To prospectively explore the feasibility safety, tolerability, preliminary efficacy, costs, and pharmacokinetic profile of repetitive ePIPAC-OX as a palliative monotherapy for isolated unresectable colorectal PM under controlled circumstances.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Metastases
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The number of patients with major toxicity (grade *3 according to the Common
Terminology Criteria for Adverse Events v4.0) up to four weeks after the last
procedure.
Secondary outcome
Secondary outcomes are:
* the environmental safety of ePIPAC-OX, based on air concentrations (measured
by RPS Analyse, Breda, Netherlands) and surface concentrations (measured by
Pharmacy, Cathari-na Hospital, Eindhoven, Netherlands) 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 [120], up to four
weeks after the last ePIPAC-OX;
* organ-specific toxicity, based on bone marrow, liver, and kidney functions
measured at dif-ferent time points (Table 1);
* major and minor postoperative complications, defined as grade *3 and grade *2
according to Clavien-Dindo [121], 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 af-ter 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 ra-diologists (JN, MLH) blinded to clinical outcomes
(classification is not defined a priori);
* histopathological tumour response, based on central review of collected
peritoneal biop-sies during each ePIPAC-OX, performed by two independent
pathologists (e.g. CJRH) blind-ed to clinical outcomes by using the Peritoneal
Regression Grading Score [122];
* cytological tumour response, based on collected ascites or peritoneal washing
cytology dur-ing 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 (Table 1);
* quality of life, extracted from questionnaires (EQ-5D-5L, QLQ-C30, QLQ-CR29)
at different time points (Table 1);
* 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 different time points (Table 1);
* 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.
Background summary
Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with
oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for
patients with isolated unresectable colorectal peritoneal metastases (PM) in
several centres worldwide. As a palliative monotherapy, repetitive ePIPAC-OX
may lead to intraperitoneal disease stabilisation with minimal treatment burden
and preservation of quality of life. However, hardly anything is known about
its feasibility, safety, tolerability, efficacy, costs, and pharmacokinetics in
this setting.
Study objective
To prospectively explore the feasibility safety, tolerability, preliminary
efficacy, costs, and pharmacokinetic profile of repetitive ePIPAC-OX as a
palliative monotherapy for isolated unresectable colorectal PM under controlled
circumstances.
Study design
Multicentre, open-label, single-arm, phase II study.
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)introduced.
Study burden and risks
Standard palliative (systemic) treatment seems to be less effective for
isolated unresectable colorectal PM compared to isolated unresectable
non-peritoneal colorectal metastases. Moreover, palliative systemic therapy is
associated with toxicity. As a palliative monotherapy, repetitive ePIPAC-OX may
therefore lead to intraperitoneal disease stabilisation with a low toxicity,
minimal treatment burden, and preservation of quality of life. If repetitive
ePIPAC-OX leads to unacceptable toxicity or progression, this is detected in a
sufficiently early stage by the frequent evaluations, after which standard
palliative (systemic) treatment is reintroduced. Conclusively, the
investigators feel that the potential benefits of participation outweigh the
potential burden and risks.
Michelangelolaan 2
Eindhoven 5623 EJ
NL
Michelangelolaan 2
Eindhoven 5623 EJ
NL
Listed location countries
Age
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 diagnos-tic 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 trans-aminsases <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
Not applicable. See inclusion criteria.
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2017-000927-29-NL |
| CCMO | NL60405.100.17 |
| Other | NTR (NTR6603), IRSCTN (ISRCTN89947480), ClinicalTrials.gov (NCT03246321) |