COPPER: Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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 |
Procedure: Minimally invasive pulmonary metastasectomy
Surgical margin is equal to tumor size, if possible The goal is a parenchymal-sparing resection
Other Names:
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| Experimental: 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) |
Radiation: Stereotactic ablative radiotherapy
Depending on tumor location, 54 Gy in 3 fractions, 55 Gy in 5 fractions, 60 Gy in 8 fractions.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- Overall survival (OS) [5 years]
Time from randomization to death from any cause
- Progression-free survival (PFS) [5 years]
Time from randomization to disease progression at any site or death
- Local recurrence rate (LRR) per tumor [5 years]
Proportion of treated metastases with local recurrence
- 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]
- 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
- Rate of adverse events [2 years]
Frequency of adverse events and serious adverse events
- Multiparameter flow cytometric analyses (FACS) [1 months]
Peripheral blood mononuclear cell (PBMC) concentration
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years
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Eastern Cooperative Oncology Group (ECOG)-Performance status 0 - 2
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Willing to provide informed consent
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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)
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Radically treated primary colorectal cancer
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Patient is able and willing to complete the quality-of-life questionnaires
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Previous liver metastases are radically treated with curative intent
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Histologically confirmed malignancy with metastatic disease detected on imaging. Biopsy of metastasis is preferred, but not required.
Exclusion Criteria:
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Previous or present metastases outside liver or lungs
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Concurrent malignant cancer, or history of other malignant cancers within the past 5 years (excluding prespecified low-risk cancers)
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Hilar or mediastinal lymph node metastases
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Poor cardiopulmonary function test
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Inability to treat all colorectal metastases
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Surgical resection by means of a bilobectomy or pneumonectomy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Amsterdam University Medical Center (AUMC) | Amsterdam | Netherlands | 1081 HZ |
Sponsors and Collaborators
- Amsterdam UMC, location VUmc
- Dutch Cancer Society
Investigators
- Principal Investigator: Martijn van Dorp, MD, AUMC
Study Documents (Full-Text)
None provided.More Information
Publications
- Devlin NJ, Krabbe PF. The development of new research methods for the valuation of EQ-5D-5L. Eur J Health Econ. 2013 Jul;14 Suppl 1(Suppl 1):S1-3. doi: 10.1007/s10198-013-0502-3. No abstract available.
- Franks KN, McParland L, Webster J, Baldwin DR, Sebag-Montefiore D, Evison M, Booton R, Faivre-Finn C, Naidu B, Ferguson J, Peedell C, Callister MEJ, Kennedy M, Hewison J, Bestall J, Gregory WM, Hall P, Collinson F, Olivier C, Naylor R, Bell S, Allen P, Sloss A, Snee M. SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection. Eur Respir J. 2020 Nov 12;56(5):2000118. doi: 10.1183/13993003.00118-2020. Print 2020 Nov.
- Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 Jan;13(1):8-10. doi: 10.1200/JCO.1995.13.1.8. No abstract available.
- Lodeweges JE, Klinkenberg TJ, Ubbels JF, Groen HJM, Langendijk JA, Widder J. Long-term Outcome of Surgery or Stereotactic Radiotherapy for Lung Oligometastases. J Thorac Oncol. 2017 Sep;12(9):1442-1445. doi: 10.1016/j.jtho.2017.05.015. Epub 2017 May 30.
- Nelson DB, Tayob N, Nguyen QN, Erasmus J, Mitchell KG, Hofstetter WL, Sepesi B, Antonoff MB, Mehran RJ. Local failure after stereotactic body radiation therapy or wedge resection for colorectal pulmonary metastases. J Thorac Cardiovasc Surg. 2019 Oct;158(4):1234-1241.e16. doi: 10.1016/j.jtcvs.2019.02.133. Epub 2019 May 11.
- Nicosia L, Franceschini D, Perrone-Congedi F, Casamassima F, Gerardi MA, Rigo M, Mazzola R, Perna M, Scotti V, Fodor A, Iurato A, Pasqualetti F, Gadducci G, Chiesa S, Niespolo RM, Bruni A, Alicino G, Frassinelli L, Borghetti P, Di Marzo A, Ravasio A, De Bari B, Sepulcri M, Aiello D, Mortellaro G, Sangalli C, Franceschini M, Montesi G, Aquilanti FM, Lunardi G, Valdagni R, Fazio I, Scarzello G, Corti L, Vavassori V, Maranzano E, Magrini SM, Arcangeli S, Gambacorta MA, Valentini V, Paiar F, Ramella S, Di Muzio NG, Livi L, Jereczek-Fossa BA, Osti MF, Scorsetti M, Alongi F. A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study. Radiother Oncol. 2022 Jan;166:92-99. doi: 10.1016/j.radonc.2021.10.023. Epub 2021 Nov 5.
- Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, Mulroy L, Lock M, Rodrigues GB, Yaremko BP, Schellenberg D, Ahmad B, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Schlijper R, Bauman GS, Laba J, Qu XM, Warner A, Senan S. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 2020 Sep 1;38(25):2830-2838. doi: 10.1200/JCO.20.00818. Epub 2020 Jun 2.
- Palma DA, Salama JK, Lo SS, Senan S, Treasure T, Govindan R, Weichselbaum R. The oligometastatic state - separating truth from wishful thinking. Nat Rev Clin Oncol. 2014 Sep;11(9):549-57. doi: 10.1038/nrclinonc.2014.96. Epub 2014 Jun 24.
- Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard P, Goldstraw P, Johnston M, McCormack P, Pass H, Putnam JB Jr; International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg. 1997 Jan;113(1):37-49. doi: 10.1016/s0022-5223(97)70397-0.
- Ritter TA, Matuszak M, Chetty IJ, Mayo CS, Wu J, Iyengar P, Weldon M, Robinson C, Xiao Y, Timmerman RD. Application of Critical Volume-Dose Constraints for Stereotactic Body Radiation Therapy in NRG Radiation Therapy Trials. Int J Radiat Oncol Biol Phys. 2017 May 1;98(1):34-36. doi: 10.1016/j.ijrobp.2017.01.204. No abstract available.
- Treasure T, Farewell V, Macbeth F, Monson K, Williams NR, Brew-Graves C, Lees B, Grigg O, Fallowfield L; PulMiCC Trial Group. Pulmonary Metastasectomy versus Continued Active Monitoring in Colorectal Cancer (PulMiCC): a multicentre randomised clinical trial. Trials. 2019 Dec 12;20(1):718. doi: 10.1186/s13063-019-3837-y.
- van Dorp M, Gonzalez M, Daddi N, Batirel HF, Brunelli A, Schreurs WH. Metastasectomy for colorectal pulmonary metastases: a survey among members of the European Society of Thoracic Surgeons. Interdiscip Cardiovasc Thorac Surg. 2023 Feb 6;36(2):ivad002. doi: 10.1093/icvts/ivad002.
- ABR 82437