COLLISION RELAPSE trial Recurrent colorectal liver metastases: repeat local treatment +/- neoadjuvant systemic therapy, a phase III prospective randomized controlled trial

• Register: CTIS
• Last refreshed on: 8 January 2025
• Main ID: CTIS2024-515341-41-01
• Date of registration: 19/11/2024
• Prospective Registration: Yes
• Primary sponsor: Stichting Amsterdam UMC
• Public title: COLLISION RELAPSE trial Recurrent colorectal liver metastases: repeat local treatment +/- neoadjuvant systemic therapy, a phase III prospective randomized controlled trial
• Scientific title: COLLISION RELAPSE trial Recurrent colorectal liver metastases: repeat local treatment +/- neoadjuvant systemic therapy, a phase III prospective randomized controlled trial
• Target sample size: 360
• Recruitment status: Not Recruiting
• URL: https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2024-515341-41-01
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Number of treatment arms in the trial:
• Phase: Human pharmacology (Phase I): No Therapeutic exploratory (Phase II): No Therapeutic confirmatory - (Phase III): Yes Therapeutic use - (Phase IV): Yes

Countries of recruitment

Netherlands

Contacts

• Name: Martijn Meijerink
• Affiliation: Stichting Amsterdam UMC

• Name: Martijn Meijerink
• Affiliation: Stichting Amsterdam UMC

Key inclusion & exclusion criteria

Inclusion criteria: Histological documentation of primary colorectal tumor, Life expectancy of at least 12 weeks, 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)., Written informed consent, Local treatment performed for initial CRLM, At least one recurrent CRLM eligible for local treatment (partial hepatectomy and/or thermal ablation, Maximum number of CRLM 5, Resection for resectable lesions considered possible obtaining negative resection margins (R0) and preserving adequate liver reserve, Resectability and ablatability should be re-confirmed with full exploration for hepatic, peritoneal and regional lymph node metastases, Age >18 years, Eastern Cooperative Oncology Group performance status (ECOG) 0-2, American Society of Anesthesiologists (ASA) grade 1-3
Exclusion criteria: No target lesions suitable for both resection and ablation, Severe allergy to contrast media not controlled with premedication, Substance abuse, medical, psychological or social conditions that may interfere with the subject’s participation in the study or evaluation of the study results, Microsatellite instability (MSI), Radical treatment unfeasible or unsafe (e.g. insufficient FLR), The presence of extrahepatic nodal or non-nodal metastases; see below for additional information regarding pulmonary nodules, Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites), Uncontrolled infections (> grade 2 NCI-CTC version 3.0), Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment, Immunotherapy = 6 weeks prior to the randomization, Chemotherapy = 6 weeks prior to the randomization, Progression on both oxaliplatin and irinotecan

Age minimum: 18
Age maximum: 65+
Gender: Female: yes Male: yes

Health Condition(s) or Problem(s) studied

Colorectal liver metastases

Therapeutic area: Diseases [C] - Neoplasms [C04]

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Name: Leucovorine Sandoz 15 mg, capsules, Product Code:PRD740255, Pharmaceutical Form: CAPSULE, Other descriptive name: , Strength: , Product Name: Fluorouracil Accord 50 mg/ml otopina za injekciju/infuziju, Product Code:PRD11641105, Pharmaceutical Form: SOLUTION FOR INJECTION/INFUSION, Other descriptive name: , Strength: , Product Name: Capecitabine Accord 150 mg film-coated tablets, Product Code:PRD1614128, Pharmaceutical Form: FILM-COATED TABLET, Other descriptive name: , Strength: , Product Name: Oxaliplatine Accord 5 mg/ml concentraat voor oplossing voor infusie, Product Code:PRD1785468, Pharmaceutical Form: CONCENTRATE FOR SOLUTION FOR INFUSION, Other descriptive name: , Strength: , Product Name: Irinotecan Accordpharma 20 mg/ml koncentrát pro infuzní roztok, Product Code:PRD11024074, Pharmaceutical Form: SOLUTION FOR INFUSION, Other descriptive name: , Strength:

Primary Outcome(s)

Main Objective: 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).

Primary end point(s): 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)

Secondary Objective: 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, 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, 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, Length of hospital stay, Pain assessment using visual analogue scale questionnaires (VAS; per procedure analysis: Assessed prior to, directly after and every three months after local treatment, 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, 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)

Secondary Outcome(s)

Secondary end point(s):Length of hospital stay

Secondary end point(s):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

Secondary end point(s):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

Secondary end point(s):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

Secondary end point(s):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)

Secondary end point(s):Pain assessment using visual analogue scale questionnaires (VAS; per procedure analysis: Assessed prior to, directly after and every three months after local treatment

Secondary end point(s):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

Secondary ID(s)

NCT05861505

2022-002214-17

Ethics review

Status: Authorised
Approval date: 11/12/2024
Contact: