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ID
Source
Brief title
Health condition
Colorectal Neoplasms; Cecal Neoplasms; Peritoneal Neoplasms; Peritoneal Metastases; Peritoneal Carcinomatosis; Colorectaal Carcinoom; Appendixcarcinoom; Peritoneale Metastasen; Peritonitis Carcinomatosa
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the number of patients with major toxicity, defined as grade ≥3 according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0, up to four weeks after the last ePIPAC-OX.
Secondary outcome
Secondary outcomes are:
the environmental safety of ePIPAC-OX, based on air concentrations and surface concentrations of oxaliplatin during the first three procedures, measured by atomic absorption spectrophotometry;
procedure-related characteristics of ePIPAC-OX (e.g. laparoscopic access, intraoperative complications, amount of adhesions, technical difficulties, operating time);
the number of procedures in each patient and reasons for discontinuation;
minor toxicity, defined as grade ≤2 according to CTCAE v4.0, up to four weeks after the last ePIPAC-OX;
organ-specific toxicity, based on bone marrow, liver, and kidney functions measured at baseline, each postoperative day, and four weeks after each ePIPAC-OX;
major and minor postoperative complications, defined as grade ≥3 and grade ≤2 according to Clavien-Dindo, respectively, up to four weeks after the last ePIPAC-OX;
hospital stay, defined as the number of days between ePIPAC-OX and initial discharge;
readmissions, defined as any hospital admission after initial discharge, up to four weeks after the last ePIPAC-OX;
radiological tumour response, based on central review of thoracoabdominal CT and DW-MRI at baseline and four weeks after each ePIPAC-OX, performed by two independent radiologists blinded to clinical outcomes (classification is not defined a priori);
histopathological tumour response, based on central review of collected peritoneal biopsies during each ePIPAC-OX, performed by two independent pathologists blinded to clinical outcomes by using the Peritoneal Regression Grading Score;
cytological tumour response, based on collected ascites or peritoneal washing cytology during each ePIPAC-OX;
macroscopic tumour response, based on PCI and ascites volume during each ePIPAC-OX;
biochemical tumour response, based on tumour markers measured at different time points;
quality of life, extracted from questionnaires (EQ-5D-5L, QLQ-C30, QLQ-CR29) at baseline and one and four weeks after each ePIPAC-OX;
costs, derived from the Dutch costing guidelines for health care research at the time of analysis, based on case report forms, hospital information systems, and questionnaires (iMTA PCQ, iMTA MCQ) at baseline and four weeks after each ePIPAC-OX;
progression-free survival, defined as the time between enrolment and clinical, radiological, or macroscopic progression, or death;
overall survival, defined as the time between enrolment and death.
Platinum concentrations in plasma and plasma ultrafiltrate (collected before ePIPAC-OX and 5, 10, 20, 30, 60, 120, 240, 360, and 1080 minutes after oxaliplatin injection), urine (collected before ePIPAC-OX and on postoperative days 1, 3, 5, and 7), and two pieces of normal peritoneum and two peritoneal metastases collected during each ePIPAC-OX.
Background summary
Background of study
Approximately a quarter of the patients who are diagnosed with colorectal cancer and metastases have their metastases in the peritoneum, the so called peritoneal metastases. The vast majority of these patients cannot be cured by surgery, frequently due to too many peritoneal metastases. These inoperable patients have a very short life expectancy. Nowadays, they are treated with chemotherapy through the veins. However, chemotherapy through the veins seems to be relatively ineffective against peritoneal metastases, probably because it does not reach the peritoneal metastases very well. Chemotherapy through the veins may also cause side effects that are sometimes severe. Recently, doctors developed PIPAC: a short laparoscopic operation during which chemotherapy is sprayed in the abdomen for 30 minutes every four to six weeks, directly against the peritoneal metastases. As a result, PIPAC may as effective against peritoneal metastases than chemotherapy through the veins, but it may cause less side effects because the chemotherapy stays in the abdomen. Although PIPAC indeed shows promising results in the first patients, little is still known about its safety, feasibility, tolerability, and efficacy.
Aim of study
To investigate whether PIPAC is a safe, feasible, tolerable, and potentially effective treatment for patients with inoperable peritoneal metastases of colorectal cancer.
Participants
Patients with inoperable peritoneal metastases of colorectal cancer without metastases elsewhere (e.g. liver, lung)
Treatment
Instead of chemotherapy through the veins, participants receive PIPAC every 6 weeks. PIPAC is a laparoscopic operation under general anaesthesia. During PIPAC, chemotherapy is sprayed in the abdomen for about 30 minutes. After PIPAC, patients stay in the hospital for one night. Four weeks after each PIPAC, patients visit the hospital for a scan and to evaluate whether PIPAC can be continued. PIPAC is continued until (1) the cancer grows, (2) PIPAC causes unacceptable side effects, or (3) PIPAC is technically not possible to perform. In case no further PIPAC is performed, restarting chemotherapy through the veins is discussed with the patient.
Potential risks for participants
PIPAC may cause side-effects. The most frequent potential side-effects are pain, nausea, fever, wound infection, diarrhea, obstipation, and minor damages to the kidney, liver, and bone marrow. These side-effects are mostly very mild. Moreover, the risk of side-effects of PIPAC is thought to be lower than the risk of side-effects of chemotherapy through the veins. Severe side-effects of PIPAC are extremely rare. The most important are a bowel perforation or a bleeding during PIPAC. So far, these severe side-effects have not been observed during PIPAC in patients with peritoneal metastases of colorectal cancer.
Potential benefits for participants
PIPAC may potentially be similarly effective against peritoneal metastases than chemotherapy through the veins, with a potential lower risk of side-effects. However, these potential benefits remain uncertain. The cancer may deteriorate at any moment during treatment with PIPAC.
Hypothesis of study
The investigators expect that PIPAC is a safe, feasible, tolerable, and potentially effective treatment for patients with peritoneal metastases of colorectal cancer.
Study objective
Repetitive ePIPAC-OX as a palliative monotherapy is a feasible, safe, tolerable, and potentially effective treatment for isolated unresectable colorectal peritioneal metastases, with low and predictable costs and a low systemic uptake of oxaliplatin.
Study design
See sections 'Primary outcome(s)' and 'secondary outcome(s)' above
Intervention
Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2 body-surface area [BSA]) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every six weeks. Four weeks after each procedure, patients undergo clinical, radiological, and biochemical evaluation. ePIPAC-OX is repeated until clinical, radiological, or macroscopic disease progression, after which standard palliative treatment is (re)considered.
Koen Rovers
Eindhoven 5602 ZA
The Netherlands
+31402396350
koen.rovers@catharinaziekenhuis.nl
Koen Rovers
Eindhoven 5602 ZA
The Netherlands
+31402396350
koen.rovers@catharinaziekenhuis.nl
Inclusion criteria
Eligible patients are adults who have:
a World Health Organisation (WHO) performance status of ≤1 and life expectancy >3 months;
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 transaminsases <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;
written informed consent.
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 in a multidisplinary team. Enrolled patients need to be informed about the potential consequences of postponing or discontinuing standard palliative treatment by a medical oncologist prior to enrolment.
Exclusion criteria
See inclusion criteria
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL6426 |
| NTR-old | NTR6603 |
| Other | EudraCT (2017-000927-29), Dutch competent authority (NL60405.100.17) : ClinicalTrials.gov (NCT03246321) |
| ISRCTN | ISRCTN89947480 |