This study has been transitioned to CTIS with ID 2024-518570-13-00 check the CTIS register for the current data. Objectives of the phase II study (80 patients) are to explore the feasibility of accrual, the feasibility, safety, and tolerance of…
ID
Source
Brief title
Condition
- Peritoneal and retroperitoneal conditions
- Gastrointestinal neoplasms malignant and unspecified
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Endpoints of the phase II study are to explore the feasibility of accrual, the
feasibility, safety, and tolerance of perioperative systemic therapy, and the
radiological/histological response of colorectal PM to neoadjuvant systemic
therapy. The primary endpoint of the phase III study is 3-year overall
survival, which is hypothesised to be 50% in the control arm and 65% in the
experimental arm, thereby requiring 358 patients (179 in each arm).
Secondary outcome
Secondary endpoints are surgical characteristics, grade >=3 postoperative
morbidity, progression-free survival, disease-free survival, health-related
quality of life, costs, major systemic therapy related toxicity, and objective
radiological and histological response rates of colorectal PM to neoadjuvant
systemic therapy.
Background summary
Cytoreductive surgery with HIPEC (CRS-HIPEC) is a curative intent treatment for
patients with isolated resectable colorectal peritoneal metastases (PM).
Upfront CRS-HIPEC alone is the standard treatment in the Netherlands. The
addition of neoadjuvant and adjuvant systemic therapy (together: perioperative
systemic therapy) to CRS-HIPEC could have benefits and drawbacks. Potential
benefits are eradication of systemic micrometastases, preoperative
intraperitoneal tumour downstaging, elimination of post-surgical residual
cancer cells, and improved patient selection for CRS-HIPEC. Potential drawbacks
are preoperative disease progression and secondary unresectability for
CRS-HIPEC, systemic therapy related toxicity, increased postoperative
morbidity, decreased quality of life, and higher costs. Currently, there is a
complete lack of randomised studies that prospectively compare the oncological
efficacy of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC
alone. Notwithstanding this lack of evidence, perioperative systemic therapy is
widely administered to patients with isolated resectable colorectal PM.
However, administration and timing of perioperative systemic therapy vary
substantially between countries, hospitals, and guidelines. More importantly,
it remains unknown whether perioperative systemic therapy has an
intention-to-treat benefit in this setting. Therefore, this study randomises
patients with isolated resectable colorectal PM to receive either perioperative
systemic therapy (experimental arm) or upfront CRS-HIPEC alone (control arm).
Study objective
This study has been transitioned to CTIS with ID 2024-518570-13-00 check the CTIS register for the current data.
Objectives of the phase II study (80 patients) are to explore the feasibility
of accrual, the feasibility, safety, and tolerance of perioperative systemic
therapy, and the radiological and histological response of colorectal PM to
neoadjuvant systemic therapy. The primary objective of the phase III study (an
additional 278 patients) is to compare survival outcomes between both arms.
Secondary objectives are to compare surgical characteristics, major
postoperative morbidity, health-related quality of life, and costs between both
arms. Other objectives are to assess major systemic therapy related toxicity
and the objective radiological and histological response of colorectal PM to
neoadjuvant systemic therapy.
Study design
A multicentre, open-label, parallel-group, phase II-III, superiority study that
randomises eligible patients in a 1:1 ratio.
Intervention
At the discretion of the treating medical oncologist, perioperative systemic
therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of
capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant
cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly
neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI)
followed by either four 3-weekly (capecitabine) or six 2-weekly
(5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy.
Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI)
neoadjuvant cycles.
Study burden and risks
It is hypothesised that perioperative systemic therapy and CRS-HIPEC
(experimental arm) significantly improve the overall survival of patients with
isolated resectable colorectal PM compared to the current standard treatment
with upfront CRS-HIPEC alone (control arm). This potential overall survival
benefit should be weighed against the burden and risks of the experimental arm.
The most important potential burden/risks are: additional hospital visits for
the perioperative systemic therapy, preoperative disease progression and
secondary unresectability for CRS-HIPEC, increased postoperative complications
after CRS-HIPEC, toxicity of perioperative systemic therapy, and an intensified
and prolonged initial treatment that could decrease health-related quality of
life. The investigators feel that the potential overall survival benefit of the
experimental arm outweighs the burden and risks of participation. Patients in
both arms are given to possibility to give separate permission for receiving
questionnaires (costs, health-related quality of life) and for participation in
blood and tissue collection for translational research.
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;
* histological or cytological proof of PM of a non-appendiceal colorectal
adenocarcinoma with <=50% of the tumour cells being signet ring cells;
* resectable disease determined by abdominal computed tomography (CT) and a
diagnostic laparoscopy/laparotomy;
* no evidence of systemic colorectal metastases within three months prior to
enrolment;
* no systemic therapy for colorectal cancer within six months prior to
enrolment;
* no contraindications for CRS-HIPEC;
* no previous CRS-HIPEC;
* no concurrent malignancies that interfere with the planned study treatment or
the prognosis of resected colorectal PM.
Exclusion criteria
Patients are excluded in case of any comorbidity or condition that prevents
safe administration of the planned perioperative systemic therapy, determined
by the treating medical oncologist, e.g.:
* Inadequate bone marrow, renal, or liver functions (e.g. haemoglobin <6.0
mmol/L, neutrophils <1.5 x 109/L, platelets <100 x 109/L, serum creatinine >1.5
x ULN, creatinine clearance <30 ml/min, bilirubin >2 x ULN, serum liver
transaminases >5 x ULN);
* Previous intolerance of fluoropyrimidines or both oxaliplatin and irinotecan;
* Dehydropyrimidine dehydrogenase deficiency;
* Serious active infections;
* Severe diarrhoea;
* Stomatitis or ulceration in the mouth or gastrointestinal tract;
* Recent major cardiovascular events;
* Unstable or uncompensated respiratory or cardiac disease;
* Bleeding diathesis or coagulopathy;
* Pregnancy or lactation.
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 |
|---|---|
| EU-CTR | CTIS2024-518570-13-00 |
| EudraCT | EUCTR2016-001865-99-NL |
| ISRCTN | ISRCTN15977568;NCT02758951;NTR6301 |
| CCMO | NL57644.100.16 |