E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with resectable colorectal liver metastases |
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E.1.1.1 | Medical condition in easily understood language |
Patients with resectable metastases of colorectal cancer in the liver |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to compare the efficacy of surgery and adjuvant HAIP chemotherapy to surgery alone in patients with resectable colorectal liver metastases with a low clinical risk score (CRS 0-2 point). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to compare postoperative complications, adverse events, quality of life, and costs between the two arms. Another secondary objective is to determine whether CT angiography can replace a nuclear medicine scan to rule out extrahepatic perfusion of the pump. Next, we aim to identify predictive biomarkers for the efficacy of HAIP chemotherapy and study the pharmacokinetic profile of floxuridine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 18 years.
• ECOG performance status 0 or 1.
• Clinical Risk Score (CRS) of 0-2
• Histologically confirmed colorectal cancer (CRC)
• Radiologically confirmed CLM amenable for resection or open ablation
• Positioning of a catheter for HAIP chemotherapy is technically feasible based on a CT excellent arterial phase
• Adequate bone marrow, liver and renal function conducted within 15 days prior to inclusion |
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E.4 | Principal exclusion criteria |
• 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.
• 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.
• CLM requiring two-staged resections.
• Liver-first resections.
• Postoperative radiation of non-surgically treated (resection or open ablation) CLM
• (Partial) portal vein thrombosis.
• DPD-deficiency (heterozygous or homozygous)
• Pregnant women or lactating women.
• History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP chemotherapy.
• 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).
• Serious infections (uncontrolled or requiring treatment).
• Current or recent (within the 28 days prior to randomization) treatment with another investigational drug or participation in another investigational study.
• 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is progression free survival (PFS). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
One year after inclusion of the last patient |
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E.5.2 | Secondary end point(s) |
Secondary endpoints include OS, PFS in the liver, postoperative complications, adverse events, quality of life, and cost effectiveness. Also, the accuracy of CT angiography to detect extrahepatic perfusion will be evaluated. Next, we aim to identify predictive biomarkers for the efficacy of HAIP chemotherapy. Furthermore, the pharmacokinetic profile of intra-arterial administration of floxuridine will be established. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After inclusion of the last patient, one year after the inclusion of the last patient and 6 years after the inclusion of the last patient |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Predictive value of biomarkers |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Resection alone (= standard of care) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |