OMEGA, Local Ablative Therapy in Oligometastatic NSCLC

Phase 3

• Conditions: Carcinoma, Non-Small-Cell Lung
• Interventions: Procedure: Surgical removal of primary and/or of all oligometastases; Drug: Standard medical therapy; Radiation: Non-surgical LAT

• Registration Number: NCT03827577
• Lead Sponsor: Azienda Ospedaliera Universitaria Integrata Verona

Brief Summary

Oligometastatic lung cancer (OM-NSCLC) seems to be associated with a better prognosis than usual Stage IV non-small cell lung cancer when radical local therapy of all metastatic sites is administered but the impact of such an approach on overall survival and quality of life remains to be defined by adequately powered phase III trials.

A consortium of tertiary referral centres involved in Lung Cancer management at the national level was established to launch a randomized trial of local ablative therapy in OM-NSCLC patients with potentially resectable or locally controlled primary tumors has been designed.

Inclusion criteria include adequate performance status, primary tumor controlled or controllable staging with whole-body FDG PET scan and brain MRI, fit to receive at least 3 cycles of platinum-based doublet chemotherapy, or immunotherapy or targeted agents according to molecular profile.

Exclusion criteria include cerebral oligometastasis alone (will receive local therapy in any case), metastasis in sites where normal radiotherapy constraints cannot be met, multiple subsolid nodules in the absence of extrapulmonary metastasis, prior malignant tumor with some exceptions, relevant co-morbidities that would significantly reduce life expectancy on their own.

Patients with synchronous or metachronous oligometastatic lung cancer (1-3 metastatic lesions) will be randomized to local ablative therapy + standard treatment Vs. standard treatment. Balancing between study arms will be performed according to synchronous vs. metachronous presentation, Number of oligometastases, Nodal status and Oncogene-addiction or PDL-1 expression. Primary outcome will be Overall Survival (OS) from randomization. The sample size is set to 195 patients.

Disease state and life status will be assessed on a 3-monthly basis by physical examination, whole-body CT scan plus repeat PET-scan if needed and Brain MRI if brain metastasis at enrolment. Toxicity and adverse events will be assessed according to NCI-Common Terminology Criteria. And RTOG criteria. Quality of life will be assessed at randomization and after six months by the SF36/LCSS

Detailed Description

Lung cancer is a systemic disease with local manifestations that are ultimately responsible for a reduced life expectancy in a relatively large subgroup of metastatic lung cancer patients.

In such a subgroup, local ablative therapy of the primary tumor and of all metastatic lesions with a combination of surgery and/or radiotherapy should lead to a clinically significant improvement of their overall survival with acceptable morbidity and preserved Quality of Life compared with medical treatment alone

OMEGA is a randomized trial of local ablative therapy in NSCLC patients with potentially resectable or locally controlled primary tumors and oligometastatic disease

The decision to randomise OM-NSCLC patients either before any systemic therapy or after 3 months of treatment without progression is left to the recruiting centre(s).

Local ablative therapy will be administered in any case to patients harboring cerebral oligometastasis

Statistical methods

Dynamic balancing as per the method of Pocock and Simon \[16\] according to:

* Synchronous vs. metachronous presentation

* Number of oligometastases (1 vs. 2-3) including extrathoracic N3 disease

* Nodal status (N0 vs. N+)

* Oncogene-addiction (EGFR/ALK/ROS-1 driven or PDL1 \>50% vs \<50% vs. wild type)

Study Timeline

• Study First Submitted: 2019-01-31
• Study First Submitted QC: 2019-01-31
• Study First Posted: 2019-02-01
• Status Verified: 2019-10
• Study Start: 2019-10-01
• Last Update Submitted: 2020-01-13
• Last Update Posted: 2020-01-18
• Primary Completion: 2022-03
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 195

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LAT arm	Surgical removal of primary and/or of all oligometastases	Lung resection (if primary in place) + local ablative therapy of all metastatic sites + standard medical treatment. patients may be enrolled either before any systemic therapy or after 3 months of treatment without progression according to local coordinator decision
Control Arm	Standard medical therapy	Standard medical treatment Local ablative therapy on the brain will be administered in any case to patients harboring cerebral oligometastases
LAT arm	Standard medical therapy	Lung resection (if primary in place) + local ablative therapy of all metastatic sites + standard medical treatment. patients may be enrolled either before any systemic therapy or after 3 months of treatment without progression according to local coordinator decision
LAT arm	Non-surgical LAT	Lung resection (if primary in place) + local ablative therapy of all metastatic sites + standard medical treatment. patients may be enrolled either before any systemic therapy or after 3 months of treatment without progression according to local coordinator decision

Primary Outcome Measures

Name	Time	Method
Overall survival	from date of randomization until date of death from any cause up to 60 months	time interval from randomization until death from any cause

Trial Locations

Locations (1)

Azienda Ospedaliera Universitaria Integrata; 🇮🇹 Verona, Italy