Clinical trial NCT06211933: Evaluation of the High Intensity Focused Ultrasound (HIFU) Technique for Patients With Unresectable Pancreatic Tumor Treatment (PULS)
Official title: Phase I/II Study Evaluating the Safety and Efficacy of the HIFU Technique in Patients With Unresectable Pancreatic Tumor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Resectable Pancreas Carcinoma
Keywords: Oncology
Phase I
Phase II
Phase I/II
HIFU
High Intensity Focalised Ultrasounds
Efficacy
Safety
Medical Device
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2024-01-18
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: HIFU intervention at day 0 for each patient included.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Tolerance profile of HIFU intervention
timeFrame: Up to 30 days after HIFU intervention
measure: Survival rate at 12 months after HIFU intervention
timeFrame: Up to 12 months after HIFU intervention
Secondary outcomes:
measure: Tumor ablation rate by HIFU
timeFrame: Up to 28 days after inclusion
measure: Intra-operative and post-operative complications linked to the HIFU intervention
timeFrame: Up to 3 months after HIFU intervention
measure: Feasibility of HIFU intervention
timeFrame: Up to 28 days after inclusion
measure: Progression-Free Survival (PFS)
timeFrame: From date of inclusion until the date of first documented progression or date of death from any cause, whichever came first or until the date of the last update for patients without progression, assessed up to 60 months after inclusion
measure: Local Progression-Free Survival (local PFS)
timeFrame: From date of inclusion to the date of first disease progression or death or last update, assessed up to 60 months
measure: Overall Survival (OS)
timeFrame: From date of inclusion to the date of death or date of last update, assessed up to 60 months
measure: Length of hospitalization
timeFrame: From date of HIFU intervention to the date of discharge from hospitalization, assessed up to 3 months
measure: Rehospitalization rate during the first 30 days after HIFU intervention.
timeFrame: From the date of HIFU intervention to 30 days after HIFU intervention
measure: Rate of secondary resectability
timeFrame: From date of HIFU intervention to the date of last patient's last visit, assessed up to 60 months
measure: Incidence and severity of adverse events
timeFrame: From the date of intervention to the date of last patient's last visit, assessed up to 60 months.
measure: Quality of Life (QoL)
timeFrame: From the date of inclusion to 6 months after HIFU intervention
measure: Clinical benefice rate regarding pain
timeFrame: From the date of inclusion to the date of last patient's last visit, assessed up to 60 months.
measure: Clinical benefice rate regarding weight
timeFrame: From the date of inclusion to the date of last patient's last visit, assessed up to 60 months.
measure: Clinical benefice rate regarding performance status
timeFrame: From the date of inclusion to the date of last patient's last visit, assessed up to 60 months.
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Estaing
state: Auvergne Rhone-Alpes
city: Lyon
country: France
facility: Centre Léon Bérard
state: Rhone-alpes
Study officials:
References: