue only.

Ten (10) patients with unresectable locally advanced pancreatic ductal adenocarcinoma meeting the eligibility criteria will be recruited into the clinical investigation.

Inclusion criteria

(Main):

• Histologically or cytologically proven Pancreatic Adenocarcinoma.
• Stage of disease defined as unresectable Locally Advanced Pancreatic Cancer.
• No prior radiotherapy for pancreatic cancer.
• Target tumour with a minimum diameter of 2.6 cm and a volume of from 9 to 34 ml.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patient has acceptable hematological parameters including white and red blood counts, liver and renal function that makes them suitable to receive SoC chemotherapy as per local clinical practice.
• Life expectancy of ≥6 months at screening.

Exclusion criteria

(Main):

• Evidence of distant metastases based on the restaging process after two months of induction chemotherapy identified using CT/MRI/18 FDG PET assessment.
• Evidence of switch from unresectable status to resectable status of disease after two months of induction chemotherapy.
• More than one primary lesion, if one of the primary lesions is not a good candidate for debulking with YntraDose™, due to clinical reasons and/or decision made by the local MDTB.
• ECOG is higher than 1.
• History of malignancy in the last 3 years.
• Blood clotting disorders (INR > 1.5, PLT < 50,000/µl - risk of bleeding during organ puncture).
• Active systemic or local infection (e.g. peritonitis, abscess).
• Severe organ failure (e.g. end-stage liver, kidney, heart failure).
• Cardiological and other diseases that threaten the use of anesthesia.
• Pancreatitis (acute or exacerbation of chronic inflammation).