Clinical trial NCT04231175: Dedicated MR Imaging vs Surgical Staging of Peritoneal Carcinomatosis in Colorectal Cancer
Official title: Dedicated MR Imaging vs Surgical Staging of Peritoneal Carcinomatosis in Colorectal Cancer Patients; a Multicenter Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Colorectal Cancer
Peritoneal Carcinomatosis
MRI
Keywords: Colorectal cancer
Peritoneal Carcinomatosis
MRI
Randomization
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2020-01-18
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multi center randomized trial
Primary purpose: DIAGNOSTIC

Brief summary: MRI is a potentially powerful tool to reliably determine the intra-abdominal tumor load and relations with intra-abdominal organs. In recent years diffusion weighted MRI has proven its value as a highly sensitive technique to detect small malignant disease in a wide variety of cancers \[1-3\]. However, literature concerning the clinical impact of detecting peritoneal metastases with MRI is very limited. Therefore, there is a need for a large randomized multicenter trial to determine whether dedicated MRI can be used as a selection tool for CRS-HIPEC candidates in daily practice.

Detailed description: HYPOTHESIS Staging with dedicated MRI will lead to a reduction of staging laparoscopies and explorative laparotomies in colorectal patients with PM to evaluate whether they may benefit from CRS-HIPEC

OBJECTIVES The goal is to perform a multicenter randomized study to compare a less invasive diagnostic workup ARM A (with MRI and surgical inspection reserved for borderline operable cases on MRI) to the standard diagnostic workup (ARM B, without MRI, with surgical staging to determine resectability based on a MDT decision) of patients with (suspected) peritoneal metastases. Surgical staging laparoscopies may largely be replaced by MRI (only reserved as a problem solver for borderline operable cases in ARM A). If it will be proven that MRI is an accurate, robust and cost-effective staging tool than this will result in a more patient friendly diagnostic workup with less futile surgical procedures.

STUDY DESIGN 4-year multicenter randomized controlled trial

STUDY POPULATION N=272 patients suspected of synchronous or metachronous peritoneal metastases of colorectal origin who are considered for CRS-HIPEC after CT imaging.

EXPERIMENTAL (ARM A) CRS-HIPEC candidates are selected based on MRI and only in borderline cases a surgical inspection will be performed

CONTROL (ARM B) Standard work-up including computed tomography and surgical inspection as appropriate (based on a MDT decision).

MAIN STUDY PARAMETERS/ENDPOINTS

Primary outcome:

Number of preventable unnecessary laparoscopies and explorative laparotomies.

NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT AND GROUP RELATEDNESS:

MRI is a standard diagnostic procedure without the use of radiation. The MR sequences, MR-contrast agents and Buscopan (to minimize peristaltic bowel movements) are all commonly used in daily clinical practice. In addition, patients will be asked to drink 1L of pineapple juice 1-2 hours before the MRI (to minimize signal in the bowel lumen and optimize image quality), which is standard procedure in many clinics for MRCP and MR enterography. By acting upon the MRI findings in the experimental arm A, could result into new risks as oppose to standard clinical practice. However by introducing the borderline group ('yellow light' group) to receive diagnostic laparoscopy will minimize the possibility of over-staging a patient that would have received a successful CRS/HIPEC in de control arm. In our internal pilot data of 87 patients considered for CRS/HIPEC, no patients with a PCI of above 24 ended up receiving successful CRS/HIPEC and only 4 of the 15 patients that could have been assigned to the borderline group (were the trail to have run at that time) received successful CRS/HIPEC.

Eligibility criteria: Inclusion Criteria:

* Patients with suspicion of colorectal peritoneal metastases and considered for CRS/HIPEC

  * Age ≥18 years
  * Written and signed informed consent
  * WHO 0-2
  * Able and willing to drink 1 liter of pineapple or blueberry juice

Exclusion Criteria:

* - Patients with contraindications for the MRI:
* Patients who have a heart pacemaker may not have an MRI scan
* Patients who have a metallic foreign body (metal sliver) in their body
* Patients with severe claustrophobia
* Ineligible to receive gadofosveset (Gadolinium) contrast (history of contrast allergy, impaired kidney function with a Glomerular Filtration Rate \<30 ml/min/1.73m2)
* Ineligible to receive Buscopan
* Allergy for pineapple juice and blueberry juice.
* Patients with clinical contraindications for CRS/HIPEC
* Patients with radiological contra-indications for CRS/HIPEC observed on CT thorax/abdomen
* Massive mesenteric or small bowel involvement which would lead to short bowel syndrome if adequately resected
* Extra-peritoneal metastases for which CRS/HIPEC is not justifiable (such as lung metastases, skeletal metastases, and liver metastases)
* Inoperable retroperitoneal lymphadenopathy
* Patients with a known additional malignancy, unless o treated with curative intent at least five years ago. in situ cancers, basal cell carcinoma of the skin or squamous cell carcinoma of the skin that have undergone potentially curative therapy within the past five years

Primary outcomes:
measure: Number of preventable unnecessary laparoscopies and explorative laparotomies defined as:
timeFrame: 4 weeks
measure: Number of preventable unnecessary laparoscopies and explorative laparotomies defined as
timeFrame: 4 weeks
Secondary outcomes:
measure: - Number of additional extra-peritoneal findings
timeFrame: 4 weeks
measure: - Number of early recurrences (with-in 6 months after R1 resection and HIPEC)
timeFrame: 6 months
measure: - Diagnostic performance of Peritoneal Cancer Index determined by MRI (MRI-PCI) to predict surgical Peritoneal Cancer Index (S-PCI).
timeFrame: 6 months
measure: - Inter-observer agreement between different readers for DW-MRI.
timeFrame: 6 months
measure: Incremental cost-effectiveness ratio
timeFrame: 6 months
measure: Quality of Life between diagnostic arms by EORTC-C30 -
timeFrame: 6 months
measure: Quality of Life between diagnostic arms by EQ5D5L
timeFrame: 6 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
Study officials:
affiliation: Antoni van Leeuwenhoek
name: Max Lahaye, PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Engbersen MP, Rijsemus CJV, Nederend J, Aalbers AGJ, de Hingh IHJT, Retel V, Lambregts DMJ, Van der Hoeven EJRJ, Boerma D, Wiezer MJ, De Vries M, Madsen EVE, Brandt-Kerkhof ARM, Van Koeverden S, De Reuver PR, Beets-Tan RGH, Kok NFM, Lahaye MJ. Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial. BMC Cancer. 2021 Apr 26;21(1):464. doi: 10.1186/s12885-021-08168-x.