PIPAC for Peritoneal Metastases of Colorectal Cancer

This is multicentre, open-label, single-arm phase II study that investigates the feasibility, safety, tolerability, preliminary efficacy, costs, and pharmacokinetics or repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC-OX) as a palliative monotherapy for patients with isolated unresectable colorectal peritoneal metastases.

Sex

All

Eligible patients are adults who have:

* a World Health Organisation (WHO) performance status of ≤1;
* histological or cytological proof of PM of a colorectal or appendiceal carcinoma;
* unresectable disease determined by abdominal computed tomography (CT) and a diagnostic laparoscopy or laparotomy;
* adequate organ functions (haemoglobin ≥5.0 mmol/L, neutrophils ≥1.5 x 109/L, platelets ≥100 x 109/L, serum creatinine \<1.5 x ULN, creatinine clearance ≥30 ml/min, and liver transaminases \<5 x ULN);
* no symptoms of gastrointestinal obstruction;
* no radiological evidence of systemic metastases;
* no contraindications for oxaliplatin or 5-fluorouracil/leucovorin;
* no contraindications for a laparoscopy;
* no previous PIPAC-procedures.

Enrolled patients are excluded from the analyses in case they did not receive a first ePIPAC-OX, e.g.:

* due to systemic metastases on baseline thoracoabdominal CT, or;
* due to non-access during first ePIPAC-OX, or;
* due to resectable disease during first ePIPAC-OX.

Importantly, enrolment is allowed for patients with an unresected primary tumour (if asymptomatic) and for patients in various lines of palliative treatment, including patients who refuse, have not had, or do not qualify for first-line palliative systemic therapy. All potentially eligible patients are discussed by a multidisciplinary team. Enrolled patients are informed about the potential consequences of postponing or discontinuing standard palliative treatment by a medical oncologist prior to enrolment.

• BACKGROUNDGiger-Pabst U, Tempfer CB. How to Perform Safe and Technically Optimized Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): Experience After a Consecutive Series of 1200 Procedures. J Gastrointest Surg. 2018 Dec;22(12):2187-2193. doi: 10.1007/s11605-018-3916-5. Epub 2018 Aug 21. PMID 30132291
• BACKGROUNDTempfer C, Giger-Pabst U, Hilal Z, Dogan A, Rezniczek GA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer. Arch Gynecol Obstet. 2018 Aug;298(2):243-257. doi: 10.1007/s00404-018-4784-7. Epub 2018 Jun 4. PMID 29869089
• BACKGROUNDGrass 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
• DERIVEDvan de Vlasakker VCJ, Lurvink RJ, Wassenaar EC, Rauwerdink P, Bakkers C, Rovers KP, Bonhof CS, Burger JWA, Wiezer MJ, Boerma D, Nienhuijs SW, Mols F, de Hingh IHJT. Comparing patient reported abdominal pain between patients treated with oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) and primary colorectal cancer surgery. Sci Rep. 2023 Nov 22;13(1):20458. doi: 10.1038/s41598-023-47510-0. PMID 37993560
• DERIVEDLurvink RJ, Rovers KP, Wassenaar ECE, Bakkers C, Burger JWA, Creemers GM, Los M, Mols F, Wiezer MJ, Nienhuijs SW, Boerma D, de Hingh IHJT. Patient-reported outcomes during repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for isolated unresectable colorectal peritoneal metastases in a multicenter, single-arm, phase 2 trial (CRC-PIPAC). Surg Endosc. 2022 Jun;36(6):4486-4498. doi: 10.1007/s00464-021-08802-6. Epub 2021 Nov 10. PMID 34757489
• DERIVEDRovers KP, Wassenaar ECE, Lurvink RJ, Creemers GM, Burger JWA, Los M, Huysentruyt CJR, van Lijnschoten G, Nederend J, Lahaye MJ, Deenen MJ, Wiezer MJ, Nienhuijs SW, Boerma D, de Hingh IHJT. Pressurized Intraperitoneal Aerosol Chemotherapy (Oxaliplatin) for Unresectable Colorectal Peritoneal Metastases: A Multicenter, Single-Arm, Phase II Trial (CRC-PIPAC). Ann Surg Oncol. 2021 Sep;28(9):5311-5326. doi: 10.1245/s10434-020-09558-4. Epub 2021 Feb 5.