Colorectal Pulmonary Metastases: Pulmonary Metastasectomy Versus Stereotactic Ablative Radiotherapy

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Процедура Minimally invasive pulmonary metastasectomy
  Surgical margin is equal to tumor size, if possible The goal is a parenchymal-sparing resection
• Лучевая терапия Stereotactic ablative radiotherapy
  Depending on tumor location, 54 Gy in 3 fractions, 55 Gy in 5 fractions, 60 Gy in 8 fractions.

Первичные конечные точки

• Local recurrence-free survival [Срок оценки: From date of randomization through study completion, up to 10 years]

Вторичные конечные точки (10)

• Overall survival (OS) [Срок оценки: 5 years]
• Progression-free survival (PFS) [Срок оценки: 5 years]
• Local recurrence rate (LRR) per tumor [Срок оценки: 5 years]
• Quality of life (QoL) assessment - EuroQoL (EQ-5D-5L) [Срок оценки: 5 years]
• Quality of life assessment - Functional Assessment of Cancer Therapy: General (FACT-G) [Срок оценки: 5 years]
• Health economic evaluation - Institute for Medical Technology Assessment (iMTA) - iMTA Medical Cost Questionnaire (iMCQ) [Срок оценки: 5 years]
• Health economic evaluation - iMTA Productivity Cost Questionnaire (iPCQ) [Срок оценки: 5 years]
• Tumor patterns of failure [Срок оценки: 5 years]
• Rate of adverse events [Срок оценки: 2 years]
• Multiparameter flow cytometric analyses (FACS) [Срок оценки: 1 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Amsterdam University Medical Center (AUMC) — Amsterdam

Публикации

• 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. PMID 7799047
• 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. PMID 9011700
• 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. PMID 24958182
• 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. PMID 28587050
• 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. PMID 23900659
• 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 Tria PMID 32484754
• 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. PMID 31831062
• 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. PMID 28576747

Идентификаторы

NCT: NCT05808790 · ABR 82437

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗