OMEGA, Local Ablative Therapy in Oligometastatic NSCLC (OMEGA)

January 13, 2020 updated by: Azienda Ospedaliera Universitaria Integrata Verona

OMEGA, A Randomized Trial of Local Ablative Therapy Vs. Conventional Treatment in Oligometastatic NSCLC

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

195

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Verona, Italy, 37126
        • Recruiting
        • Azienda Ospedaliera Universitaria Integrata
        • Contact:
        • Sub-Investigator:
          • Sara Pilotto, MD
        • Principal Investigator:
          • Maurizio V Infante, MD
        • Sub-Investigator:
          • Antonio Santo, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 81 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  • ECOG performance status 0-1 at the time of randomization
  • Pathologically confirmed NSCLC.
  • Staging with whole-body FDG PET scan and brain MRI or CT with IV contrast.
  • Between 1 and 3 metastatic lesions, assessable according to RECIST v1.1 and suitable for LAT prior to trial registration.
  • Primary tumor controlled (metachronous oligometastasis) or resectable/suitable for ablative radiotherapy.
  • Patient is deemed fit to receive at least 3 cycles of platinum-based doublet chemotherapy, cisplatin or carboplatin, according to local guidelines.
  • If pulmonary involvement, it must be bilateral with at least 3 lung lesions, or extrapulmonary metastasis must be present
  • If brain involvement, up to 2 brain metastases, the largest brain lesion < 3cm in maximum diameter at the time of randomization.

Exclusion criteria

  • Any tumor site besides brain metastasis requiring immediate LAT for palliation.
  • Patient has received previous LAT for extra-cerebral metastasis
  • Patient has received previous systemic treatment for his/her NSCLC malignancy and is experiencing disease progression at the time of randomization (except adjuvant chemotherapy and/or radiotherapy more than 6 months earlier)
  • Patient has had palliative radiotherapy to any tumor site prior to registration and/or requires palliative radiotherapy prior to randomization.
  • High clinical suspicion of direct invasion of the wall of any major blood vessel or medulla by the primary tumor or metastasis
  • Brain metastasis within the brainstem, or leptomeningeal disease.
  • Metastasis in sites where normal radiotherapy constraints cannot be met or in a previously irradiated area
  • Malignant pleural or pericardial effusion.
  • Lung tumors with a single additional nodule in the same lobe, same lung or in the contralateral lung, i.e. T3, T4 or M1a lung cancer, in the absence of extrapulmonary involvement.
  • Lung involvement in the form of multiple nonsolid or subsolid nodules, in the absence of extrapulmonary metastasis [18]
  • History of prior malignant tumour likely to interfere with the protocol treatment or comparisons (excluding H&N primary, radically treated, no recurrence over the last 5 years, non-melanoma skin cancer, in situ cervical cancer, DCIS or LCIS of the breast
  • Any relevant co-morbidities that would significantly reduce life expectancy on their own, such as heart failure, advanced COPD, uncontrolled diabetes, end-stage renal disease etc.
  • Women who are pregnant or breast feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LAT arm

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
Procedure: Surgical removal of primary and/or of all oligometastases
Standard lobectomy or segmentectomy if tumor resectable without pneumonectomy (prefer lobectomy if cardiorespiratory function is not or only moderately compromised, prefer segmentectomy if primary tumor less than 2 cm or cardiorespiratory function is more than moderately compromised but still permissive) Mediastinal lymph node dissection (at least 8 lymphnodes from at least 3 stations including station 7).
Radiation: Non-surgical LAT
Non-surgical LAT may be carried out either by SABR or SBRT or RFA according to site of metastasis, local expertise and availability of resources.
Drug: Standard medical therapy
platinum-based doublet according to local protocols or targeted agents according to EGFR/ALK/ROS-1 mutational status or immunotherapy agents according to PDL1 expression.
Active Comparator: Control Arm

Standard medical treatment

Local ablative therapy on the brain will be administered in any case to patients harboring cerebral oligometastases
Drug: Standard medical therapy
platinum-based doublet according to local protocols or targeted agents according to EGFR/ALK/ROS-1 mutational status or immunotherapy agents according to PDL1 expression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: from date of randomization until date of death from any cause up to 60 months
time interval from randomization until death from any cause
from date of randomization until date of death from any cause up to 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliera Universitaria Integrata Verona

Collaborators

Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
San Luigi Gonzaga Hospital
Azienda Ospedaliera San Camillo Forlanini
Regina Elena Cancer Institute
A.O.U. Città della Salute e della Scienza - Molinette Hospital
Humanitas Research Hospital Milan

Investigators

  • Principal Investigator: Maurizio V Infante, Azienda Ospedaliera Universitaria Integrata Verona
  • Principal Investigator: Michele Milella, PhD, Azienda Ospedaliera Universitaria Integrata Verona
  • Principal Investigator: Emilio Bria, PhD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2019

Primary Completion (Anticipated)

March 1, 2022

Study Completion (Anticipated)

September 1, 2022

Study Registration Dates

First Submitted

January 31, 2019

First Submitted That Met QC Criteria

January 31, 2019

First Posted (Actual)

February 1, 2019

Study Record Updates

Last Update Posted (Actual)

January 18, 2020

Last Update Submitted That Met QC Criteria

January 13, 2020

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1533CESC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe