COLLISION RELAPSE Trial

NCT ID: NCT05861505

Last Updated: 2023-05-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-24
• Study Completion Date: 2028-05-01

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.

Conditions

Colorectal Cancer; Liver Metastases; Liver Metastasis Colon Cancer; Chemotherapy Effect; Surgery; Recurrence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Upfront repeat local treatment

Group Type: ACTIVE_COMPARATOR

Repeat local treatment

Intervention Type: OTHER

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).

Neoadjuvant systemic therapy followed by repeat local treatment

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

Repeat local treatment

Intervention Type: OTHER

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).

Interventions

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

Intervention Type: DRUG

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).

Intervention Type: OTHER

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

M.R. Meijerink

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Amsterdam UMC

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

M Dijkstra

Role: CONTACT

interventieradiologie@vumc.nl

+31(0)204444444

Facility Contacts

M Dijkstra

Role: primary

interventieradiologie@vumc.nl

+31(0)204444444

References

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 Randomized Controlled Trial. Cardiovasc Intervent Radiol. 2024 Feb;47(2):253-262. doi: 10.1007/s00270-023-03602-y. Epub 2023 Nov 9.

Reference Type: DERIVED

PMID: 37943351 (View on PubMed)

Other Identifiers

NL78220.029.21

Identifier Type: -

Identifier Source: org_study_id