Treatment for liver metastases from colorectal cancer using a combination of therapies

Hepatic Arterial Infusion PUMP Chemotherapy Combined With Systemic Therapy Versus Systemic Therapy Alone as Induction Therapy for Initially Unresectable Colorectal Liver Metastases: a Randomised Controlled Trial

This study is testing if a new combination of treatments for liver cancer from colorectal cancer can help patients live longer compared to the standard treatment they would usually receive.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 306 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Netherlands Cancer Institute (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Amsterdam)
• Trial ID: NCT06857773 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining Hepatic Arterial Infusion Pump therapy with systemic therapy in patients with unresectable colorectal liver metastases who have not received prior chemotherapy. Participants will be randomly assigned to receive either the combined treatment or standard systemic therapy alone. The study aims to determine if the combined approach improves survival rates compared to the standard treatment. Both groups will undergo evaluations to assess the potential for surgical resection and quality of life assessments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed colorectal adenocarcinoma and unresectable liver metastases without extrahepatic disease.

Not a fit: Patients with extrahepatic metastases or those who have previously received systemic therapy for colorectal cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival outcomes for patients with unresectable colorectal liver metastases.

How similar studies have performed: Previous studies have shown promising results with similar approaches, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years.
* Histologically confirmed colorectal adenocarcinoma.
* Unresectable synchronous CRLM according to a National Liver Panel (CT-scan obtained ≤ 4 weeks prior to registration).
* No extrahepatic metastases. Patients with small (≤ 10 mm) extrahepatic lesions that are not clearly suspicious of metastases are eligible.
* No previous systemic therapy for colorectal cancer.
* Positioning of a catheter for HAIP chemotherapy is technically feasible based on imaging. The default site for the catheter insertion is the gastroduodenal artery (GDA). Accessory or aberrant hepatic arteries are no contra-indication for catheter implantation. The GDA should have at least one branch to the liver. Accessory or aberrant hepatic arteries should be ligated to allow for cross perfusion to the entire liver through intrahepatic shunts. Patients with celiac trunk stenosis are not eligible. Patients with both a replaced right and replaced left hepatic artery are not eligible.
* ECOG performance status 0 or 1.
* Life expectancy of at least 12 weeks.
* Known mutation status of RAS and BRAFV600E.
* Primary tumour in situ and resectable without neoadjuvant therapy.
* Patient is eligible for surgery.
* Patient is eligible for doublet chemotherapy.
* Laboratory requirements: i.e. adequate bone marrow, liver and renal function (obtained within 15 days prior to registration).

  * Hb ≥ 5.5 mmol/L
  * absolute neutrophil count (ANC) ≥1.5 x 109/L
  * platelets ≥100 x 109/L
  * total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
  * ASAT/AST ≤ 5 x ULN
  * ALAT/ALT ≤ 5 x ULN
  * alkaline phosphatase ≤ 5 x ULN
  * Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD (eGFR) ≥ 45 ml/min;
  * Prothrombin time or INR \< 1.5 x ULN, unless coumarin derivates are used. All patients using coumarin derivates will be treated with LMWH or DOAC instead.
* Before registration, written informed consent must be given and signed according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

* Prior hepatic radiation, resection, or ablation.
* Any malignancy, comorbidity or condition that interferes with the planned study treatment or the prognosis of CRLM, determined by the treating physician.
* History of prior malignancy except for the following: (a) malignancy treated with curative intent and with no evidence of active disease present within 3 years prior to inclusion, (b) curatively treated malignancies felt to be at low risk for recurrence by treating physician and MDT, (c) adequately controlled nonmelanomatous skin cancer, (d) adequately treated carcinoma in situ without current evidence of disease.
* Obstructive primary tumour requiring emergency surgery, primary tumour necessitating a multivisceral resection/abdominoperineal resection or a rectal tumour requiring preoperative short-course radiotherapy or chemoradiotherapy for local tumour control.
* MMR deficiency.
* DPD-deficiency.
* Pregnant or lactating women.
* 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.
* Organ allografts requiring immunosuppressive therapy.
* Serious non-healing wound, ulcer, or bone fracture.
* Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent excluding inhaled steroids).
* Known serious infections (uncontrolled or requiring treatment).
* History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP-SYST or standard systemic therapy.
* 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.
* Underlying liver disease including liver fibrosis and cirrhosis

Where this trial is running

Amsterdam

• Antoni van Leeuwenhoek-Netherland Cancer Institute — Amsterdam, Netherlands (Recruiting)

Study contacts

• Study coordinator: Koert FD Kuhlmann, MD PhD

Conditions Colorectal Neoplasms; Floxuridine; Liver Metastases; Vascular Access Device