exCalibur 3

exCalibur 3

EXCALIBUR3: Is a two-armed RCT randomizing between 1) liver-resection + systemic chemotherapy and 2) systemic chemotherapy – current standard treatment.

Including patients that have operable colorectal livermetastases (ablation may be used as adjunct) and extensive extrahepatic disease who have progressed on current line chemotherapy and are hence planned for next line treatment. (see inclusion/exclusion-criteria).

Following MDT potentially eligible patients will be evaluated at Rikshospitalet, Oslo University Hospital. If found eligible for inclusion and consent for participation patients will be randomized.

Liver-resection + systemic chemotherapy: Patients randomized to liver-resection will shortly following inclusion be scheduled for surgery. The operation will aim to resect/ablate avaliable liver-metastases. The operative technique will be decided by the operating surgeon/MDT. Following surgery the patient will start chemotherapy. Before start of chemotherapy a new baseline CT will be obtained. Blood-tests and clinical work-up will be obtained at their local-hospital when receiving chemotherapy and collected by the study-group. Every 8 weeks (4 cycles) a CT-chest + abdomen will be taken and evaluated by MDT,OUH. QoL will be taken every 8 weeks.

Systemic chemotherapy: Patients randomized to systemic chemotherapy will start next line chemotherapy at their local hospital. Blood-tests and clinical work-up will be obtained at their local-hospital when receiving chemotherapy and collected by the study-group. Every 8 weeks (4 cycles) a CT-chest + abdomen will be taken and evaluated by MDT,OUH. QoL will be taken every 8 weeks.

Inclusion and Exclusion criteria

1.1. Inclusion criteria

The trial seeks to include patients in whom liver resection is not considered standard of care.

All the following criteria must be present

  1. Verified adenocarcinoma in colon or rectum
  2. Liver metastases that are technically resectable (ablation can be used as an adjunct) without PVE, HVE or ALPPS, but judged in need of further (next line) chemotherapy based on insufficient response to at least one line of chemotherapy.

And either

a. Six or more liver metastases, with extra-hepatic disease that exceeds

i. 3 pulmonary metastases and/or
ii. radiologically positive liver hilar lymph nodes.

Or

b. Ten or more liver metastases with at least one of the following negative prognostic signs:

i. At least one lesion > 7 cm in diameter before chemotherapy
ii. CEA > 100 following chemotherapy
iii. KRAS and/or BRAF mutant primary tumour.
iv. Node positive primary tumour.

Or

c. Fifteen or more liver metastases

3.      ECOG 0/1
4.      Informed consent

 

1.2. Exclusion criteria

Any of the following criteria will exclude participation in the trial:

  1. Previous or current bone or CNS metastatic disease
  2. Peritoneal deposits/metastases that is not amenable to resection
  3. Any other reason why, in the opinion of the investigators, the patient should not participate.