Concurrent FOLFIRINOX Plus High Intensity Focused Ultrasound for Pancreatic Cancer

October 25, 2022 updated by: Jae Young Lee, Seoul National University Hospital

Therapeutic Efficacy and Safety of Concurrent FOLFIRINOX Plus HIFU for Locally Advanced/Borderline Resectable Pancreatic Cancer: A Prospective Single-center, Single-arm, Investigator-initiated, Open-labeled, Exploratory Clinical Trial

In patients diagnosed with locally advanced pancreatic cancer (LAPC)/borderline resectable pancreatic cancer (BRPC) and planned chemotherapy using FOLFIRINOX, high intensity focused ultrasound (HIFU)/FOLFIRINOX combined treatment is performed on patients who agree to this study. The combined treatment group is treated in parallel with FOLFIRINOX and HIFU for the first four cycles and then CT is taken for reaction evaluation immediately, 2 months, and 4 months after the four-cycle treatment. For the response assessment, the response rate using RECIST ver. 1.1 and operable rate are evaluated and compared with the results of already established FOLFIRINOX single treatment in the investigators' institute. Time-to-progress and overall survival are calculated.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients diagnosed with pancreatic cancer through biopsy and diagnosed with LAPC/BRPC through computed tomography (CT) or magnetic resonance imaging (MRI) are referred to this clinical trial. When the referred patients are voluntarily signed a written consent form after hearing sufficient explanations related to this study, the referred patients will be registered for this clinical trial if all criteria for selection/exception are met.

A management log will be prepared for all subjects who have signed a clinical trial agreement and are registered in the study. These management logs are used to assign sequential subject numbers to subjects registered in clinical trials, and subject numbers are assigned 'screening numbers' and 'registration numbers'.

The subjects will visit on the scheduled date to receive chemotherapy and HIFU combined therapy and will be treated in accordance with the following treatment procedures and protocols.

<Visit 1 to Visit 4: Combined Treatment, Cycle 1, Cycle 2, Cycle 3, Cycle 4 ± 14 Days>

The subjects will receive combined treatments with anticancer drugs (FOLFIRINOX) and HIFU (ALPIUS 900) over four cycles over eight weeks. Afterwards, CT for reaction evaluation is taken immediately after 4 cycles (i.e., 2 months after the onset of combined treatment). CT is taken at intervals of two months up to 6 months after the onset of combined treatment.

At the end of each combined treatment, the patient will be observed about adverse events including anticancer drug adverse events and skin change and can be back home or hospitalized for one to two days after collecting blood for blood tests according to doctor's opinion.

<Schedule and procedures for combined treatment>

Perform a total of four treatments every two weeks for eight weeks.

Combined treatment procedure

Subjects are hospitalized and given anti-cancer drugs for about 50 hours in accordance with the standard protocol for anti-cancer treatment. If the medication is canceled or postponed due to the condition of the subject, the HIFU procedure will be canceled or postponed.

After the start of chemotherapy, receive HIFU treatment within 48 hours (30 minutes to 1 hour) and go up to the inpatient ward to monitor for 1 to 2 hours. If adverse events caused by anticancer drugs have not been recovered within 24 hours of administration or adverse events have not been fully recovered from previous HIFU procedures, the HIFU procedure may be canceled or postponed under the judgment of the investigator.

When combined treatment (anti-cancer drug administration) is completed, the subject shall be hospitalized for one to two days or return home depending on the physical condition of the subject.

<Treatment protocol>

Anti-cancer drug administration (FOLFIRINOX one time regimen) Oxaliplatin 85 mg/m2 (Intravenous, IV) Irinotecan 180 mg/m2 (Intravenous, IV) Leucovorin(Folic acid) 400 mg/m2 (Intravenous, IV) 5-fluorouracil 400 mg/m2 (IV push) 5-fluorouracil 2400 mg/m2 (Intravenous, IV) It is administered at the following schedule every two weeks. Day 1 : Oxaliplatin, Irinotecan, Leucovorin, 5-FU (IV-push), 5-FU (IV infusion) Day 2-3 : 5-FU (IV infusion)

The administration of anticancer drugs (FOLFIRINOX therapy) is applied equally to each treatment group and according to the institution's standard procedure. The FOLFIRINOX dose and administration cycle (interval) can be adjusted by the researcher's judgment depending on the condition and progress of the subject. Anti-cancer drugs used in clinical trials are licensed medicines and are used within the scope of permission.

<HIFU treatment (one-time treatment)>

The HIFU procedure is in accordance with the HIFU parameter, and the details of the pre-procedure, procedure, and post-procedure care of the subjects are in accordance with the manufacturer's ALPIUS 900 User Manual.

HIFU parameter

Acoustic Intensity 2.0 kilowatt (kW)/cm2, Duty cycle 1%, Exposure time 3 sec/point, Pulse repetition frequency (PRF) 10 Hz

Immediately, 2 months, and 4 months after completion of the 4th cycle combined treatment, the subjects visit the hospital to conduct the efficacy and safety assessment. The dose-limiting toxicity (DLT) or adverse device effect (ADE) assessment will be evaluated on each planned visit.

Treatment after the end of combined treatment of HIFU/Anticancer drug Subsequent treatment of patients who have completed HIFU/anti-cancer combined treatment in the first 4 cycles is determined and performed according to findings of CT performed after 4 cycles of combined treatment, overall physical condition of patients, and standard care guidelines. The implementation of surgery, continuation of FOLFIRINOX chemotherapy, conversion to other anticancer drugs, and further radiation therapy can be considered as possible treatments. This assessment is conducted after 8 and 12 cycles of treatment if the treatment continues for FOLFIRINOX chemotherapy, and further treatment policies are determined in accordance with the standard care guidelines. If surgery is performed after 8 or 12 cycles, additional cancer or radiotherapy may be performed after surgery according to surgery and pathological findings, and it is required to be determined in accordance with the standard care guidelines.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Recruiting
        • Seoul National University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jae Young Lee, MD
        • Sub-Investigator:
          • Sang-Hyup Lee, MD
        • Sub-Investigator:
          • Jin-Young Jang, MD
        • Sub-Investigator:
          • Hong Beom Kim, MD
        • Sub-Investigator:
          • Dong Ho Lee, MD
        • Sub-Investigator:
          • In Rae Cho, MD
        • Sub-Investigator:
          • Hang-Rae Kim, phD
        • Sub-Investigator:
          • Soo Yeon Kang, CRC
        • Sub-Investigator:
          • Dong Hyuk Park, Technician
        • Sub-Investigator:
          • Seong Ho Choi, CRC
        • Sub-Investigator:
          • Hyun Ji Lee, CRC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

All of the following selection criteria must be met before participants can be registered for this clinical trial.

  1. Adults over 19-85
  2. Persons with a Karnofsky Performance Scale (KPS) of 70 percent or more;
  3. A person diagnosed as a tubular adenocarcinoma through biopsy.
  4. A person diagnosed with LAPC/BRPC by computed tomography (CT) or magnetic resonance imaging (MRI)
  5. A person willing to voluntarily agree to a clinical trial and comply with the test plan

Exclusion Criteria:

The following exclusion criteria may not be registered in clinical trials.

  1. The presence of a cystic lesion within pancreatic cancer to be treated with HIFU or at the pancreas adjacent to the pancreatic cancer.
  2. The presence of a wide range of scar or surgical clips observed in the passage through the ultrasonic beam.
  3. In case proper ultrasound images for HIFU procedures are not shown
  4. A person who cannot lie down in a comfortable position.
  5. A person who has difficulty communicating
  6. A person who has experience in toxic or hypersensitive reactions to FOLFIRINOX anticancer drugs.
  7. A person pregnant or breastfeeding
  8. Pancreatic cancer patients who have previously been anti-cancer treatment
  9. If severe side effects such as aortic rupture, duodenum perforation, gastrointestinal damage or intestinal necrosis are expected due to HIFU procedures.
  10. Other cases where participation in this clinical trial is judged inappropriate by the investigator (specific reasons should be recorded in the case report form)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CureHIFUPanc
Patients diagnosed with locally advanced/borderline resectable pancreatic cancer through biopsy and CT/MRI imaging and planned to undergo anti-cancer treatment using FOLFIRINOX
Device: ALPIUS 900, an ultrasound-guided high intensity focused ultrasound system
Device to deliver mechanical stress and force to enhance drug delivery, using focused ultrasound
Drug: FOLFIRINOX regimen

a chemotherapy regimen for treatment of advanced pancreatic cancer

  • FOL : folinic acid (leucovorin), a vitamin B derivative that enhances the effects of 5-FU
  • F : 5-FU, a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops DNA synthesis
  • IRIN : irinotecan (eloxatin), a platinum-based antineoplastic agent, which inhibits DNA repair and/or DNA synthesis.
  • OX - oxaliplatin (Eloxatin), a platinum-based antineoplastic agent, which inhibits DNA repair and/or DNA synthesis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
2-month Tumor Response
Time Frame: immediately after the completion of the four-cycle combined treatment (each cycle is 14 days)
Based on CT findings taken immediately after completion of the four-cycle combined treatment (each cycle is 14 days), 2-month tumor response is evaluated with complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to the Response Evaluation Criteria In Solid Tumors (RECIST, Ver 1.1)
immediately after the completion of the four-cycle combined treatment (each cycle is 14 days)
4-month Tumor Response
Time Frame: 4 months after the start of combined treatment
Based on CT findings taken obtained 4 months after the start of combined treatment, 4-month tumor response is evaluated with complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to the Response Evaluation Criteria In Solid Tumors (RECIST, Ver 1.1)
4 months after the start of combined treatment
6-month Tumor Response
Time Frame: 6 months after the start of combined treatment
Based on CT findings taken obtained 6 months after the start of combined treatment, 6-month tumor response is evaluated with complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to the Response Evaluation Criteria In Solid Tumors (RECIST, Ver 1.1)
6 months after the start of combined treatment
Percentage of subjects that were subject to surgical resection
Time Frame: 4 months or 6 months after the start of the combined treatment
When surgery is determined according to American Joint Committee on Cancer (AJCC), 8 edition guidelines based on computed tomography (CT) images taken 4 months or 6 months after the start of the combined treatment, the percentage of subjects who were able to be operated on compared to the total number of registered subjects is calculated.
4 months or 6 months after the start of the combined treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time-to-Progression
Time Frame: from the date of diagnosis of pancreatic cancer or from the start date of combined treatment of pancreatic cancer until the date of first documented progression, assessed up to 24 month
The time taken from the date of diagnosis of pancreatic cancer or from the start date of combined treatment of pancreatic cancer until the date of first documented progression, assessed up to 24 months. Judging by RECIST ver. 1.1
from the date of diagnosis of pancreatic cancer or from the start date of combined treatment of pancreatic cancer until the date of first documented progression, assessed up to 24 month
Survival time
Time Frame: from the date of diagnosis of pancreatic cancer or the start date of combined treatment of pancreatic cancer until the date of death from any cause, assessed up to 24 months
The time taken from the date of diagnosis of pancreatic cancer or the start date of combined treatment of pancreatic cancer until the date of death from any cause
from the date of diagnosis of pancreatic cancer or the start date of combined treatment of pancreatic cancer until the date of death from any cause, assessed up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Collaborators

Focused Ultrasound Foundation
Synex Consulting Ltd

Investigators

  • Principal Investigator: Jae Young Lee, MD, Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 9, 2021

Primary Completion (Anticipated)

March 1, 2023

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

October 2, 2021

First Submitted That Met QC Criteria

February 20, 2022

First Posted (Actual)

March 2, 2022

Study Record Updates

Last Update Posted (Actual)

October 26, 2022

Last Update Submitted That Met QC Criteria

October 25, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006-154-1135

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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