COLLISION RELAPSE Trial

Amsterdam UMC, location VUmc

Status and phase

Enrolling

Phase 3

Conditions

Chemotherapy Effect

Surgery

Liver Metastases

Liver Metastasis Colon Cancer

Recurrence

Colorectal Cancer

Treatments

Drug: Neoadjuvant systemic therapy (CAPOX+/-B FOLFOX+/-B FOLFIRI+/-B)

Other: Repeat local treatment

Study type

Interventional

Funder types

Other

Identifiers

NCT05861505

NL78220.029.21

Details and patient eligibility

About

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.

Full 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.

Enrollment

360 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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