Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy

Colorectal Cancer Metastatic Clinical Trial

— COPPER  

Official title:

Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy: a Phase III Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05808790
• Other study ID #: ABR 82437
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2024
• Est. completion date: December 31, 2030

Study information

• Verified date: April 2023
• Source: Amsterdam UMC, location VUmc
• Contact: Martijn van Dorp, MD
• Phone: +31 20 444 4444
• Email: m.vandorp[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 394
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Lung Metastases
• Neoplasm Metastasis
• Neoplasms, Second Primary

Intervention

Procedure:
• Minimally invasive pulmonary metastasectomy
Surgical margin is equal to tumor size, if possible The goal is a parenchymal-sparing resection

Radiation:
• Stereotactic ablative radiotherapy
Depending on tumor location, 54 Gy in 3 fractions, 55 Gy in 5 fractions, 60 Gy in 8 fractions.

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Center (AUMC)	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc	Dutch Cancer Society

Country where clinical trial is conducted

Netherlands, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local recurrence-free survival	Time from randomization to local recurrence or death from any cause	From date of randomization through study completion, up to 10 years
Secondary	Overall survival (OS)	Time from randomization to death from any cause	5 years
Secondary	Progression-free survival (PFS)	Time from randomization to disease progression at any site or death	5 years
Secondary	Local recurrence rate (LRR) per tumor	Proportion of treated metastases with local recurrence	5 years
Secondary	Quality of life (QoL) assessment - EuroQoL (EQ-5D-5L)	[0-5 for 5 dimensions, higher score = worse QoL]	5 years
Secondary	Quality of life assessment - Functional Assessment of Cancer Therapy: General (FACT-G)	[27 questions in 4 subscales, higher score = better QoL]	5 years
Secondary	Health economic evaluation - Institute for Medical Technology Assessment (iMTA) - iMTA Medical Cost Questionnaire (iMCQ)	Medical costs [Euro]	5 years
Secondary	Health economic evaluation - iMTA Productivity Cost Questionnaire (iPCQ)	Productivity costs [Euro]	5 years
Secondary	Tumor patterns of failure	Local, regional and distant disease control based on surveillance imaging	5 years
Secondary	Rate of adverse events	Frequency of adverse events and serious adverse events	2 years
Secondary	Multiparameter flow cytometric analyses (FACS)	Peripheral blood mononuclear cell (PBMC) concentration	1 months