Stereotactic Ablative Radiotherapy in Synchronous and Metachronous Oligo-Metastatic Non Small Cell Lung Cancer

Non Small Cell Lung Cancer Clinical Trial

— STARTNEWERA-OM  

Official title:

STereotactic Ablative RadioTherapy in NEWly Synchronous and mEtachRonous (Oligo-persistence, Oligo-induced, Oligo-progression) Oncogene and Non Oncogene Addicted OLIGO-metastatic Non-small Cell Lung Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06207292
• Other study ID #: SABR-oligoM NSCLC 810
• Status: Recruiting
• Phase: N/A
• Start date: December 2016
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Radiotherapy Oncology Centre "Santa Maria" Hospital
• Contact: Fabio Arcidiacono, MD
• Phone: +390744205729
• Email: f.arcidiacono[@]aospterni.it
• 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 stereotactic ablative radiotherapy (SABR) in oncogene addicted and non-oncogene addicted synchronous and/or metachronous oligo-metastatic (oligoM) non-small cell lung cancer (NSCLC) patients.

Description:

Targeted Therapies and Immunotherapy have fundamentally changed the treatment of metastatic non-small cell lung cancer (NSCLC).

There is an increasing interest in the use of stereotactic ablative radiotherapy (SABR) for oligo-metastatic (oligo-M) NSCLC patients. It is postulated that definitive treatment of the primary as well as regional node/s and oligo-M in these patients may improve their overall survival (OS). Oligo-M is considered an intermediate state between local and poly-metastatic disease and is commonly defined as 1-5 metastatic lesions, in keeping with the recent European Society of Radiotherapy and Oncology (ESTRO) and American Society for Radiation Oncology (ASTRO) consensus.

If discovered within 4-6months of diagnosis, they are termed synchronous oligo-M. Alternatively, should oligo-M develop following definitive treatment of the primary tumour, this is termed metachronous oligo-M.

Multiple clinical trials have demonstrated prolonged survival following SABR treatment to all sites of oligo-M, particularly in NSCLC.

Targeted therapies (TT) and Immunotherapy (IT) have transformed the landscape of NSCLC treatment by improving OS in metastatic setting. However, most SABR trials for oligo-M patients were conducted in the pre-TT and pre-IT era. How SABR and TT or IT should be integrated in the treatment of oligo-M NSCLC therefore remains an active area of investigation.

Oligo-M is considered a clinically distinct from poly-metastatic disease, presenting a unique therapeutic window during which the treatment of all oligo-M may result in long-term disease control and possibly cure in select cases.

SABR offers the advantages of being non-invasive, safe, and well-tolerated, even by frail patients. It ablates multiple targets simultaneously achieving good rates of local control. The objectives of treating oligo-M using SABR include:

1. ablating all sites of visible disease to reduce tumor burden

2. preventing progression to a poly-metastatic disease state

3. relieving morbidity associated with metastases without a decline in quality of life (QoL)

4. delaying the start of systemic therapy

Reasons to support SABR in oligo-M NSCLC:

1. Systemic treatment alone does not eradicate the presence of all oligo-M disease. SABR may improve local control at the sites of oligo-M decreasing the risk of poly-metastatic widespread by reducing the burden of proliferative malignant cells

2. SABR is a histology-agnostic ablative technique which can eradicate systemic therapy-resistant disease. So, SABR optimizes local control at the sites of oligo-M, thereby delaying the need to start a new systemic therapy or eliminating the morbidity and potential mortality associated with local and eventually distant progression of disease.

• Targeted therapies (TT) or Immunotherapy (IT) (chemotherapy) will be combined with early SABR of all cancer sites in patients with synchronous oligo-M NSCLC: primary tumour (T), regional node/s (N) and oligo-metastases (M). Eradication of all macroscopic cancer sites at the time of primary diagnosis by combined modality treatment is expected to decrease the risk of resistance development with only microscopic disease potentially remaining. This will result in improvement of progression free survival (PFS), QoL, delayed change of therapy and OS without added high-grade (>G3) toxicity. Synchronous oligo-M NSCLC patients will be enrolled to SABR and TT or IT.

• Targeted therapies or Immunotherapy (chemotherapy) will be combined with SABR of all cancer residual sites in patients with oligo-persistence, oligo-progressive or oligo- induced oligo-M NSCLC: primary tumour (T), regional node/s (N) and oligo-M. Eradication of all macroscopic cancer sites at the time of oligo-persistence or oligo- progression by combined modality treatment is expected to delay the initiation of a new systemic therapy. This will result in improvement of PFS and QoL, delayed change of therapy and OS without added high-grade (>G3) toxicity. Metachronous oligo-M NSCLC patients will be enrolled to SABR including maintenance TT or IT.

• Patients unfit for systemic therapy with synchronous or metachronous oligo-M NSCLC will be enrolled to receive SABR alone in all sites of disease. Eradication of all macroscopic cancer sites is expected to delay the widespread and/or symptomatic disease. This will result in improvement of OS and QoL without added high-grade (>G3) toxicity.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

• histologically confirmed NSCLC

• synchronous oligo-M NSCLC as determined by Positron emission tomography- computed tomography (PET/CT) and brain MRI (AJCC 8th edition)

• metachronous oligo-M NSCLC (oligo-persistence, oligo-progressive, oligo-induced) as determined by PET/CT and brain magnetic resonance imaging (MRI) (AJCC 8th edition)

• patients with at least one target to be treated by SABR at the body

• patients with brain metastases synchronous to the body will be enrolled only if amenable to radiosurgery (the number of brain metastases does not enter into the count of the number of oligo-M)

• patients with a previous history of brain metastases will be enrolled only if the previously treated brain metastases are in control

Exclusion Criteria:

• Ability to understand and the willingness to sign an institutional review board (IRB)- approved informed consent document (either directly or via a legally authorized representative)

• 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
• EGF-R Positive Non-Small Cell Lung Cancer
• Lung Neoplasms
• Neoplasm Metastasis
• Non Small Cell Lung Cancer
• Non Small Cell Lung Cancer Metastatic
• Non-Small Cell Adenocarcinoma
• Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor
• NSCLC
• NSCLC Stage IV
• NSCLC Stage IV Without EGFR/ALK Mutation
• Oligometastatic Disease

Intervention

Radiation:
• Stereotactic Ablative Radiotherapy
The prescribed dose of stereotactic ablative radiotherapy (SABR) will be chosen based on the target to be treated and its proximity to organs at risk(s): Lung-peripheral 33-45 Gy/ 3 fractions Lung-central/ultra-central 35-60 Gy/5 fractions Mediastinal/supraclavicular node 35-45 Gy/5 fractions Liver 45-54 Gy/3 fractions; 50-65 Gy/5 fractions Bone non-spine 30-36 Gy/3 fractions; 35-50 Gy/5 fractions Bone spine 30-33 Gy/3 fractions (SIB); 35-40 Gy/ 5 fractions (SIB) Abdominal-pelvic node 33-39 Gy/ 3 fractions; 35-50 Gy/5 fractions Adrenal gland 30-42 Gy/3 fractions; 35-50 Gy/5 fractions

Locations

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

Sponsors (4)

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

Country where clinical trial is conducted

Italy, 

References & Publications (17)

Arcidiacono F, Anselmo P, Casale M, Zannori C, Ragusa M, Mancioli F, Marchetti G, Loreti F, Italiani M, Bracarda S, Maranzano E, Trippa F. STereotactic Ablative RadioTherapy in NEWly Diagnosed and Recurrent Locally Advanced Non-Small Cell Lung Cancer Pati — 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

Bahig H, Tonneau M, Blais N, Wong P, Filion E, Campeau MP, Vu T, Al-Saleh A, Tehfe M, Florescu M, Roberge D, Masucci L, Richard C, Menard C, Routy B. Stereotactic Ablative Radiotherapy for oligo-progressive disease refractory to systemic therapy in Non-Sm — View Citation

Baydoun A, Lee VL, Biswas T. Oligometastatic Non-Small Cell Lung Cancer: A Practical Review of Prospective Trials. Cancers (Basel). 2022 Oct 29;14(21):5339. doi: 10.3390/cancers14215339. — View Citation

Correa RJ, Salama JK, Milano MT, Palma DA. Stereotactic Body Radiotherapy for Oligometastasis: Opportunities for Biology to Guide Clinical Management. Cancer J. 2016 Jul-Aug;22(4):247-56. doi: 10.1097/PPO.0000000000000202. — View Citation

Gomez DR, Tang C, Zhang J, Blumenschein GR Jr, Hernandez M, Lee JJ, Ye R, Palma DA, Louie AV, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Welsh JW, Gibbons DL, Karam JA, Kavanagh BD, Tsao AS, Sepesi B, Swisher SG, Heymach JV. Local Consolidative Thera — View Citation

Guckenberger M, Lievens Y, Bouma AB, Collette L, Dekker A, deSouza NM, Dingemans AC, Fournier B, Hurkmans C, Lecouvet FE, Meattini I, Mendez Romero A, Ricardi U, Russell NS, Schanne DH, Scorsetti M, Tombal B, Verellen D, Verfaillie C, Ost P. Characterisat — View Citation

Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, Dowell JE, Cheedella N, Nedzi L, Westover KD, Pulipparacharuvil S, Choy H, Timmerman RD. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinica — View Citation

Jongbloed M, Bartolomeo V, Steens M, Dursun S, van de Lisdonk T, De Ruysscher DKM, Hendriks LEL. Treatment outcome of patients with synchronous oligometastatic non-small cell lung cancer in the immunotherapy era: Analysis of a real-life intention-to-treat — View Citation

Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I, Mendez Romero A, Nevens D, Palma D, Park C, Ricardi U, Scorsetti M, Yu J, Woodward WA. Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus docum — 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, Griffioen G, Senthi S, Swaminath A, Kopek N, Liu M, Moore K, Currie S, Bauman GS, Warner A, Senan S. Stereotactic ablative rad — 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. Stereotact — View Citation

Peng P, Gong J, Zhang Y, Zhou S, Li Y, Han G, Meng R, Chen Y, Yang M, Shen Q, Chu Q, Xia S, Zhang P, Zhang L, Chen Y, Zhang L. EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multic — View Citation

Remon J, Menis J, Levy A, De Ruysscher DKM, Hendriks LEL. How to optimize the incorporation of immunotherapy in trials for oligometastatic non-small cell lung cancer: a narrative review. Transl Lung Cancer Res. 2021 Jul;10(7):3486-3502. doi: 10.21037/tlcr — 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(Suppl 1):122S-50S. doi: 10.2967/jnumed.108.057307. — View Citation

Wang XS, Bai YF, Verma V, Yu RL, Tian W, Ao R, Deng Y, Zhu XQ, Liu H, Pan HX, Yang L, Bai HS, Luo X, Guo Y, Zhou MX, Sun YM, Zhang ZC, Li SM, Cheng X, Tan BX, Han LF, Liu YY, Zhang K, Zeng FX, Jia L, Hao XB, Wang YY, Feng G, Xie K, Lu Y, Zeng M. Randomize — View Citation

Zayed S, Louie AV, Breadner DA, Palma DA, Correa RJM. Radiation and immune checkpoint inhibitors in the treatment of oligometastatic non-small-cell lung cancer: a practical review of rationale, recent data, and research questions. Ther Adv Med Oncol. 2023 — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	new systemic therapy-free survival	time that the patient maintains the same therapy without the need to change it	6 months; 1 year, 2 years, 3 years and 5 years
Primary	systemic therapy-free survival	time in which the patient does not need to start systemic therapy (for patients without active systemic therapy)	6 months; 1 year, 2 years, 3 years and 5 years
Primary	proportion of patients experiencing grade 3 or higher toxicities	SABR will be considered safe if no grade (G) or higher toxicities appears. Toxicity will be evaluated according CTCAE scale	6 months; 1 year, 2 years, 3 years and 5 years
Secondary	progression free survival	The interval between treatment and radiological evidence of any progression	6 months; 1 year, 2 years, 3 years and 5 years
Secondary	overall survival	The interval between treatment and death	6 months; 1 year, 2 years, 3 years and 5 years
Secondary	local control	A lack of progression (i.e. any response and stable disease) of the treated volume	6 months; 1 year, 2 years, 3 years and 5 years
Secondary	time to new oligo-metastatic evidence	The interval between treatment and radiological evidence of new oligo-metastatic progression amenable by SABR	6 months; 1 year, 2 years, 3 years and 5 years
Secondary	time to time to poly-metastatic progression not amenable by SABR	The interval between treatment and radiological evidence of poly-metastatic progression not amenable by SABR	6 months; 1 year, 2 years, 3 years and 5 years