Adjuvant PIPAC in Gastric Cancer Patients

NCT04047004 | Completed Phase 1 DMC

• 1 other identifier: PIPAC-OPC4
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 2

Brief Summary

In this study patients will be offered intraperitoneal atomized chemotherapy as a supplement to the standard treatment of high-risk gastric cancer (laparoscopic removal of the stomach). Two commercially available oncologic drugs will be used (doxorubicin and cisplatin).

Conditions

Gastric Adenocarcinoma; Gastric Cancer

Keywords

Gastric adenocarcinoma; Intraperitoneal chemotherapy; Laparoscopic gastrectomy; Gastric cancer; Surgery

Outcome Measures

Primary Outcomes (2)

• Medical adverse events

  According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.

  30 days

• Surgical complications

  According to the Dindo-Clavien classification

  30 days

Secondary Outcomes (3)

• Length of stay

  30 days

• Positive peritoneal lavage

  30 days

• Adjuvant chemotherapy

  30 days

Study Arms (1)

High-risk gastric cancer patients

EXPERIMENTAL

The study population of high-risk gastric cancer patients will be offered one session of PIPAC immediately after laparoscopic removal of the stomach.

Drug: Doxorubicin; Drug: Cisplatin

Interventions

Doxorubicin DRUG

Conventional PIPAC with doxorubicin (2.1 mg/m2 body surface in 50ml saline) is performed through the CE-certified nebulizer by certified PIPAC surgeons directly after the completion of the laparoscopic gastric resection and reconstruction using the remaining relevant ports. Chemotherapy is installed at a rate of 0.5-0.8 ml/s with a maximum pressure of 300 pressure per square inch and 30 minutes of simple diffusion.

High-risk gastric cancer patients

Cisplatin DRUG

Conventional PIPAC with cisplatin (10.5 mg/m2 body surface in 150ml saline) is performed through the CE-certified nebulizer by certified PIPAC surgeons directly after the completion of the laparoscopic gastric resection and reconstruction using the remaining relevant ports. Chemotherapy is installed at a rate of 0.5-0.8 ml/s with a maximum pressure of 300 pressure per square inch and 30 minutes of simple diffusion.

High-risk gastric cancer patients

Eligibility Criteria

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

You may qualify if:

• Patients with high-risk GAC defined as: Diffuse cancer (signet ring cells predominant) or clinical stage: cTany + cN2-3 or cT3-T4 + cNany or GAC patients with preoperative positive peritoneal cytology submitted to laparoscopic gastrectomy (+/- neoadjuvant treatment).
• Age 18 or above
• Written informed consent

You may not qualify if:

• Previous allergic reaction to cisplatin, doxorubicin or other platinum containing compounds.
• Renal impairment, defined as GFR \< 40 ml/min (Cockcroft-Gault Equation).
• Myocardial insufficiency, defined as NYHA class 3-4.
• Impaired liver function defined as bilirubin ≥ 1.5 x UNL (upper normal limit).
• Inadequate haematological function defined as absolute neutrophil count (ANC) ≤ 1.5 x 10\^9/l and platelets ≤ 100 x 10\^9/l.
• Any other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.

Sponsors & Collaborators

• Michael Bau Mortensen: lead

Study Sites (2)

Odense PIPAC Center, Department of Surgery, Odense University Hospital

Odense, 5000, Denmark

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Related Publications (17)

• Yang D, Hendifar A, Lenz C, Togawa K, Lenz F, Lurje G, Pohl A, Winder T, Ning Y, Groshen S, Lenz HJ. Survival of metastatic gastric cancer: Significance of age, sex and race/ethnicity. J Gastrointest Oncol. 2011 Jun;2(2):77-84. doi: 10.3978/j.issn.2078-6891.2010.025.

  PMID: 22811834 BACKGROUND

• Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai BC, Ho J, Unverzagt S. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017 Aug 29;8(8):CD004064. doi: 10.1002/14651858.CD004064.pub4.

  PMID: 28850174 BACKGROUND

• Al-Batran SE, Homann N, Pauligk C, Illerhaus G, Martens UM, Stoehlmacher J, Schmalenberg H, Luley KB, Prasnikar N, Egger M, Probst S, Messmann H, Moehler M, Fischbach W, Hartmann JT, Mayer F, Hoffkes HG, Koenigsmann M, Arnold D, Kraus TW, Grimm K, Berkhoff S, Post S, Jager E, Bechstein W, Ronellenfitsch U, Monig S, Hofheinz RD. Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial. JAMA Oncol. 2017 Sep 1;3(9):1237-1244. doi: 10.1001/jamaoncol.2017.0515.

  PMID: 28448662 BACKGROUND

• Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Konigsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jager E, Monig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. doi: 10.1016/S1470-2045(16)30531-9. Epub 2016 Oct 22.

  PMID: 27776843 BACKGROUND

• Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531.

  PMID: 16822992 BACKGROUND

• Bringeland EA, Wasmuth HH, Gronbech JE. Perioperative chemotherapy for resectable gastric cancer - what is the evidence? Scand J Gastroenterol. 2017 Jun-Jul;52(6-7):647-653. doi: 10.1080/00365521.2017.1293727. Epub 2017 Feb 28.

  PMID: 28276825 BACKGROUND

• Takebayashi K, Murata S, Yamamoto H, Ishida M, Yamaguchi T, Kojima M, Shimizu T, Shiomi H, Sonoda H, Naka S, Mekata E, Okabe H, Tani T. Surgery-induced peritoneal cancer cells in patients who have undergone curative gastrectomy for gastric cancer. Ann Surg Oncol. 2014 Jun;21(6):1991-7. doi: 10.1245/s10434-014-3525-9. Epub 2014 Feb 6.

  PMID: 24499832 BACKGROUND

• De Andrade JP, Mezhir JJ. The critical role of peritoneal cytology in the staging of gastric cancer: an evidence-based review. J Surg Oncol. 2014 Sep;110(3):291-7. doi: 10.1002/jso.23632. Epub 2014 May 22.

  PMID: 24850538 BACKGROUND

• Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006 Aug;6(8):583-92. doi: 10.1038/nrc1893.

  PMID: 16862189 BACKGROUND

• Bentrem D, Wilton A, Mazumdar M, Brennan M, Coit D. The value of peritoneal cytology as a preoperative predictor in patients with gastric carcinoma undergoing a curative resection. Ann Surg Oncol. 2005 May;12(5):347-53. doi: 10.1245/ASO.2005.03.065. Epub 2005 Mar 31.

  PMID: 15915368 BACKGROUND

• Ji ZH, Peng KW, Li Y. Intraperitoneal free cancer cells in gastric cancer: pathology of peritoneal carcinomatosis and rationale for intraperitoneal chemotherapy/hyperthermic intraperitoneal chemotherapy in gastric cancer. Transl Gastroenterol Hepatol. 2016 Sep 19;1:69. doi: 10.21037/tgh.2016.08.03. eCollection 2016.

  PMID: 28138635 BACKGROUND

• Coccolini F, Catena F, Glehen O, Yonemura Y, Sugarbaker PH, Piso P, Ceresoli M, Montori G, Ansaloni L. Effect of intraperitoneal chemotherapy and peritoneal lavage in positive peritoneal cytology in gastric cancer. Systematic review and meta-analysis. Eur J Surg Oncol. 2016 Sep;42(9):1261-7. doi: 10.1016/j.ejso.2016.03.035. Epub 2016 Apr 19.

  PMID: 27134147 BACKGROUND

• Grass F, Vuagniaux A, Teixeira-Farinha H, Lehmann K, Demartines N, Hubner M. Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. Br J Surg. 2017 May;104(6):669-678. doi: 10.1002/bjs.10521.

  PMID: 28407227 BACKGROUND

• Graversen M, Lundell L, Fristrup C, Pfeiffer P, Mortensen MB. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) as an outpatient procedure. Pleura Peritoneum. 2018 Nov 27;3(4):20180128. doi: 10.1515/pp-2018-0128. eCollection 2018 Dec 1.

  PMID: 30911669 BACKGROUND

• Graversen M, Detlefsen S, Bjerregaard JK, Fristrup CW, Pfeiffer P, Mortensen MB. Prospective, single-center implementation and response evaluation of pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal metastasis. Ther Adv Med Oncol. 2018 Jun 1;10:1758835918777036. doi: 10.1177/1758835918777036. eCollection 2018.

  PMID: 29899763 BACKGROUND

• Graversen M, Pedersen PB, Mortensen MB. Environmental safety during the administration of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Pleura Peritoneum. 2016 Dec 1;1(4):203-208. doi: 10.1515/pp-2016-0019. Epub 2016 Nov 25.

  PMID: 30911624 BACKGROUND

• Graversen M, Fristrup C, Kristensen TK, Larsen TR, Pfeiffer P, Mortensen MB, Detlefsen S. Detection of free intraperitoneal tumour cells in peritoneal lavage fluid from patients with peritoneal metastasis before and after treatment with pressurised intraperitoneal aerosol chemotherapy (PIPAC). J Clin Pathol. 2019 May;72(5):368-372. doi: 10.1136/jclinpath-2018-205683. Epub 2019 Feb 12.

  PMID: 30755498 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Doxorubicin; Cisplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Signe Bremholm Ellebæk, MD, PhD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Consultant, DMSci, PhD, MD

Model Details: Prospective, multicenter, non-randomized, non-blinded, open-label

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: August 6, 2019
• Study Start: March 11, 2020
• Primary Completion: June 30, 2022
• Study Completion: October 1, 2022
• Last Updated: October 6, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); DK (1)