Evaluation of the High Intensity Focused Ultrasound (HIFU) Technique for Patients With Unresectable Pancreatic Tumor Treatment (PULS)

Phase I/II Study Evaluating the Safety and Efficacy of the HIFU Technique in Patients With Unresectable Pancreatic Tumor

This is a phase I/II, multicenter trial for patients with locally advanced and unresectable pancreatic tumours :

• A Phase I evaluating the tolerance of intraoperative High Intensity Focused Ultrasound (HIFU) intervention on the pancreatic lesion.
• A non-randomized Phase II evaluating the preliminary efficacy of the HIFU intervention on the pancreatic lesion.

Patients included in Phase I will be monitored and included in the Phase II evaluation.

The PULS study is designed for patients with a locally advanced tumour of the pancreas (known as pancreatic adenocarcinoma) that has previously been treated with several cycles of chemotherapy and cannot be removed by surgery.

Pancreatic adenocarcinomas are often diagnosed at an advanced stage and only 15% to 20% of patients are candidates for surgery to remove the tumour. In the remaining cases, around a third of patients have metastatic disease at the time of diagnosis. The remaining third have locally advanced pancreatic cancer. In these cases, chemotherapy with or without radiotherapy is the standard treatment. The low proportion of patients who can benefit from surgery and the poor response to chemotherapy make the development of new treatments vital and urgent.

For locally advanced cancers, we want to develop and evaluate a new form of treatment based on a medical device using high intensity focused ultrasound (HIFU), after chemotherapy.

HIFU is a recent technology that uses therapeutic ultrasound. All HIFU procedures currently performed are carried out using an extracorporeal approach.

The aim of this research is therefore to assess the safety and efficacy of HIFU ablation of locally advanced pancreatic tumours.

This trial is a two stages (phase I and II) open label non comparative study. The first step of this study is to evaluate the safety of the HIFU intervention on 3 to 6 patients included. Patients will be included one by one, with a safety committee after each intervention. The total number of patients included in phase I will depend on the complications rate : If no serious complications are observed among the first 3 patients treated, the phase II study can begin. If a serious complication is observed, 3 additional patients will be included in phase I. The transition to phase II will be effective if a maximum of 1 complication out of the 6 patients included is observed. In the other cases, if at least 2 serious complications are observed for 3 to 6 patients included, the study will be definitively stopped.

The second step of this study is to evaluate the efficacy of the HIFU intervention on 26 patients including the patients of phase I.

Each patient will be follow for two years after the HIFU intervention. Un update of vital status will be made annually until the last patient's last visit.

Sample size was thus evaluated by analogy with an A'Hern's. If at least 14 successes are observed among 26 patients, HIFU treatment will be considered of interest.

Inclusion Criteria:

• Age ≥ 18 years at the day of consenting to the study
• Patient with histologically confirmed locally advanced (unresectable) pancreatic adenocarcinoma according to the National Comprehensive Cancer Network (NCCN) 2020 classification
• Unifocal pancreatic lesion with a maximum diameter of 4 cm
• Non-progressive disease after 4 months of first-line chemotherapy or after 2 months of chemotherapy in case of limiting toxicity contraindicating continuation of chemotherapy;
• Preoperative imaging including CT-scan, MRI of the liver and Positron Emission Computed Tomography scan (PET-CT scan) (except for absolute medical contraindications), within 4 weeks prior to HIFU treatment
• Eastern Cooperative Oncology Group performance status ≤ 2
• Adequate hematologic parameters defined by platelets ≥ 100 Giga/l and hemoglobin ≥ 8 g/dl
• Ability to understand and willingness for follow-up visits
• Patient affiliated to a health insurance scheme (or beneficiary of such a scheme)
• Signed and dated informed consent document indicating that the patient has been informed of all aspects of the trial prior to enrolment

Exclusion Criteria:

• Local recurrence of previously operated pancreatic cancer
• Metastatic pancreatic carcinoma
• History of major pancreatic resection
• Chemotherapy completed less than 2 weeks ago
• History of radiotherapy to the pancreas
• Pregnant women
• Possibility of R0 resection with venous reconstruction
• Inability to undergo study follow-up for geographical, social or psychological reasons
• Patient requiring tutorship or curatorship or patient deprived of liberty
• Patient under psychiatric care against his wishes