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)

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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

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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

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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

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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

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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