COLLISION Trial - Colorectal Liver Metastases: Surgery vs Thermal Ablation

ColoRectal Cancer Clinical Trial

— COLLISION  

Official title:

COLLISION Trial - Colorectal Liver Metastases: Surgery vs Thermal Ablation, a Phase III Single-blind Prospective Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03088150
• Other study ID #: NL58551.029.16
• Status: Recruiting
• Phase: N/A
• Start date: July 13, 2017
• Est. completion date: December 2024

Study information

• Verified date: December 2022
• Source: Amsterdam UMC, location VUmc
• Contact: RS Puijk, MD
• Phone: 020 444 4444
• Email: interventieradiologie[@]vumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable colorectal liver metastases (≤3cm) and no extrahepatic disease.

Description:

Study design:

COLLISION is a single-blind prospective multi-center phase-III randomized controlled trial. We hypothesize that thermal ablation is non-inferior to surgery for the selected patient groups in terms of the primary objective (overall survival). The Cox proportional hazards model (1-sided; non-inferiority or superiority) is used for sample size calculations. Given the superior safety profile we consider a hazard ratio of 1.3 to represent the upper limit of non-inferiority (non-inferiority margin). An HR of 1.3 corresponds to a 56.5% chance of the ablated patients to die first ((P = HR/(1 + HR) = 1.3/(1 + 1.3) = 0.565 (56.5%)). With 3 years of patient accrual and five years of follow-up we will have reached 60% of events (death) in approximately 6.5 years (overall probability of event, pE =0.6). The calculated sample size therefore is 599 (NS).To account for a 10% drop-out ratio (NDO=69) prior to randomization and a 3% loss to follow-up (NLTFU=18) after randomization we need to include 687 patients (NI). A total number of 618 patients will be randomized (NR) into one of two arms: arm A will undergo surgical resection (n=309) and arm B thermal ablation (n=309) for appointed target lesions.

Study population:

Patients with ≥1 resectable and ablatable CRLM (≤3cm), no extrahepatic disease and a good performance status (WHO 0-2) are considered eligible. Supplementary resections for resectable lesions >3cm and thermal ablations for unresectable CRLM ≤3cm are allowed with a maximum number of CRLM of 10.

Intervention:

Eligible patients will be stratified into low-, intermediate- and high disease burden after assessment by an expert panel. The panel, consisting of at least two diagnostic radiologists, two interventional radiologists and two hepatobiliary and/or oncological surgeons, will appoint lesions that are resectable and ablatable as target lesions, resectable and unablatable lesions as unablatable lesions and ablatable but unresectable lesions as unresectable lesions. All unablatable lesions should be resectable and all unresectable lesions should be ≤3cm and ablatable.

With the exception of patients that are suitable for laparoscopic resection or percutaneous ablation (low disease burden), eligibility needs to be reconfirmed during the surgical procedure. Hereafter patients will be randomized to undergo surgical resection of the target lesions (allowing thermal ablation for additional unresectable lesions) or thermal ablation (allowing resection for additional unablatable lesions). For open procedures randomization will be performed shortly after surgical inspection and IOUS with the patient under general anaesthesia. Both the experimenter(s) and the participant will be unaware of the eventual treatment arm prior to the procedure; after the procedure the patient will remain unaware (single-blind).

Conferring to national guidelines follow-up will include imaging, laboratory tests including tumour markers (CEA) and clinical examination every 3 months for the first year and every 6 months hereafter. Follow-up cross-sectional imaging should include at least an abdominal ceCT or upper abdominal ceMRI at the given time-points. Participating centres are free to add 18F-FDG PET-CTs at specific time-points or to use alternating specific modalities, as long as the follow-up protocol is pre-approved by the trial coordinators and as long as follow-up imaging is identical for both treatment arms. Quality of life questionnaires will be assessed at baseline, every 3 months for the first year and every 6 months hereafter accordingly.

Patients with recurrences that are considered unsuitable for additional focal therapy will be re-referred to their medical oncologist to assess additional systemic chemotherapy. In the event of chemotherapeutic down-staging hereafter, focal therapy can be reconsidered.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 618
• Est. completion date: December 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Most important inclusion criteria:

• At least one CRLM size = 3 cm eligible for both surgical resection and thermal ablation (target lesions);

• Additional unresectable CRLM should be = 3 cm and ablatable (unresectable lesions);

• Additional unablatable CRLM should be resectable (unablatable lesions);

• Maximum number of CRLM 10;

• Resectability and ablatability should be re-confirmed intra-operatively by US plus full exploration for hepatic, peritoneal and regional lymph node metastases;

• ASA 1-3.

Most important exclusion criteria:

• No target lesions suitable for both resection and ablation;

• Radical treatment unfeasible or unsafe (e.g. insufficient FLR);

• The presence of extrahepatic nodal or non-nodal metastases;

• Immunotherapy or chemotherapy = 6 weeks prior to the procedure;

• Any surgical resection or focal ablative liver therapy for CRLM prior to inclusion

Related Conditions & MeSH terms

• ColoRectal Cancer
• Liver Metastases
• Liver Metastasis Colon Cancer
• Liver Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Surgery

Intervention

Procedure:
• Thermal ablation
Patients will undergo either radiofrequency ablation (RFA) or microwave ablation (MWA).
• Surgical resection
In case of randomization to surgical resection, the surgeon will remove all target lesions as well as all additional unablatable lesions.

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Center - location VUmc	Amsterdam	NH

Sponsors (2)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc	Medtronic - MITG

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	Counting from the date of randomization to the date of death of the patient or to the last day of follow-up.	5 years
Secondary	Disease free survival	The time from focal therapy to the time of events.	5 years
Secondary	Time to progression	The time from focal therapy to the time of events.	5 years