Systemic antitumor treatment with or without pressurized intraperitoneal aerosol chemotherapy (PIPAC) for colon peritoneal metastases – a multicentre phase II randomized trial (PIPOX02)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Cancerologie De L Ouest

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Jun 2025 → ongoing

Decision date (initial)

2024-10-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS Inca PHRC K 2021 (PHRCK23-053) · GAMIDA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Evaluate an improvement in progression free survival (PFS) between the group combining systemic treatments (chemotherapy + targeted therapy) and PIPAC and the group with systemic treatment alone in patients with peritoneal metastases in advanced colon cancer (PCI>15).

Secondary objectives 11

1. a) Overall survival (OS)
2. b) Impact on quality of life
3. c) Tolerance
4. d) Conversion rate to resectability
5. e) Peritoneal progression free survival (PPFS)
6. f) Obstruction-free survival (OFS)
7. g) Histological tumor response
8. h) Impact of baseline PCI on PFS in both arms
9. i) PIPAC arm: Impact on PFS according to initial extent of peritoneal metastases (assessed by PCI score)
10. j) Evaluate the prognostic value of the best histological result obtained at the 2nd PIPAC (for biopsies performed at the second PIPAC)
11. k) Relationship between mutational status and PFS in both groups

Conditions and MedDRA coding

Patients with newly diagnosed advanced peritoneal metastasis from colon and colorectal junction cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 1) Age ≥ 18 years;
2. 2) Written informed consent obtained from the patient before any study procedure;
3. 3) ECOG performance status of 0 to 2;
4. 4) Histopathologically confirmed colonic adenocarcinoma with synchronous or metachronous peritoneal metastasis (PM);
5. 5) Unresectable PM defined as any of the following: - PCI >15 - Extended small bowell involvement - Poor general condition contra-indication to a major abdominal surgery (eg: a complete cytoreductive surgery ), as decided by the medico-surgical team of the investigator’s site specialised in peritoneal carcinomatosis in charge of the patient.
6. 6) A surgical exploration performed less than 4 weeks before inclusion (if not, a laparoscopic exploration must be performed);
7. 7) Indication of first line systemic chemotherapy for advanced / metastatic colonic adenocarcinoma. Systemic chemotherapy in an adjuvant setting is allowed if completed more than 6 months before recurrence and without persistent oxaliplatin-induced neuropathy;
8. 8) No extended intraperitoneal adherences confirmed by surgical exploration (laparoscopy or laparotomy) in at least 9 out of 13 abdominal regions;
9. 9) Neutrophils count ≥ 1.5 x 109/L, platelet count ≥ 100 x109/L, hemoglobin ≥ 9 g/dL; Total bilirubin < 1.5 x ULN (upper limit of normal), ASAT and ALAT <3 x ULN, Alkaline phosphatase <1.5 x ULN, Serum creatinine < 1.5 x ULN;
10. 11) Men and women* must use effective contraceptive measures during the treatment and for at least 15 months after the last dose received; (* of childbearing age);
11. 10) Creatinine clearance ≥ 30 mL/min
12. 12) No known risk of irinotecan toxicity
13. 13) No Dihydropyrimidine dehydrogenase deficit (uracil blood Level <16ng/ml);
14. 14) Patient is willing and able to comply with the protocol for the duration of the study, including treatment and scheduled visits and examinations, including follow up;
15. 15) Patient has valid health insurance.

Exclusion criteria 30

1. 1) Other cancer treated within the last 3 years, with the exception of in situ cervical carcinoma or basocellular carcinoma;
2. 18) QT/QTc interval longer than 450 msec for men and longer than 470 msec for women on the inclusion ECG
3. 2) Rectal cancer primary (tumor <15 cm from the anal verge);
4. 3) Mutational status corresponding to microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR)
5. 4) Complete or partial bowel obstruction unresponsive to medical treatment;
6. 5) Extraperitoneal polymetastatic diseases. (Only oligometastatic1 diseases are allowed for inclusion) 1. 1oligo-metastatic disease as defined up to 3 liver metastases less than 5 cm in diameter and/or up to 3 lung nodules less than 10 mm in diameter and/or ovarian metastasis of any size.
7. 6) History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 6 months prior to enrolment;
8. 7) Active gastrointestinal bleeding;
9. 8) Severe ongoing infection;
10. 9) Clinically relevant and uncontrolled coronary heart disease, myocardial infarction within the past 12 months;
11. 19) Known history of hypersensibility to fluorouracil, folinic acid, irinotecan, oxaliplatin, capecitabine, cetuximab, panitumumab, bevacizumab or to any of their excipients, according to the SmPCs of these products.
12. 10) Uncontrolled arrhythmia;
13. 20) Concomitant treatment with brivudine, sorivudine or their chemically related analogues (according to the SmPC of fluorouracile)
14. 21) Live attenuated vaccines and for 6 months following cessation of chemotherapy (according to the SmPCs of fluorouracile and irinotecan);
15. 22) Concomitant use with St John's Wort (according to the SmPC of irinotecan);
16. 23) Severe renal insufficiency (creatinine clearance < 30 mL/min, according to the SmPC of capecitabine;
17. 24) History of allergy to red meat or tick bites or positive results of tests for IgE antibodies against cetuximab (α-1-3-galactose) (according to the SmPC of cetuximab);
18. 25) Interstitial lung disease (according to the SmPCs of cetuximab and panitumumab);
19. 26) Pulmonary fibrosis (according to the SmPC of panitumumab);
20. 27) Hypersensitivity to Chinese hamster ovary (CHO) cell products (according to the SmPC of bevacizumab)
21. 28) Pregnancy or breast-feeding period;
22. 29) Medical, geographical, sociological, psychological or legal conditions that would not permit the patient completing the study or signing the informed consent form.
23. 11) Uncontrolled hypertension;
24. 12) Inflammatory bowel disease;
25. 13) Ongoing non-healing wounds, ulcers or bone fractures;
26. 14) Relevant proteinuria (nephrotic syndrome); arterial thromboembolisms or severe haemorrhages within 6 months before study enrolment (except a bleeding tumour before tumour resection surgery) precluding the use of anti-VEGF drug;
27. 15) Haemorrhagic diathesis or thrombotic tendency;
28. 16) Peripheral neuropathy oxaliplatin-related according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0;
29. 17) No reversible electrolyte disorders such as hypokalemia, hypocalcemia or hypomagnesemia.
30. 30) Appendix cancer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (PFS) is defined as the time (in months) from randomisation until the date of progression or death from any cause.

Secondary endpoints 11

1. a) Overall survival (OS) defined as the time relapsed between randomisation and death from any cause
2. b) EORTC QLQ-C30 (Appendix 12) and the EORTC QLQ-CR29 (Appendix 13) questionnaires
3. c) • Toxicities ≥ grade 3 related to chemotherapy (IV, PO or PIPAC), targeted therapy and abdominal surgery (laparoscopy, PIPAC procedure, biopsies, CRS) assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (Appendix 10); • Toxicities ≥ grade 3 related to abdominal surgery as assessed by the CLAVIEN DINDO score (Appendix 11). • Toxicities of any grade about peripheral neuropathy assessed according to the Common Terminology Criteria for Adverse Events (CTC
4. d) Resection rate defined as proportion of patients who proceed to secondary cytoreductive surgery CC0 or CC1 with or without hyperthermic intraperitoneal chemotherapy (HIPEC)
5. e) Peritoneal progression free survival defined as the time between the date of randomisation and the date of peritoneal progression or death from any cause.
6. f) OFS is defined as the time between the date of randomisation and the appearance of gastrointestinal obstruction requiring medication with high dose of corticosteroïd (> 1mg/kg) or intervention as nasogastric decompression, intraluminal stenting, surgical bypass, or decompression stomy (gastrostomy or ileo/colostomy) or death.
7. g) Peritoneal regression grading score (PRGS) (Appendix 6) on biopsies performed at surgical exploration in both groups, and systematically during 1st and 2nd PIPAC procedure.
8. h) PCI < 20 and PCI ≥ 20
9. i) PFS benefit of adding PIPAC to systemic chemotherapy after baseline PCI: PCI < 20 and PCI ≥ 20
10. j) PFS according to PRGS (1-2 vs 3-4) after the 2nd PIPAC
11. k) PFS following tumor mutation status (KRAS wt vs KRAS mt and BRAF wt vs BRAF mt)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Cancerologie De L Ouest

Sponsor organisation

Institut De Cancerologie De L Ouest

Address

Boulevard Jacques Monod

City

Saint-Herblain Cedex

Postcode

44805

Country

France

Scientific contact point

Organisation

Institut De Cancerologie De L Ouest

Contact name

Frédric DUMONT

Public contact point

Organisation

Institut De Cancerologie De L Ouest

Contact name

Emilie DEBEAUPUIS

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications