EXtended CriteriA Treatment for LIver Metastases and Heavy Tumour BURden

NCT04840186 | Suspended Phase 2 DMC

• 1 other identifier: 167434
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with multiple colorectal liver metastases that progress on 1st line chemotherapy have a very dismal prognosis, and their options are few. Resections are regularly performed although this is only supported by anecdotal evidence for this patient group. We want to assess whether resections actually confer benefit as compared to 2nd line chemotherapy alone, in a randomized controlled trial.

Conditions

Liver Metastases; Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Median overall survival

  Primary endpoint is median survival after two years to see if the survival is different in the two groups.

  2years

Secondary Outcomes (3)

• Quality of Life

  EQ-5D-5L will be obtained at inclusion, week 6,12,18,24,36,48,60,72,84,96,108.

• Progression free survival PFS

  From inclusion to sign of progresion, tentatively less than 14months.

• Quality of life

  EORTC QLQ-C30 will be obtained at inclusion, week 6,12,18,24,36,48,60,72,84,96,108.

Study Arms (2)

2nd line chhemotherapy

ACTIVE COMPARATOR

Patients in this arm will be receiving the standard care which is 2nd line chemotherapy. Type of chemotherapy determined by treating oncologist.

Drug: 2nd line chemotherapy

2nd line chemotherapy + resection

ACTIVE COMPARATOR

Patients in this arm will be treated with liver resection and/or ablation at Oslo University Hospital followed by adjuvant 2nd line chemotherapy. Type of chemotherapy is determined by treating oncologist.

Procedure: Liver-resection or ablation; Drug: 2nd line chemotherapy

Interventions

Liver-resection or ablation PROCEDURE

Liver-resection of colorectal liver metastasis. Ablation can be used as adjunct to surgery.

2nd line chemotherapy + resection

2nd line chemotherapy DRUG

2nd line chemotherapy. Type of chemotherapy is determined by treating oncologist

2nd line chemotherapy + resection; 2nd line chhemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Verified adenocarcinoma in colon or rectum
• 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 i. def: \>3 pulmonary metastases/radiologically positive non-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 a full cycle of chemotherapy)?? iii. KRAS and/or BRAF mutant primary tumour. iv. Node positive primary tumour. Or c. Fifteen or more liver metastases
• ECOG 0/2
• Informed consent

You may not qualify if:

• Any of the following criteria will exclude participation in the trial:
• New liver metastases emerging during completed chemotherapy.
• a. These patients may be included if they undergo a complete cycle of next line chemotherapy without new liver metastases emerging.
• Previous or current bone or CNS metastatic disease
• Any other reason why, in the opinion of the investigators, the patient should not participate.

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, Oslo County, 0372, Norway

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Hepatectomy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Kristoffer Lassen, MD PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Multicentre RCT with two parallell arms. One with second line chemotherapy (standard care) and the other with second line chemotherapy + resection. We estimate an overall survival of 12 months in the standard care group. We aim to decide whether resections added to chemotherapy can increase this to 24 months. A two-sided parallel-group test of proportions to answer this with a power of 0.80 and an alpha of 0.15, will require 28 completed patients per group to show superiority for resections. Adding 11 % for a modified intention-to-treat analysis, we aim to randomise a total of 62 patients, i.e. 31 patients per group.

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 9, 2021
• Study Start: March 23, 2021
• Primary Completion: December 1, 2024
• Study Completion: March 1, 2026
• Last Updated: November 12, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

NO (1)