Adjuvant hepatic arterial infusion pump chemotherapy after resection of colorectal liver metastases in patients with a low clinical risk score – a randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04]

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512850-10-00

EudraCT number

2018-001696-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to compare the efficacy of surgery and adjuvant HAIP chemotherapy, assessed by progression free survival (PFS), with surgery alone in patients with resectable colorectal liver metastases with a low clinical risk score (CRS 0-2).

Secondary objectives 9

1. To compare overall survival between the two arms
2. To compare progression free survival in the liver between the two arms.
3. To compare postoperative complications between the two arms
4. To compare adverse events between the two arms
5. To compare quality of life between the two arms.
6. To evaluated the cost effectiveness of HAIP chemotherapy expressed by the incremental cost-effectiveness ratio.
7. To determine whether CT angiography can replace a nuclear medicine scan to rule out extrahepatic perfusion of the pump.
8. To identify predictive biomarkers for the efficacy of HAIP chemotherapy.
9. To establish the systemic pharmacokinetic profile of intra-arterial administration of floxuridine.

Conditions and MedDRA coding

Resectable colorectal rectal metastases without extrahepatic disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age ≥ 18 years
2. ECOG performance status 0 or 1
3. Clinical Risk Score (CRS) of 0-2
4. Histologically confirmed colorectal cancer (CRC)
5. Radiologically confirmed CLM amenable for resection or open ablation
6. Positioning of a catheter for HAIP chemotherapy is technically feasible based on a CT with early arterial phase with 1mm cuts
7. Adequate bone marrow, liver and renal function conducted within 15 days prior to inclusion

Exclusion criteria 17

1. Presence of extrahepatic disease (including positive portal lymph nodes) at the time of liver resection or any time since CRC diagnosis. Patients with small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases are eligible.
2. Second primary malignancy except in situ carcinoma of the cervix, adequately treated non-melanoma skin cancer, or other malignancy treated at least 5 years previously without evidence of recurrence. • Prior hepatic radiation, resection, or ablation
3. Prior hepatic radiation, resection, or ablation
4. CLM requiring two-staged resections.
5. Liver-first resections
6. Postoperative radiation of non-surgically treated (resection or open ablation) CLM
7. (Partial) portal vein thrombosis
8. Known DPD-deficiency (heterozygous or homozygous)
9. Pregnant women or lactating women
10. History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP chemotherapy
11. Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator
12. Serious, non-healing wound, ulcer, or bone fracture
13. Organ allografts requiring immunosuppressive therapy
14. Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent excluding inhaled steroids)
15. Serious infections (uncontrolled or requiring treatment). • Participation in another interventional study for CLM with survival as outcome.
16. Participation in another interventional study for CLM with survival as outcome.
17. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. progression free survival (PFS)

Secondary endpoints 9

1. Overall survival
2. Progression free survival in the liver
3. Postoperative complications
4. adverse events
5. Quality of life
6. Cost effectiveness
7. the accuracy of CT angiography to detect extrahepatic perfusion
8. pharmacokinetic profile of intra-arterial administration of floxuridine will
9. predictive biomarkers for the efficacy of HAIP chemotherapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Prof.dr. Groot Koerkamp

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Prof.dr. Groot Koerkamp

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications