COLLISION RELAPSE Trial

Официальное название

COLLISION RELAPSE Trial - Recurrent Colorectal Liver Metastases: Repeat Local Treatment +/- Neoadjuvant Systemic Therapy - a Phase III Prospective Randomized Controlled Trial

Обзор

The primary objective is to demonstrate superiority of neoadjuvant systemic therapy followed by repeat local treatment as compared to upfront repeat local treatment in patients with at least one locally treatable recurrent CRLM in the absence of extrahepatic disease.

Подробное описание

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.

Вмешательства

• Препарат Neoadjuvant systemic therapy (CAPOX+/-B FOLFOX+/-B FOLFIRI+/-B)
  Standard first line systemic treatment: CAPOX+/-B FOLFOX+/-B FOLFIRI+/-B CAPOX 4x (12 weeks) FOLFOX/FOLFIRI 6x (12 weeks) Maximum 4 cycles of CAPOX or 6 cycles of FOLFOX/FOLFIRI +/- bevacizumab regardless of the location of primary tumor or RAS/BRAF mutation
• Другое Repeat local treatment
  Choice of repeat local treatment is to the discretion of the local investigator, and may be selected on a per patient basis. The safety, feasibility and preferred type of surgical resection(s) is at the discretion of the liver surgeon (whether or not combined with thermal ablation). The safety, feasibility and preferred type of thermal ablation(s) is at the discretion of the interventional radiologist (whether or not combined with surgical resection).

Первичные конечные точки

• Overall survival (OS) per patient [Срок оценки: 5 years]

Вторичные конечные точки (9)

• Distant progression-free survival (DPFS) per patient [Срок оценки: 5 years]
• Local tumor progression-free survival (LTPFS) per patient and per tumor treated [Срок оценки: 5 years]
• Systemic therapy related toxicity per patient following neoadjuvant systemic therapy [Срок оценки: 5 years]
• Procedural morbidity and mortality per patient following repeat local treatment [Срок оценки: 5 years]
• Length of hospital stay per patient following repeat local treatment [Срок оценки: 5 years]
• Assessment of pain per patient [Срок оценки: 5 years]
• Quality of life (QoL) per patient [Срок оценки: 5 years]
• Quality-adjusted life years (QALY) per patient [Срок оценки: 5 years]
• Cost-effectiveness ratio (ICER) [Срок оценки: 5 years]

Критерии участия

Критерии включения

• Age >18 years
• Good performance status (ECOG 0-2 // ASA 1-3)
• Histological documentation of primary colorectal tumor
• Local treatment performed for initial CRLM
• New recurrence ≤12 months
• ≥1 locally treatable CRLM (resectable\* and/or ablatable)
• Total number of new CRLM ≤5
• Chemo-naïve or history of response to CAPOX/FOLFOX/FOLRIRI
• Life expectancy of at least 12 weeks
• Adequate bone marrow, liver and renal function
• Written informed consent Exclusion criteria
• Extrahepatic disease
• MSI/dMMR
• Radical local treatment unfeasible or unsafe (e.g. insufficient future liver volume)
• 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
• Immuno- or chemotherapy ≤ 6 weeks prior to the randomization
• 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

ECOG = Eastern Cooperative Oncology Group, ASA = American Society of Anesthesiologists, MSI = Microsatellite instability, dMMR = deficient mismatch repair

\* Resection for resectable lesions considered possible obtaining negative resection margins (R0) and preserving adequate liver reserve

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Amsterdam UMC — Amsterdam

Публикации

• Dijkstra M, Kuiper BI, Schulz HH, van der Lei S, Puijk RS, Vos DJW, Timmer FEF, Scheffer HJ, Buffart TE, van den Tol MP, Lissenberg-Witte BI, Swijnenburg RJ, Versteeg KS, Meijerink MR; COLLISION Trial Group. Recurrent Colorectal Liver Metastases: Upfront Local Treatment versus Neoadjuvant Systemic Therapy Followed by Local Treatment (COLLISION RELAPSE): Study Protocol of a Phase III Prospective Ra PMID 37943351

Идентификаторы

NCT: NCT05861505 · NL78220.029.21

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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