CALCIUM FOLINATE PENTAHYDRATE for Colorectal liver metastases

Inclusion criteria

• {"criterion_text":"- Histological documentation of primary colorectal tumor\n- Life expectancy of at least 12 weeks\n- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: Version 3 May 12th 2023 45 of 140 o Hemoglobin ≥ 5.6 mmol/L; o Absolute neutrophil count (ANC) ≥ 1,500/mm3; o Platelet count ≥ 100*109/l; o Total bilirubin ≤ 1.5 times the upper limit of normal; o ALT and AST ≤ 2.5 x upper limit of normal (≤ 5 x upper limit of normal for subjects with liver involvement of their cancer); o Albumine > 30 g/l; o Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD ≥ 50 ml/min; o Prothrombin time or INR < 1.5 x ULN, unless coumarin derivates are used. Due to interactions with capecitabine, all patients using coumarin derivates will be treated with LMWH instead. o Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician).\n- Written informed consent\n- Local treatment performed for initial CRLM\n- At least one recurrent CRLM eligible for local treatment (partial hepatectomy and/or thermal ablation\n- Maximum number of CRLM 5\n- Resection for resectable lesions considered possible obtaining negative resection margins (R0) and preserving adequate liver reserve\n- Resectability and ablatability should be re-confirmed with full exploration for hepatic, peritoneal and regional lymph node metastases\n- Age >18 years\n- Eastern Cooperative Oncology Group performance status (ECOG) 0-2\n- American Society of Anesthesiologists (ASA) grade 1-3"}

Exclusion criteria

• {"criterion_text":"- No target lesions suitable for both resection and ablation\n- Severe allergy to contrast media not controlled with premedication\n- Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results\n- Microsatellite instability (MSI)\n- Radical treatment unfeasible or unsafe (e.g. insufficient FLR)\n- The presence of extrahepatic nodal or non-nodal metastases; see below for additional information regarding pulmonary nodules\n- Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites)\n- Uncontrolled infections (> grade 2 NCI-CTC version 3.0)\n- Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment\n- Immunotherapy ≤ 6 weeks prior to the randomization\n- Chemotherapy ≤ 6 weeks prior to the randomization\n- Progression on both oxaliplatin and irinotecan"}

Primary endpoints

• {"endpoint_text":"- Primary objective is to compare overall survival (OS) in both study arms, counting from the date of randomization to the date of death of the patient or to the last day of follow-up (censored)","definition_or_measurement_approach":"Overall survival (OS): time from randomization to date of death or to last day of follow-up (censored)."}

Secondary endpoints

• {"endpoint_text":"- Distant progression free survival (DPFS; per patient analysis): Overall DPFS is defined as the time from randomization to the time of disease progression (according to the RECIST 1.1 guideline (205)) or cancer related death (events), death related to other causes is considered a competing risk","definition_or_measurement_approach":"DPFS: time from randomization to disease progression per RECIST 1.1 or cancer-related death; other-cause death considered a competing risk."}
• {"endpoint_text":"- Local tumor progression free survival (LTPFS; per tumor and per patient analysis): Overall LTPFS is defined as the time from randomization to the time of local disease progression, new metastases (events), censoring the date of death from any cause (competing risk), completion ablations performed within 6 weeks for residual tumor are not considered events for the local tumor progression analysis","definition_or_measurement_approach":"LTPFS: time from randomization to local disease progression or new metastases; deaths censored as competing risk; ablations within 6 weeks for residual tumor not counted as events."}
• {"endpoint_text":"- Rate of adverse events and serious adverse events (AE and SAE; per procedure analysis), associated with both treatment arms; o Systemic therapy related toxicity is graded from 1 to 5 according to the CTCAE version 5.0, discussed in paragraph 9.4; o Procedural morbidity and mortality are graded from I to V according to the standard classification of surgical complications (206), discussed in paragraph 9.4","definition_or_measurement_approach":"AE/SAE rates per procedure; systemic therapy toxicity graded per CTCAE v5.0; procedural morbidity/mortality graded I–V per standard surgical complications classification."}
• {"endpoint_text":"- Length of hospital stay","definition_or_measurement_approach":"Length of hospital stay measured in days per procedure/admission."}
• {"endpoint_text":"- Pain assessment using visual analogue scale questionnaires (VAS; per procedure analysis: Assessed prior to, directly after and every three months after local treatment","definition_or_measurement_approach":"Pain measured by VAS prior to treatment, directly after, and every three months after local treatment."}
• {"endpoint_text":"- To determine quality of life in both treatment arms. Quality of life assessment using EORCT QLQ-C30, EQ-5D, and PRODISQ questionnaires (per procedure analysis): Assessed prior to, and Version 3 May 12th 2023 31 of 140 every three months after local treatment, assessed prior to, during and after neoadjuvant systemic therapy","definition_or_measurement_approach":"QoL assessed with EORTC QLQ-C30, EQ-5D and PRODISQ prior to treatment, every three months after local treatment, and before/during/after neoadjuvant systemic therapy."}
• {"endpoint_text":"- Direct and indirect total costs of care per treatment arm, quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) per treatment arm (per patient analysis)","definition_or_measurement_approach":"Health economic endpoints: direct/indirect costs, QALYs and ICER per treatment arm (per patient analysis)."}

Netherlands

Earliest CTIS Part Ii Submission Date

09-12-2024

Latest Decision Or Authorization Date

11-12-2024

Processing Time Days

2

Number Of Sites

2

Number Of Participants

360

Primary sponsor

Full Name

Stichting Amsterdam UMC

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands