Concurrent FOLFIRINOX Plus High Intensity Focused Ultrasound for Pancreatic Cancer

NCT05262452 | Unknown DMC

• 1 other identifier: 2006-154-1135
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Cancer Non-resectable; Chemotherapy Effect; Ultrasound Therapy

Keywords

High-Intensity Focused Ultrasound Therapy,; Combined Modality Therapy; Clinical Trial; Neoadjuvant Therapy; Survival Analysis; pancreatic cancer

Outcome Measures

Primary Outcomes (4)

• 2-month Tumor Response

  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

  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

  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

  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 Outcomes (2)

• Time-to-Progression

  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

  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

Study Arms (1)

CureHIFUPanc

EXPERIMENTAL

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; Drug: FOLFIRINOX regimen

Interventions

ALPIUS 900, an ultrasound-guided high intensity focused ultrasound system DEVICE

Device to deliver mechanical stress and force to enhance drug delivery, using focused ultrasound

CureHIFUPanc

FOLFIRINOX regimen DRUG

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

CureHIFUPanc

Eligibility Criteria

• Age: 19 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All of the following selection criteria must be met before participants can be registered for this clinical trial.
• Adults over 19-85
• Persons with a Karnofsky Performance Scale (KPS) of 70 percent or more;
• A person diagnosed as a tubular adenocarcinoma through biopsy.
• A person diagnosed with LAPC/BRPC by computed tomography (CT) or magnetic resonance imaging (MRI)
• A person willing to voluntarily agree to a clinical trial and comply with the test plan

You may not qualify if:

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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Focused Ultrasound Foundation: collaborator
• Synex Consulting Ltd: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Related Publications (19)

• Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.

  PMID: 21561347 BACKGROUND

• Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Chone L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O'Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB; Canadian Cancer Trials Group and the Unicancer-GI-PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018 Dec 20;379(25):2395-2406. doi: 10.1056/NEJMoa1809775.

  PMID: 30575490 BACKGROUND

• Murphy JE, Wo JY, Ryan DP, Jiang W, Yeap BY, Drapek LC, Blaszkowsky LS, Kwak EL, Allen JN, Clark JW, Faris JE, Zhu AX, Goyal L, Lillemoe KD, DeLaney TF, Fernandez-Del Castillo C, Ferrone CR, Hong TS. Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):963-969. doi: 10.1001/jamaoncol.2018.0329.

  PMID: 29800971 BACKGROUND

• Choi YH, Lee SH, You MS, Shin BS, Paik WH, Ryu JK, Kim YT, Kwon W, Jang JY, Kim SW. Prognostic Factors for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer Receiving Neoadjuvant FOLFIRINOX. Gut Liver. 2021 Mar 15;15(2):315-323. doi: 10.5009/gnl19182.

  PMID: 32235008 BACKGROUND

• Hackert T, Sachsenmaier M, Hinz U, Schneider L, Michalski CW, Springfeld C, Strobel O, Jager D, Ulrich A, Buchler MW. Locally Advanced Pancreatic Cancer: Neoadjuvant Therapy With Folfirinox Results in Resectability in 60% of the Patients. Ann Surg. 2016 Sep;264(3):457-63. doi: 10.1097/SLA.0000000000001850.

  PMID: 27355262 BACKGROUND

• Wu F, Wang ZB, Zhu H, Chen WZ, Zou JZ, Bai J, Li KQ, Jin CB, Xie FL, Su HB. Feasibility of US-guided high-intensity focused ultrasound treatment in patients with advanced pancreatic cancer: initial experience. Radiology. 2005 Sep;236(3):1034-40. doi: 10.1148/radiol.2362041105. Epub 2005 Jul 29.

  PMID: 16055692 BACKGROUND

• Vidal-Jove J, Perich E, Del Castillo MA. Ultrasound Guided High Intensity Focused Ultrasound for malignant tumors: The Spanish experience of survival advantage in stage III and IV pancreatic cancer. Ultrason Sonochem. 2015 Nov;27:703-706. doi: 10.1016/j.ultsonch.2015.05.026. Epub 2015 May 27.

  PMID: 26044461 BACKGROUND

• Marinova M, Huxold HC, Henseler J, Mucke M, Conrad R, Rolke R, Ahmadzadehfar H, Rauch M, Fimmers R, Luechters G, Cuhls H, Radbruch L, Schild HH, Strunk H. Clinical Effectiveness and Potential Survival Benefit of US-Guided High-Intensity Focused Ultrasound Therapy in Patients with Advanced-Stage Pancreatic Cancer. Ultraschall Med. 2019 Oct;40(5):625-637. doi: 10.1055/a-0591-3386. Epub 2018 Apr 17.

  PMID: 29665583 BACKGROUND

• Li T, Wang YN, Khokhlova TD, D'Andrea S, Starr F, Chen H, McCune JS, Risler LJ, Mashadi-Hossein A, Hingorani SR, Chang A, Hwang JH. Pulsed High-Intensity Focused Ultrasound Enhances Delivery of Doxorubicin in a Preclinical Model of Pancreatic Cancer. Cancer Res. 2015 Sep 15;75(18):3738-46. doi: 10.1158/0008-5472.CAN-15-0296. Epub 2015 Jul 27.

  PMID: 26216548 BACKGROUND

• Lee ES, Lee JY, Kim H, Choi Y, Park J, Han JK, Choi BI. Pulsed high-intensity focused ultrasound enhances apoptosis of pancreatic cancer xenograft with gemcitabine. Ultrasound Med Biol. 2013 Nov;39(11):1991-2000. doi: 10.1016/j.ultrasmedbio.2013.06.004. Epub 2013 Aug 22.

  PMID: 23972483 BACKGROUND

• Lee JY, Choi BI, Ryu JK, Kim YT, Hwang JH, Kim SH, Han JK. Concurrent chemotherapy and pulsed high-intensity focused ultrasound therapy for the treatment of unresectable pancreatic cancer: initial experiences. Korean J Radiol. 2011 Mar-Apr;12(2):176-86. doi: 10.3348/kjr.2011.12.2.176. Epub 2011 Mar 3.

  PMID: 21430934 BACKGROUND

• Rapoport N, Payne A, Dillon C, Shea J, Scaife C, Gupta R. Focused ultrasound-mediated drug delivery to pancreatic cancer in a mouse model. J Ther Ultrasound. 2013 Jul 1;1:11. doi: 10.1186/2050-5736-1-11. eCollection 2013.

  PMID: 25516800 BACKGROUND

• Park EJ, Ahn YD, Lee JY. In vivo study of enhanced chemotherapy combined with ultrasound image-guided focused ultrasound (USgFUS) treatment for pancreatic cancer in a xenograft mouse model. Eur Radiol. 2018 Sep;28(9):3710-3718. doi: 10.1007/s00330-018-5355-9. Epub 2018 Mar 29.

  PMID: 29600477 BACKGROUND

• Yu MH, Lee JY, Kim HR, Kim BR, Park EJ, Kim HS, Han JK, Choi BI. Therapeutic Effects of Microbubbles Added to Combined High-Intensity Focused Ultrasound and Chemotherapy in a Pancreatic Cancer Xenograft Model. Korean J Radiol. 2016 Sep-Oct;17(5):779-88. doi: 10.3348/kjr.2016.17.5.779. Epub 2016 Aug 23.

  PMID: 27587968 BACKGROUND

• Kim JH, Kim H, Kim YJ, Lee JY, Han JK, Choi BI. Dynamic contrast-enhanced ultrasonographic (DCE-US) assessment of the early response after combined gemcitabine and HIFU with low-power treatment for the mouse xenograft model of human pancreatic cancer. Eur Radiol. 2014 Sep;24(9):2059-68. doi: 10.1007/s00330-014-3260-4. Epub 2014 Jun 25.

  PMID: 24962825 BACKGROUND

• Yoo C, Lee SS, Song KB, Jeong JH, Hyung J, Park DH, Song TJ, Seo DW, Lee SK, Kim MH, Lee SS, Kim JH, Jin HS, Park JH, Hwang DW, Lee JH, Lee W, Chang HM, Kim KP, Ryoo BY, Kim SC. Neoadjuvant modified FOLFIRINOX followed by postoperative gemcitabine in borderline resectable pancreatic adenocarcinoma: a Phase 2 study for clinical and biomarker analysis. Br J Cancer. 2020 Aug;123(3):362-368. doi: 10.1038/s41416-020-0867-x. Epub 2020 May 20.

  PMID: 32433600 BACKGROUND

• Janssen QP, Buettner S, Suker M, Beumer BR, Addeo P, Bachellier P, Bahary N, Bekaii-Saab T, Bali MA, Besselink MG, Boone BA, Chau I, Clarke S, Dillhoff M, El-Rayes BF, Frakes JM, Grose D, Hosein PJ, Jamieson NB, Javed AA, Khan K, Kim KP, Kim SC, Kim SS, Ko AH, Lacy J, Margonis GA, McCarter MD, McKay CJ, Mellon EA, Moorcraft SY, Okada KI, Paniccia A, Parikh PJ, Peters NA, Rabl H, Samra J, Tinchon C, van Tienhoven G, van Veldhuisen E, Wang-Gillam A, Weiss MJ, Wilmink JW, Yamaue H, Homs MYV, van Eijck CHJ, Katz MHG, Groot Koerkamp B. Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. J Natl Cancer Inst. 2019 Aug 1;111(8):782-794. doi: 10.1093/jnci/djz073.

  PMID: 31086963 BACKGROUND

• Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Koerkamp BG. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016 Jun;17(6):801-810. doi: 10.1016/S1470-2045(16)00172-8. Epub 2016 May 6.

  PMID: 27160474 BACKGROUND

• Rombouts SJ, Walma MS, Vogel JA, van Rijssen LB, Wilmink JW, Mohammad NH, van Santvoort HC, Molenaar IQ, Besselink MG. Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer. Ann Surg Oncol. 2016 Dec;23(13):4352-4360. doi: 10.1245/s10434-016-5373-2. Epub 2016 Jul 1.

  PMID: 27370653 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Jae Young Lee, MD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soo Yeon Kang, CRC

CONTACT

82-2-2072-3073; jumper6805@gmail.com

Jae Young Lee, MD

CONTACT

82-2-2072-3073; leejy4u@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: Patients diagnosed with locally advanced/borderline resectable pancreatic cancer through biopsy and CT/MRI imaging and planned to undergo anti-cancer treatment using FOLFIRINOX

Study Record Dates

• First Submitted: October 2, 2021
• First Posted: March 2, 2022
• Study Start: August 9, 2021
• Primary Completion: March 1, 2023
• Study Completion: December 1, 2024
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)