Stereotactic Ablative Radiotherapy in Locally Advanced Non Small Cell Lung Cancer

Locally Advanced Lung Non-Small Cell Carcinoma Clinical Trial

— START-NEW-ERA  

Official title:

STereotactic Ablative RadioTherapy in NEWly Diagnosed and Recurrent Locally Advanced Non-small Cell Lung Canter Patients Unfit for concurrEnt RAdio-chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05291780
• Other study ID #: SABR-LA-NSCLC 810
• Status: Completed
• Phase: N/A
• Start date: December 2015
• Est. completion date: December 2021

Study information

• Verified date: March 2022
• Source: Radiotherapy Oncology Centre "Santa Maria" Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, non-randomized, single arm, single institution phase II trial to evaluate the safety and effectiveness of stereoractic ablative radiotherapy (SABR) in selected unresectable newly diagnosed and recurrent locally advanced (LA) non-small cell lung cancer (NSCLC) patients unfit for concurrent chemo-radiotherapy (ChT-RT). Patients unfit for concurrent ChT-RT but fit for chemotherapy will be enrolled to sequential ChT-SABR; patients unfit for ChT will be enrolled to exclusive SABR.

Description:

Current standard of care for fit patients with unresectable LA-NSCLC is concurrent chemo-radiotherapy (ChT-RT) which consists of 6 weeks of radiation and chemotherapy. Unfortunately many LA NSCLC patients, particularly the elderly, are unfit for concurrent ChT-RT because of their poor performance status and co-morbidities. Sequential ChT-RT and/or exclusive RT are options available for patients not suitable for concomitant approaches. Median progression-free survival among patients receiving concurrent ChT-RT is poor and no more than 15% of cases are alive at 5 years. This study is evaluating SABR in unresectable LA-NSCLC. Hypofractionated regimens of RT have emerged as a possible approach in LA-NSCLC, not only because prolonged treatments may discourage a proportion of elderly patients (20-30%) who are forced to give up treatment due to distance from the Radiotherapy Centre, but also for radiobiological reasons. Recent technological advances in RT, first of all stereotactic body radiotherapy (SBRT), have made hypofractionation widely applicable with the possibility to administer few (5 to 8) fractions of high external beam doses to the tumor, sparing the surrounding healthy tissues by a rapid fall of dose outside the target. LA-NSCLC patients will be discussed at the multidisciplinary lung cancer group and will be judged unfit for surgery and concurrent ChT-RT (e.g. elderly patients and/or large volume of disease and/or cardiovascular comorbidities) but suitable for RT. Neoadjuvant ChT will be evaluated case by case and will be prescribed only in fit patients. Starting from the standard radical conventionally administered dose for LA-NSCLC (equivalent to at least 54-60 Gy in 27-30 fractions), the investigators decided to prescribe an ablative dose of at least 35-40 Gy in 5 fractions. The SABR dose will be increased, case by case, respecting the maximum tolerance dose of healthy structures. The purpose of this study is to explore SABR in the treatment of unresectable LA-NSCLC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• 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 of 0-2
• Histologically or cytologically confirmed non-small cell lung cancer
• LA-NSCLC at the first diagnosis or recurrent LA-NSCLC after previous surgery
• Stage II-III disease as determined by PET/CT and TC/MRI Brain (American Joint Committee on Cancer 7th or 8th Edition)
• oligo-metastatic LA-NSCLC with metastasis suitable to local treatment in the primary and metastatic site
• Participant is not eligible for surgical resection as determined by the multidisciplinary lung cancer group
• Participant is not eligible for concurrent chemotherapy as determined by the multidisciplinary lung cancer group
• Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).

Exclusion Criteria:

• LA-NSCLC patients eligible for surgical resection
• ECOG performance status 3 or more
• Inability to safely treat target lesions
• Pregnant women are excluded from this study because radiation therapy has known potential for teratogenic or abortifacient effects.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Locally Advanced Lung Non-Small Cell Carcinoma

Intervention

Radiation:
• Stereotactic Ablative Radiotherapy in Unresectable Locally Advanced Non-Small Cell Lung Cancer
The prescribed dose of stereotactic ablative radiotherapy (SABR) will be of at least 35-40 Gy in 5 fractions. The dose of SABR will be increased, case by case, respecting the maximum tolerance dose of the healthy structures. Participants will SABR once a day for 5 days, Monday through Friday (around 1 week).

Locations

Country	Name	City	State
Italy	Radiotherapy Oncology Centre "S.Maria" Hospital	Terni	TR

Sponsors (5)

Lead Sponsor	Collaborator
Radiotherapy Oncology Centre "Santa Maria" Hospital	Ernesto Maranzano,MD, Fabio Trippa,MD, Michelina Casale,PhD, Paola Anselmo,MD

Country where clinical trial is conducted

Italy, 

References & Publications (22)

Ahmed N, Hasan S, Schumacher L, Colonias A, Wegner RE. Stereotactic body radiotherapy for central lung tumors: Finding the balance between safety and efficacy in the "no fly" zone. Thorac Cancer. 2018 Oct;9(10):1211-1214. doi: 10.1111/1759-7714.12764. Epu — View Citation

Arcidiacono F, Aristei C, Marchionni A, Italiani M, Fulcheri CPL, Saldi S, Casale M, Ingrosso G, Anselmo P, Maranzano E. Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients. Br J Radiol. 2020 Nov 1;93(1115):20200645. doi: 10 — View Citation

Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. Meta-analysis of concomitant versus sequential ra — View Citation

Belderbos J, Walraven I, van Diessen J, Verheij M, de Ruysscher D. Radiotherapy dose and fractionation for stage III NSCLC. Lancet Oncol. 2015 Apr;16(4):e156-7. doi: 10.1016/S1470-2045(15)70121-X. — View Citation

Bezjak A, Paulus R, Gaspar LE, Timmerman RD, Straube WL, Ryan WF, Garces YI, Pu AT, Singh AK, Videtic GM, McGarry RC, Iyengar P, Pantarotto JR, Urbanic JJ, Sun AY, Daly ME, Grills IS, Sperduto P, Normolle DP, Bradley JD, Choy H. Safety and Efficacy of a F — View Citation

Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus — View Citation

David EA, Daly ME, Li CS, Chiu CL, Cooke DT, Brown LM, Melnikow J, Kelly K, Canter RJ. Increasing Rates of No Treatment in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Propensity-Matched Analysis. J Thorac Oncol. 2017 Mar;12(3):437-445. doi: 10.1 — View Citation

De Ruysscher D, Botterweck A, Dirx M, Pijls-Johannesma M, Wanders R, Hochstenbag M, Dingemans AM, Bootsma G, Geraedts W, Simons J, Pitz C, Lambin P. Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: a prosp — View Citation

Faivre-Finn C, Vicente D, Kurata T, Planchard D, Paz-Ares L, Vansteenkiste JF, Spigel DR, Garassino MC, Reck M, Senan S, Naidoo J, Rimner A, Wu YL, Gray JE, Özgüroglu M, Lee KH, Cho BC, Kato T, de Wit M, Newton M, Wang L, Thiyagarajah P, Antonia SJ. Four- — View Citation

Fowler JF, Chappell R. Non-small cell lung tumors repopulate rapidly during radiation therapy. Int J Radiat Oncol Biol Phys. 2000 Jan 15;46(2):516-7. — View Citation

Franks KN, Jain P, Snee MP. Stereotactic ablative body radiotherapy for lung cancer. Clin Oncol (R Coll Radiol). 2015 May;27(5):280-9. doi: 10.1016/j.clon.2015.01.006. Epub 2015 Mar 4. — View Citation

Karam SD, Horne ZD, Hong RL, McRae D, Duhamel D, Nasr NM. Hypofractionated stereotactic body radiation therapy for elderly patients with stage IIB-IV nonsmall cell lung cancer who are ineligible for or refuse other treatment modalities. Lung Cancer (Auckl — View Citation

Kaster TS, Yaremko B, Palma DA, Rodrigues GB. Radical-intent hypofractionated radiotherapy for locally advanced non-small-cell lung cancer: a systematic review of the literature. Clin Lung Cancer. 2015 Mar;16(2):71-9. doi: 10.1016/j.cllc.2014.08.002. Epub — View Citation

Kong C, Zhu X, Shi M, Wang L, Chen C, Tao H, Jiang N, Yan P, Zhao L, Song X, He X. Survival and Toxicity of Hypofractionated Intensity Modulated Radiation Therapy in 4 Gy Fractions for Unresectable Stage III Non-Small Cell Lung Cancer. Int J Radiat Oncol — View Citation

Nguyen KNB, Hause DJ, Novak J, Monjazeb AM, Daly ME. Tumor Control and Toxicity after SBRT for Ultracentral, Central, and Paramediastinal Lung Tumors. Pract Radiat Oncol. 2019 Mar;9(2):e196-e202. doi: 10.1016/j.prro.2018.11.005. Epub 2018 Nov 26. — View Citation

Nguyen NP, Bishop M, Borok TJ, Welsh J, Hamilton R, Cohen D, Nguyen LM, Vincent VH. Pattern of failure following chemoradiation for locally advanced non-small cell lung cancer: potential role for stereotactic body radiotherapy. Anticancer Res. 2010 Mar;30 — View Citation

Rodrigues G, Choy H, Bradley J, Rosenzweig KE, Bogart J, Curran WJ Jr, Gore E, Langer C, Louie AV, Lutz S, Machtay M, Puri V, Werner-Wasik M, Videtic GMM. Definitive radiation therapy in locally advanced non-small cell lung cancer: Executive summary of an — View Citation

Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, Shankar L, Bogaerts J, Chen A, Dancey J, Hayes W, Hodi FS, Hoekstra OS, Huang EP, Lin N, Liu Y, Therasse P, Wolchok JD, Seymour L. RECIST 1.1-Update and clarification: From the RECIST com — View Citation

Sigel K, Lurslurchachai L, Bonomi M, Mhango G, Bergamo C, Kale M, Halm E, Wisnivesky J. Effectiveness of radiation therapy alone for elderly patients with unresected stage III non-small cell lung cancer. Lung Cancer. 2013 Nov;82(2):266-70. doi: 10.1016/j. — View Citation

Tekatli H, Haasbeek N, Dahele M, De Haan P, Verbakel W, Bongers E, Hashemi S, Nossent E, Spoelstra F, de Langen AJ, Slotman B, Senan S. Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with "Ultracentral" Non-Small Cell Lung Cance — View Citation

Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med. 2009 May;50 Suppl 1:122S-50S. doi: 10.2967/jnumed.108.057307. Review. — View Citation

Wang S, Wong ML, Hamilton N, Davoren JB, Jahan TM, Walter LC. Impact of age and comorbidity on non-small-cell lung cancer treatment in older veterans. J Clin Oncol. 2012 May 1;30(13):1447-55. doi: 10.1200/JCO.2011.39.5269. Epub 2012 Mar 26. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local control	A lack of progression (i.e., any response and stable disease) of the treated volume according to RECIST and PERCIST. Local recurrence (LR) was defined as tumor progression within the radiation field (95% of the recurrence volume within the original 80% isodose of SABR). Local recurrence-free survival (LR-FS) was defined as the interval between treatment and radiological evidence of LR.	1 year, 2 years and 3 years
Primary	Proportion of Participants Experiencing Grade 3 or Higher Toxicities	SABR will be considered safe if no grade (G) 3 or higher toxicities appears. Toxicity, graded according to Common Terminology Criteria for Adverse Events (CTCAE v3.0) will be assessed during SABR and at all follow-up intervals. Toxicity will be recorded as acute when occurred during SABR or within 3 months after completion of treatment. When the time interval will be longer than 3 months, toxicity will be defined late.	6 months and 1 year
Secondary	Thoracic nodal-recurrence free survival	The interval between treatment and radiological evidence of any nodal recurrence outside the treated nodes and anyway outside the original isodose of 80%	1 year, 2 years and 3 years
Secondary	Distant progression free-survival	The interval between treatment and radiological evidence of systemic disease progression	1 year, 2 years and 3 years
Secondary	Overall Survival	The overall survival will be calculated from treatment to patient death or last follow-up	1 year, 2 years, 3 years and 5 years