Clinical trial NCT05861505: COLLISION RELAPSE Trial
Official title: COLLISION RELAPSE Trial - Recurrent Colorectal Liver Metastases: Repeat Local Treatment +/- Neoadjuvant Systemic Therapy - a Phase III Prospective Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Colorectal Cancer
Liver Metastases
Liver Metastasis Colon Cancer
Chemotherapy Effect
Surgery
Recurrence
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2023-05-17
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion criteria

* 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

Primary outcomes:
measure: Overall survival (OS) per patient
timeFrame: 5 years
Secondary outcomes:
measure: Distant progression-free survival (DPFS) per patient
timeFrame: 5 years
measure: Local tumor progression-free survival (LTPFS) per patient and per tumor treated
timeFrame: 5 years
measure: Systemic therapy related toxicity per patient following neoadjuvant systemic therapy
timeFrame: 5 years
measure: Procedural morbidity and mortality per patient following repeat local treatment
timeFrame: 5 years
measure: Length of hospital stay per patient following repeat local treatment
timeFrame: 5 years
measure: Assessment of pain per patient
timeFrame: 5 years
measure: Quality of life (QoL) per patient
timeFrame: 5 years
measure: Quality-adjusted life years (QALY) per patient
timeFrame: 5 years
measure: Cost-effectiveness ratio (ICER)
timeFrame: 5 years
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
References: