Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy

Not Applicable

Not yet recruiting

• Conditions: Lung Metastases; Colorectal Cancer Metastatic
• Interventions: Procedure: Minimally invasive pulmonary metastasectomy; Radiation: Stereotactic ablative radiotherapy

• Registration Number: NCT05808790
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

COPPER is an international, multicenter, parallel-arm, phase III randomized controlled trial comparing two local treatment strategies (SABR or metastasectomy) for patients with an indication for local treatment for limited (max. three) colorectal pulmonary metastases

Detailed Description

The study is formally endorsed by the Dutch Society of Lung Surgery (NVvL), the Dutch Society of Cardiothoracic Surgery (NVT), the Dutch Society of Radiation Oncology (NVRO). The main objective of the proposed randomized trial is to compare efficacy of SABR to the efficacy of metastasectomy with regards to the primary endpoint (local recurrence free survival at 5 years) in patients with limited colorectal pulmonary metastases. This will determine the most effective local treatment modality. The investigators hypothesize that patients with limited colorectal pulmonary metastases will have non-inferior overall survival after pulmonary metastasectomy compared to SABR, however metastasectomy will result in superior local recurrence free survival at five years when compared to SABR. In addition, the investigators hypothesize that SABR is associated with lower morbidity, comparable quality of life and comparable health care costs compared to metastasectomy. Recurrent metastases are preferably treated by the index treatment to which the patient was randomized, local recurrent metastases are preferably treated by means of cross-over between both arms. Comparing metastasectomy to SABR for patients with colorectal pulmonary metastases will present the international community the evidence needed to better select patients for local radical treatment, while diminishing uncertainty for patients and care givers.

Study Timeline

• Study First Submitted: 2023-03-24
• Status Verified: 2023-04
• Study First Submitted QC: 2023-04-10
• Last Update Submitted: 2023-04-10
• Study First Posted: 2023-04-11
• Last Update Posted: 2023-04-11
• Study Start: 2024-01-01
• Primary Completion: 2030-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 394

Inclusion Criteria

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG)-Performance status 0 - 2
• Willing to provide informed consent
• Patients with 1 to 3 lung metastases from colorectal cancer eligible for both a minimally invasive surgical resection and SABR, as assessed by the multidisciplinary tumor board (MDT)
• Radically treated primary colorectal cancer
• Patient is able and willing to complete the quality-of-life questionnaires
• Previous liver metastases are radically treated with curative intent
• Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.

Exclusion Criteria

• Previous or present metastases outside liver or lungs
• Concurrent malignant cancer, or history of other malignant cancers within the past 5 years (excluding prespecified low-risk cancers)
• Hilar or mediastinal lymph node metastases
• Poor cardiopulmonary function test
• Inability to treat all colorectal metastases
• Surgical resection by means of a bilobectomy or pneumonectomy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Minimally invasive pulmonary metastasectomy	Minimally invasive pulmonary metastasectomy	Minimally invasive parenchymal sparing pulmonary metastasectomy Surgical approach by means of video-assisted thoracic surgery (VATS), robot-assisted (RATS), or uniportal VATS
Stereotactic ablative radiotherapy	Stereotactic ablative radiotherapy	Gross tumor volume = tumor visible on CT (+/- PET) No CTV margin will be added (Clinical target volume (CTV) = Gross target volume (GTV)) Planning Target Volume (PTV): GTV plus margins of 3-5mm (varying depending on site, motion, SABR delivery approach)

Primary Outcome Measures

Name	Time	Method
Local recurrence-free survival	From date of randomization through study completion, up to 10 years	Time from randomization to local recurrence or death from any cause

Secondary Outcome Measures

Name	Time	Method
Quality of life (QoL) assessment - EuroQoL (EQ-5D-5L)	5 years	\[0-5 for 5 dimensions, higher score = worse QoL\]
Quality of life assessment - Functional Assessment of Cancer Therapy: General (FACT-G)	5 years	\[27 questions in 4 subscales, higher score = better QoL\]
Health economic evaluation - Institute for Medical Technology Assessment (iMTA) - iMTA Medical Cost Questionnaire (iMCQ)	5 years	Medical costs \[Euro\]
Progression-free survival (PFS)	5 years	Time from randomization to disease progression at any site or death
Health economic evaluation - iMTA Productivity Cost Questionnaire (iPCQ)	5 years	Productivity costs \[Euro\]
Tumor patterns of failure	5 years	Local, regional and distant disease control based on surveillance imaging
Multiparameter flow cytometric analyses (FACS)	1 months	Peripheral blood mononuclear cell (PBMC) concentration
Overall survival (OS)	5 years	Time from randomization to death from any cause
Local recurrence rate (LRR) per tumor	5 years	Proportion of treated metastases with local recurrence
Rate of adverse events	2 years	Frequency of adverse events and serious adverse events

Trial Locations

Locations (1)

Amsterdam University Medical Center (AUMC); 🇳🇱 Amsterdam, Netherlands