COLLISION RELAPSE trial Recurrent colorectal liver metastases: repeat local treatment +/- neoadjuvant systemic therapy, a phase III prospective randomized controlled trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 360
- 试验地点
- 2
- 主要终点
- 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)
研究概览
简要总结
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).
详细描述
Study design: The COLLISION RELAPSE trial is a prospective multicenter phase III randomized controlled trial. The primary conducting center will be the Amsterdam UMC (Amsterdam, the Netherlands). We hypothesize that neoadjuvant systemic therapy followed by repeat local treatment is superior to upfront repeat local treatment for the selected patient groups in terms of the primary objective (OS). The Cox proportional hazards model (1-sided; superiority) and the PASKWIL criteria for adjuvant treatment for the benefit of OS from the Dutch Society of Medical Oncology are used for the sample size calculations. A total number of 360 patients will be randomized (NR) into one of two arms: arm A (control group) upfront repeat local treatment (n=180) and arm B (intervention group) 12 weeks of neoadjuvant systemic therapy followed by repeat local treatment (n=180).
Study population: Patients with a maximum of 5 recurrent new locally treatable CRLM within 12 months after initial curative intent local treatment of CRLM, no extrahepatic disease, and a good performance status (ECOG 0-2) are considered eligible. Both chemo-naïve patients and patients who did not progress on either oxaliplatin or irinotecan chemotherapy prior to the initial local treatment are eligible for inclusion.
Eligible patients will be stratified before randomization into two groups depending on the interval between initial local treatment and first detection of recurrent CRLM: recurrence within 6 months and recurrence between 6 and 12 months, RAS/BRAF mutation vs RAS/BRAF wildtype, prognostic risk score (low vs high risk, clinical risk score Fong et al. (83)) and previous chemotherapy versus no previous chemotherapy.
Intervention: Eligible patients will be randomized into one of two arms: arm A (control group) upfront repeat local treatment and arm B (intervention group) 12 weeks of neoadjuvant systemic therapy followed by repeat local treatment. Patients in arm B will receive maximum 4 cycles of CAPOX or 6 cycles of FOLFOX/FOLFIRI +/- bevacizumab regardless of the location of primary tumor or RAS/BRAF mutation. Choice of repeat local treatment is to the discretion of the local investigator, and may be selected on a per patient basis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
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 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)
次要结局
- 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)
研究者
Martijn Meijerink
Scientific
Stichting Amsterdam UMC