Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Hematinics

All Drugs and Chemicals

Liver Extracts

The shootings will concern the healthy liver to remove, distant to the important vascular structures and metastases. Two HIFU shootings will be made on each patient:

* One hurt on the surface starting from the Glisson capsule and extending to subjacent hepatic parenchyma.
* One hurt at given depth, at least 10 mm deeper than the hurt done on the surface NB: The shooting depth will determined for each patient at the beginning of the operation, considering preoperative exams (scans, etc.), size and location of the liver part to be resected and physical structure of the patient.

HIFU

The shootings will concern healthy liver to be resected, distant (step 1) then close (step 2) to the important vascular structures of the liver. Several shootings HIFU will be made on each patient (ideally 4 hurts, minimum 2 hurts)

Shootings will concern small metastases (≤ 20 mm) and peri lesional healthy liver. They will be juxtaposed on multiple plans in order to generate a large hurt containing the metastasis targeted and guaranteeing a sufficient safety margin in healthy liver.

Several metastases can be treated in the same patient

Séverine METZGER

Michel RIVOIRE

The purpose of this study is to assess the feasibility, safety and efficacy of High Intensity Focused Ultrasound (HIFU) patients undergoing hepatectomy for colorectal liver metastases. This is a phase I/II study.

Justification and interest of the study:

Colorectal liver metastases (CLM) are a major public health issue (16 000 deaths each year in France). To date, complete resection of CLM offers the only potential curative approach. However, only a minority of patients (10 to 20%) is candidates. 5-year survival rates after liver resection are ranged from 20 to 35%. Consequently, alternative locally targeted therapies (radiofrequency, cryotherapy, laser, microwave) have been developed and evaluated. Their use presents many limitations: invasive procedures requiring the intraparenchymal introduction of a probe, impossibility of an accurate monitoring in real-time, small size destruction, time-consuming, high recurrence rate. The development of a non-invasive and more accurate technique combined to surgery is required.

High Intensity Focused Ultrasound (HIFU) is a new approach, which enables to generate irreversible cell death through coagulative necrosis in a few seconds. There's no cooling effect of the perfusion because of the shortness of the phenomenon.

The surgical team of the Centre Leon Berard, in collaboration with the INSERM U556 one, has undertaken a research program on CLM treatment by HIFU. A new and very powerful device, without the previously named limitations, has been developed. Preclinical studies have revealed the interest, the feasibility and the safety of this process. These results enable considering preceding the program with an early clinical study.

Experimental design:

Prospective, monocentric phase I/II study evaluating a surgical medical device (SMD).

HIFU SMD will be evaluated in clinical conditions, in patients undergoing hepatectomy for colorectal liver metastases. Several HIFU "shootings" (the number will be function of the advancement of the study) will be performed on the liver witch will be resected

Objectives and main assessment criteria:

1. st part: Phase I - on the healthy liver to remove. Feasibility 1, Safety 2, Tolerance 3. Success = 1 Ability to perform shootings, supplementary duration of intervention \< 30 minutes; 2 Asepsis, absence of lesion of nearly tissues; 3 Preservation of hemodynamic and respiratory constants.
2. nd part: Phase IIa - on the healthy liver to remove, distant then close to the vascular structures of the liver.

   Ability of targeting shootings. Success = distance from the epicentre of the HIFU lesion to the mark previously positioned in the liver ≤ 5mm.
3. rd part: Phase IIb - on metastases to remove. Ability, by summation of HIFU lesions, to generate " macro-lesions " including a metastasis and insuring a sufficient safety margin in the healthy tissue.

Success = macro-lesion generated in negative margins.

Number of patients:

1. st part: The inclusion from 2 to 6 patients is required. The next step (phase II) will depend on:

   * 1st analysis after 2 patients:

     * If \< 2 failures: continuation,
     * If 2 failures: cessation of the study.
   * 2nd analysis after 6 patients:

     * If \< 3 failures: continuation (phase II),
     * If ≥ 3 failures: cessation.
2. nd part: Three patients will be successively included in each of the 2 landings (appendix 1):

   * If no failure: continuation (2nd landing / Phase IIb),
   * If ≤ 2 failures: + 3 patients,
   * If \> 2 failures on 6 patients: cessation,
   * If ≤ 2 failures on 6 patients: continuation (2nd landing / phase IIb),
   * If 3 failures: cessation.
3. rd part:

   * p0 = 0.70 = upper limit of the success rate resulting in the inefficacy of HIFU multi-shootings.
   * p1 = 0.90 = lower limit of the success rate resulting in the efficacy of HIFU shootings.

With a 5% risk of type I error and a 80% power, 28 metastases have to be targeted by HIFU in order to conclude in one-sided situation. Taking into account that an average of 1.5 metastases will be targeted in each patient, 20 patients will be enrolled. 24 observed successes will allow concluding in the reject of H0 to accept H1.

Study to Evaluate a High Intensity Focused Ultrasound (HIFU) Procedure in Patient With Liver Metastases

A Phase I-II Study to Evaluate, in Patients Operated for a Hepatic Resection of Colorectal Liver Metastases, a High Intensity Focused Ultrasound (HIFU) Procedure: Feasibility, Safety and Accuracy.

both the distance between the hurt epicentre generated by hifu and a mark. These sizes will be measured in mm during anatomopathological exam.

between the hurt limit and a vessel border previously marked. These sizes will be measured in mm during anatomopathological exam.

The aim is to be free to generate a HIFU hurt in at least 80 % of the total liver volume

Precise measure given in mm by the anatomopathologist

no evidence of hurt on peripheral tissues (Glisson capsule on the opposite side of the HIFU shootings entrance area, retro-peritoneal, retro-hepatic tissues and diaphragm

hemodynamic, respiratory, body temperature

hurt dimensions comparison (diameters, depth, volume, etc. - in mm), blind-measured, with echography in a first time and in a second time, right after the resection, in anatomopathology

National Cancer Institute, France

Cancéropôle Lyon Auvergne Rhône-Alpes

Centre Leon Berard

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Adenocarcinoma

Carcinoma, Pancreatic Ductal

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Carcinoma, Ductal

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

Folfirinox

1,0 ml SonoVue 8ul/ml dispersion is given 9 times at 3,5 minute intervals 9 times, a total dosage of 9 ml. The experimental treatment lasts for 31,5 minutes every treatment day. Administered by authorized site personnel only

SonoVue

FOLFIRINOX Regime according to Norwegian national guidelines

Chemotherapy

Eva Hofsli, md phd

Patients with inoperable pancreatic cancer have extremely poor prognosis with five year survival below 8% in Norway. Life-prolonging chemotherapy has very limited effect, but is the only therapeutic option for these patients. This tumor is characterized by poor uptake and chemoresistance. Toxic effects on healthy tissue restrict doses applied and maintenance of treatment intensity. This severely limits clinical outcome. Increasing the local uptake of chemotherapy has potential benefits for patients in connection to side effects, survival and possible cure. Treatment with Focused Ultrasound (FUS) combined with microbubbles (MBs) is proved promising to improve treatment response in animal and clinical trials. Ultrasound can induce biological effects deep inside the body without surgical intervention. This opens for local delivery of drugs at desired sites. FUS in combination with regular contrast MBs has been reported to influence the delivery of drugs to tumors.

In this trial FUS and MB will be applied to locally advanced pancreatic cancers shortly after the administration of conventional chemotherapy. Primary aim of the trial is to investigate whether the effect of the cytostatic drug, measured in tumor volume, can be increased.

Ultrasound-enhanced Uptake of Chemotherapy in Patients With Inoperable Pancreatic Ductal Adenocarcinoma

Ultrasound-enhanced Uptake of Chemotherapy in Patients With Inoperable Pancreatic Ductal Adenocarcinoma - A Randomized Controlled Trial

Individual participant data that underlie the results reported in this article, after deidentification(text, tables, figures, and appendices). Interested researchers who provide a reasonable, sound proposal are encouraged to direct this to the first author.

measured by segmented tumor volumes on Computed Tomography of primary PDAC tumor from before treatment (baseline) to after 1 cycle of treatment

Toxicity reported by patients during structured interview after treatment. Type of side effects and severity according to Common Toxicity Criteria (CTC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study to Evaluate a High Intensity Focused Ultrasound (HIFU) Procedure in Patient With Liver Metastases	NCT01489787	Neoplasm Metast...	HIFU HIFU HIFU	18 Years -	Centre Leon Berard
Ultrasound-enhanced Uptake of Chemotherapy in Patients With Inoperable Pancreatic Ductal Adenocarcinoma	NCT04146441	Carcinoma, Panc...	SonoVue Chemotherapy	19 Years - 89 Years	St. Olavs Hospital

Spots Global Cancer Trial Database for ultrasonic therapy