LAT for Oligoprogressive NSCLC Treated With First-line OSImertinib (LAT-FLOSI)

Local AblativeTherapy for Oligoprogressive Non-Small-Cell Lung Cancer Treated With First-line OSImertinib

To determine whether in patients with EGFR mutated advanced NSCLC and osimertinib as first-line treatment, the (repeated) use of LAT to ≤ 3 OP lesions and continuation of first-line osimertinib, improves the median progression-free survival by more than 3 months (i.e. PFS2-PFS1 = >3 months).

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor
• Intervention / Treatment: Radiation: Local ablative therapy; Procedure: Local ablative therapy

Detailed Description

The (repeated) use of LAT to ≤ 3 OP lesions with continuation of first-line osimertinib, is endorsed by international guidelines (NCCN, ESMO).

In this phase IIb prospective non-randomized observational trial, we want to document the benefit of LAT in this patient cohort.

• Study Type: Observational
• Enrollment (Estimated): 39

Contacts and Locations

• Study Contact: Name: Patrick Berkovic, MD; Phone Number: +32-16-34-51-15; Email: Patrick.berkovic@uzleuven.be
• Study Contact Backup: Name: Els Wauters, MD, PhD; Phone Number: +32 16-34-09-42; Email: els.wauters@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZLeuven
    • Principal Investigator: Patrick Berkovic, MD
    • Sub-Investigator: Maarten Lambrecht, MD, PhD
    • Sub-Investigator: Els Wauters, MD, PhD
    • Sub-Investigator: Christel Oyen, RN
    • Sub-Investigator: Johan Vansteenkiste, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with an EGFR actionable mutation receiving first-line targeted TKI therapy with osimertinib. Confirmed oligoprogressive disease defined as ≤ 3 intra- and extracranial sites of progressive disease

Description

Inclusion Criteria:

1. Male or female, ≥ 18 years of age
2. Established histological diagnosis of advanced NSCLC, not suitable for radical treatment, with an EGFR actionable mutation receiving first-line targeted TKI therapy with osimertinib
3. Initial radiologically confirmed response (at least stable disease) to osimertinib assessed 3 months post commencing osimertinib according to RECIST criteria v1.1.
4. Confirmed OPD defined as ≤ 3 intra- and extracranial sites of progressive disease. OP may be defined as progression of an individual metastasis according to RECIST or on 2 consecutive imaging studies at least 2 months apart with a minimum of 5mm increase in size from baseline or an unambiguous development of a new metastatic lesion with a grand total of 3 lesions. All sites must be visible, imaging defined targets, not previously treated with radiation or radiofrequency and suitable for treatment with LAT as determined by the local multi-disciplinary team (MDT).
5. Adequate baseline organ function to allow LAT to all the OP targets.
6. Predicted life expectancy ≥ 6 months
7. Karnofsky Index ≥ 60% and ECOG 0-2
8. Provision of written informed consent
9. Female participants must be surgically sterile or postmenopausal if SBRT is planned to the abdominal area or must agree to use effective contraception during the period of therapy.

Exclusion Criteria:

1. > 3 sites of progressive disease
2. Oligoprogressive metastases not amenable to LAT
3. Radiotherapy or radiofrequency ablation near the OP lesion prior to the inclusion in the LAT-FLOSI study
4. Co-morbidities considered clinically precluding the safe use of LAT
5. Any psychological, sociological or geographical issue potentially hampering compliance with the study
6. Pregnancy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS 2	Progression Free Survival 2	Time from start of osimertinib until first PD after LAT or death whichever comes first, up to 3 year after LAT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to next line systemic therapy		Time from LAT until initiation of next line systemic therapy or death whichever comes first, up to 3 years after LAT
Patterns of disease progression	Patterns of disease progression after local ablative therapy (LAT) identified on sequential CT scans taken at 3 monthly intervals to document the natual history of the disease after LAT	Time from LAT until disease progression or death whichever comes first, up to 3 years after LAT
Radiotherapy induced toxicity	Acute and late radiotherapy induced toxicities assessed using the CTCAE v4.0. and the RTOG/EORTC late morbidity score. Acute events are defined as ≤ 90 days post SBRT and late events > 90 days.	Change in toxicity measured from baseline up to 3 years after radiotherapy
Quality of life	Quality of life is measured by the EORTC QLQ-LC13 questionnaire comprised both of multi-item and single-item measures of lung cancer-associated symptoms (i.e. coughing, haemoptysis, dyspnoea and pain) and side-effects from conventional chemo- and radiotherapy (i.e. hair loss, neuropathy, sore mouth and dysphagia).	Change in quality of life measured from baseline up to 3 years after radiotherapy

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 30, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 28, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: First line osimertinib; Local ablative therapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: S63270

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No