Consolidation Conventional Radiotherapy + Stereotactic Body Radiotherapy at 3 Months After First-line Chemotherapy in Stage IV Oligometastatic Non-small Cell Lung Cancer

Non-small Cell Lung Cancer Clinical Trial

Official title:

Consolidation Conventional Radiotherapy + Stereotactic Body Radiotherapy of All Body Locations With the Disease at 3 Months After First Line Chemotherapy in Stage IV Oligometastatic Non-small Cell Lung Cancer, Prior to Maintenance Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04758481
• Other study ID #: RVO-FNOs/2020-22
• Status: Recruiting
• Phase: N/A
• Start date: May 4, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: December 2022
• Source: University Hospital Ostrava
• Contact: Jirí Hyncica
• Phone: 0042059737
• Email: jiri.hyncica[@]fno.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lung cancer is the main cause of death among cancer diseases, in the Czech Republic, as well as worldwide. Non-small cell lung cancer (NSCLC) is responsible for more than 80% of deaths among cancer patients. Bronchogenic carcinoma is the reason of death of almost 5.500 cases every year in the Czech Republic, the mortality/incidence ration varies around 85%. The main cause for these unfavorable findings is the late detection of the carcinoma in late stages only (III and IV), when a long-term control of the disease is exceptional. Chemotherapy is able to prolong the life of patients with NSCLC by less than one year on average, that is why new treatment approaches are being examined.

Description:

The basic treatment modality of lung cancer is radiotherapy, which has a proven therapeutic benefit in radical and palliative indications in up to 76% of all patients. Stereotactic robotic radiotherapy reaches maximum precision due to the precise definition of the target volume. In some localities, management with images has been solved using modern software instruments, which are able to visualize the tumor and monitor it during the whole course of respiratory cycle. This is directly associated with minimizing radiation of healthy tissues, especially the healthy lung parenchyma. In order to define predictive factors of survival of cancer patients, it is necessary to use molecular markers.

The aim of the study is to verify the feasibility of consolidation SBRT (Stereotactic Body RadioTherapy) - CyberKnife, with subsequent maintenance chemotherapy in patients with stage IV NSCLC, with max. 10 metastatic nidi. The main focus of the study will be on assessment of combination treatment toxicity.

The project is a phase I/II non-randomized clinical trial. Patients with stage IV NSCLC will be treated with 2-4 cycles of chemotherapy - platinum doublet (cisplatinum - cDDP/carboplatinum - CBDCA + Pemetrexed/navelibne - NVB). In cases when disease stabilization (SD)/partial resection (PR) will be achieved, based upon restaging examinations (CT), radiotherapy (RT) of the primary tumour will follow, with lymphadenopathy and SBRT of all metastatic nidi (max. 10 intra- or extracranial metastases). Standard fractionation schemes for RT and SBRT will be used (RT 40-50 Gy/16-20 fractions, SBRT 30 Gy/1 fractionation, 50-60 Gy/3-5 fractionations). At 3-6 weeks after the end of RT, maintenance treatment will be initiated in all patients treated with Peterexed. Regular restaging examinations are planned every 3 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with previously untreated, non-resectable, stage IV NSCLC verified with histology or cytology (according to American Joint Committee on Cancer Version 8).

• Patients must undergo 2-4 cycles of first-line chemotherapy, with the effect of disease stabilization or partial response.

• Patients over 18 years of age.

• Patients with measureable disease (on CT, PET/CT, MRI).

• Patients with 3-10 extracranial/intracranial lesions confirmed on CT, PET/CT, MRI, max. 4 weeks prior to start of SBRT.

• Max. 10 irradiated volumes (primary tumour + lymphadenopathy in one volume, if technically feasible).

• Performance status (PS) 0-2 according to ECOG. Assessment of PS max. 7 days prior to start of treatment.

• AST, ALT & ALP = 2.5x norm. Total bilirubin must be within the normal range. 9. Normal function of bone marrow - Adiponectin = 1.5, Haemoglobin = 100, thrombo = 100.

• Serum creatinine =1.5x norm.

• The entry laboratory tests must not be older than 14 days prior to start of treatment.

• Negative pregnancy test and use of contraception in women of childbearing age.

• Patients undergoing SBRT for pulmonary nidi must undergo entry spirometry with the value FEV1 (forced expiratory volume in 1 second) = 1L.

• Patients must sign informed consent.

Exclusion Criteria:

• Patients with small-cell lung cancer or with mixed aetiology with SCLC.

• Serious ongoing infections.

• Patients with a history of haematopoiesis disorders.

• Weight loss exceeding 10% within the last 3 months.

• Patients with skin metastases of NSCLC.

• Patients treated for other malignity within the last 5 years

• Patients with more than 10 extracranial/intracranial metastases.

• Malignant fluidothorax > 1 cm prior to start of treatment.

• Patients treated with targeted treatment for EGFR mutation or EML-4-ALK translocation in the 1st-line (Erlotinib, Gefitinib, Afatinib, Crizotinib, …).

• Patients treated with immunotherapy (anti-PD-1, anti-PD-L1 or anti-PD-L2, anti CTLA-4, …).

• Participation in another clinical trial within the last month before the start of NSCLC treatment.

• Inability to cooperate or comply with the study protocol.

• Decision of the patient to discontinue participation in the study.

• Pregnant women.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Radiation:
• primary tumour radiotherapy
The study subjects will undergo primary tumour radiotherapy.
• stereotactic body radiotherapy
The study subjects will undergo stereotactic body radiotherapy.
• maintenance radiotherapy
The study subjects will undergo maintenance radiotherapy.

Locations

Country	Name	City	State
Czechia	University Hospital Ostrava	Ostrava	Moravian-Silesian Region

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Ostrava

Country where clinical trial is conducted

Czechia, 

References & Publications (10)

Collen C, Christian N, Schallier D, Meysman M, Duchateau M, Storme G, De Ridder M. Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients. Ann Oncol. 2014 Oct;25(10):1954-1959. doi: 10.1093/annonc/mdu370. Epub 2014 Aug 11. — View Citation

Guerrero E, Ahmed M. The role of stereotactic ablative radiotherapy (SBRT) in the management of oligometastatic non small cell lung cancer. Lung Cancer. 2016 Feb;92:22-8. doi: 10.1016/j.lungcan.2015.11.015. Epub 2015 Dec 2. — View Citation

Lussier YA, Xing HR, Salama JK, Khodarev NN, Huang Y, Zhang Q, Khan SA, Yang X, Hasselle MD, Darga TE, Malik R, Fan H, Perakis S, Filippo M, Corbin K, Lee Y, Posner MC, Chmura SJ, Hellman S, Weichselbaum RR. MicroRNA expression characterizes oligometastasis(es). PLoS One. 2011;6(12):e28650. doi: 10.1371/journal.pone.0028650. Epub 2011 Dec 13. — View Citation

Norihisa Y, Nagata Y, Takayama K, Matsuo Y, Sakamoto T, Sakamoto M, Mizowaki T, Yano S, Hiraoka M. Stereotactic body radiotherapy for oligometastatic lung tumors. Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):398-403. doi: 10.1016/j.ijrobp.2008.01.002. Epub 2008 Apr 18. — View Citation

Oh D, Ahn YC, Seo JM, Shin EH, Park HC, Lim DH, Pyo H. Potentially curative stereotactic body radiation therapy (SBRT) for single or oligometastasis to the lung. Acta Oncol. 2012 May;51(5):596-602. doi: 10.3109/0284186X.2012.681698. Epub 2012 May 1. — View Citation

Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M, Gomi K, Karasawa K, Hayakawa K, Niibe Y, Takai Y, Kimura T, Takeda A, Ouchi A, Hareyama M, Kokubo M, Kozuka T, Arimoto T, Hara R, Itami J, Araki T. Stereotactic body radiotherapy (SBRT) for operable stage I non-small-cell lung cancer: can SBRT be comparable to surgery? Int J Radiat Oncol Biol Phys. 2011 Dec 1;81(5):1352-8. doi: 10.1016/j.ijrobp.2009.07.1751. Epub 2010 Jul 16. — View Citation

Singh D, Chen Y, Hare MZ, Usuki KY, Zhang H, Lundquist T, Joyce N, Schell MC, Milano MT. Local control rates with five-fraction stereotactic body radiotherapy for oligometastatic cancer to the lung. J Thorac Dis. 2014 Apr;6(4):369-74. doi: 10.3978/j.issn.2072-1439.2013.12.03. — View Citation

Siva S, MacManus M, Ball D. Stereotactic radiotherapy for pulmonary oligometastases: a systematic review. J Thorac Oncol. 2010 Jul;5(7):1091-9. doi: 10.1097/JTO.0b013e3181de7143. — View Citation

Takeda A, Kunieda E, Ohashi T, Aoki Y, Koike N, Takeda T. Stereotactic body radiotherapy (SBRT) for oligometastatic lung tumors from colorectal cancer and other primary cancers in comparison with primary lung cancer. Radiother Oncol. 2011 Nov;101(2):255-9. doi: 10.1016/j.radonc.2011.05.033. — View Citation

Wong AC, Watson SP, Pitroda SP, Son CH, Das LC, Stack ME, Uppal A, Oshima G, Khodarev NN, Salama JK, Weichselbaum RR, Chmura SJ. Clinical and molecular markers of long-term survival after oligometastasis-directed stereotactic body radiotherapy (SBRT). Cancer. 2016 Jul 15;122(14):2242-50. doi: 10.1002/cncr.30058. Epub 2016 May 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute and late toxicity	Acute and late toxicity of the combination therapy will be observed (according to Common Terminology for Clinical Adverse Event (CTCAE, version 5)	every 3 months, throughout the study duration, up to 32 months in total
Primary	Progression-free survival	Progression-free survival will be observed	every 3 months
Secondary	Overall survival	Overall survival will be observed	every 3 months, throughout the study duration, up to 32 months in total
Secondary	Share of nidi under local control	The share of nidi under local control will be observed (in per cent/total number of nidi)	every 3 months, throughout the study duration, up to 32 months in total
Secondary	Time to new nidus formation	The time to new nidus formation will be observed	every 3 months, throughout the study duration, up to 32 months in total
Secondary	Duration of maintenance chemotherapy	The duration of maintenance chemotherapy will be observed.	every 3 months, throughout the study duration, up to 32 months in total