IRINOTECAN HYDROCHLORIDE TRIHYDRATE for Colorectal adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years.\n- ECOG performance status 0 or 1.\n- Life expectancy of at least 12 weeks.\n- Histologically confirmed colorectal adenocarcinoma\n- Indication for first or second line systemic therapy, confirmed in a multidisciplinary meeting.\n- Potentially resectable (i.e. unresectable and upfront resectable CRLM with indication for neoadjuvant systemic therapy), confirmed in a multidisciplinary meeting and radiologically on (PET) CT thorax/abdomen and/or MRI obtained ≤ 4 weeks prior to registration.\n- Positioning of a catheter for HAIP chemotherapy is technically feasible confirmed in the multidisciplinary liver meeting 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.\n- Indication and eligibility for abdominal surgery confirmed in a multidisciplinary meeting, e.g. primary tumour resection, stoma revision/reversal and diagnostic surgery.\n- In case of primary tumour in situ: tumour should be (potentially) resectable, confirmed in a multidisciplinary meeting.\n- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 15 days prior to inclusion: o Hb ≥ 5.5 mmol/L o Absolute neutrophil count (ANC) ≥1.5 * 109/L o Platelets ≥100 * 109/L o Total bilirubin < 1.5 mg/dL o ASAT ≤ 5 * times the upper limit of normal (ULN) o ALAT ≤ 5 * ULN o Alkaline phosphatase ≤ 5 * ULN o (estimated) glomerular filtration rate (eGFR) > 45 ml/min.\n- Before patient registration, written informed consent must be given and signed according to ICH-GCP, and national/local regulations"}

Exclusion criteria

• {"criterion_text":"- Extrahepatic metastases. Confirmed with CT thorax/abdomen obtained ≤ 4 weeks prior to registration. Patients with small (≤ 1 cm) extrahepatic lesions that are not clearly suspicious of metastases are eligible.\n- Prior hepatic radiation, resection (other than biopsy), or ablation.\n- Concurrent malignancies that interfere with the planned study treatment or the prognosis of CRLM.\n- Participation in other clinical trials interfering with the study treatment as judged by the treating physician.\n- Dihydropyrimidine dehydrogenasedeficiency (DPD deficiency).\n- Pregnant or lactating women.\n- 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.\n- Organ allografts requiring immunosuppressive therapy.\n- Serious, non-healing wound, ulcer, or bone fracture.\n- Chronic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisolone equivalent excluding inhaled steroids).\n- Serious infections (uncontrolled or requiring treatment).\n- History of psychiatric disability judged by the investigator to potentially hamper compliance with the study protocol and follow-up schedule.\n- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint of this feasibility study is feasibility, presented as the percentage of in-cluded patients scheduled for surgery which can be treated with at least 2 cycles of HAIP chemotherapy combined with concomitant systemic chemotherapy.","definition_or_measurement_approach":"Feasibility presented as the percentage of included patients scheduled for surgery who can be treated with at least 2 cycles of HAIP chemotherapy combined with systemic chemotherapy. (Translation defines feasibility as at least 70% of included patients scheduled for surgery being treated with ≥2 cycles of the combination.)"}

Secondary endpoints

• {"endpoint_text":"- Safety: postoperative complications (defined according to Clavien-Dindo surgical complications score. Complications of Clavien-Dindo grade 3 or higher are recorded for the first 90 days after surgery. Postoperative complications include those related to the HAIP implantation. Postoperative mortality id defined as any death during hospitalization or within 90 days from surgery.","definition_or_measurement_approach":"Postoperative complications recorded per Clavien-Dindo surgical complications score; grade 3+ recorded for first 90 days after surgery. Postoperative mortality defined as any death during hospitalization or within 90 days from surgery."}
• {"endpoint_text":"- Safety: Drug treatment toxicity Toxicity grade 3 or higher will be recorded from the time of study inclusion according to the CTCAE version 5.0","definition_or_measurement_approach":"Drug treatment toxicity graded per CTCAE v5.0; toxicity grade 3 or higher recorded from inclusion."}
• {"endpoint_text":"- Safety: Other adverse events Treatment related serious adverse events (SAE) and adverse events (AE) of grade 3 or higher will be collected continuously from the time of study inclusion until the end of combined chemotherapy.AE are followed up until the event is either resolved or adequately explained, even after the patient has completed his/her study treatment. Nature and duration of any hospitalization, treatment of any AE, and nature and duration of any outpatient care will be recorded.","definition_or_measurement_approach":"Treatment-related SAEs and AEs grade 3+ collected continuously from inclusion until end of combined chemotherapy; AEs followed until resolution or explanation; hospitalisations and treatments recorded."}
• {"endpoint_text":"- Response rates of CRLM will be measured according to RECIST 1.1 criteria version 5.0","definition_or_measurement_approach":"Response of colorectal liver metastases measured per RECIST 1.1 criteria (version 5.0)."}
• {"endpoint_text":"- PFS will be defined from inclusion date until disease progression.","definition_or_measurement_approach":"Progression-free survival measured from inclusion date to documented disease progression."}
• {"endpoint_text":"- OS will be defined from inclusion date until death.","definition_or_measurement_approach":"Overall survival measured from inclusion date until death from any cause."}
• {"endpoint_text":"- Conversion rate is defined as the percentage of patients in whom CRLM convert from an unresectable to a resectable state and undergo surgical treatment with curative intent. Possibility of local treatment is at the discretion of the multidisciplinary liver panel.","definition_or_measurement_approach":"Conversion rate = percentage of patients whose CRLM convert from unresectable to resectable and who undergo curative-intent surgery; local treatment decisions per multidisciplinary liver panel."}

Netherlands

Earliest CTIS Part Ii Submission Date

14-06-2024

Latest Decision Or Authorization Date

27-11-2024

Processing Time Days

166

Number Of Sites

2

Number Of Participants

31

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands