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OMEGA, Local Ablative Therapy in Oligometastatic NSCLC (OMEGA)

Primary Purpose

Carcinoma, Non-Small-Cell Lung

Status

Unknown status

Phase

Phase 3

Locations

Italy

Study Type

Interventional

Intervention

Surgical removal of primary and/or of all oligometastases

Non-surgical LAT

Standard medical therapy

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Azienda Ospedaliera Universitaria IntegrataRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

LAT arm

Control Arm

Arm Description

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

Standard medical treatment Local ablative therapy on the brain will be administered in any case to patients harboring cerebral oligometastases

Outcomes

Primary Outcome Measures

Overall survival

time interval from randomization until death from any cause

Secondary Outcome Measures

Full Information

NCT ID

NCT03827577

First Posted

January 31, 2019

Last Updated

January 13, 2020

Sponsor

Azienda Ospedaliera Universitaria Integrata Verona

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03827577

Brief Title

OMEGA, Local Ablative Therapy in Oligometastatic NSCLC

Acronym

OMEGA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Unknown status

Study Start Date

October 1, 2019 (Actual)

Primary Completion Date

March 2022 (Anticipated)

Study Completion Date

September 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Azienda Ospedaliera Universitaria Integrata Verona

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Non-Small-Cell Lung

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

195 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

LAT arm

Arm Type

Experimental

Arm Description

Arm Title

Control Arm

Arm Type

Active Comparator

Arm Description

Standard medical treatment Local ablative therapy on the brain will be administered in any case to patients harboring cerebral oligometastases

Intervention Type

Procedure

Intervention Name(s)

Surgical removal of primary and/or of all oligometastases

Intervention Description

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).

Intervention Type

Radiation

Intervention Name(s)

Non-surgical LAT

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Standard medical therapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Overall survival

Description

time interval from randomization until death from any cause

Time Frame

from date of randomization until date of death from any cause up to 60 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Maurizio V Infante, MD

Phone

+390458123335

maurizio.infante@aovr.veneto.it

First Name & Middle Initial & Last Name or Official Title & Degree

Sara Pilotto, MD

sara.pilotto@univr.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Maurizio V Infante

Organizational Affiliation

Azienda Ospedaliera Universitaria Integrata Verona

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Michele Milella, PhD

Organizational Affiliation

Azienda Ospedaliera Universitaria Integrata Verona

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Emilio Bria, PhD

Organizational Affiliation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Official's Role

Principal Investigator

Facility Information:

Facility Name

Azienda Ospedaliera Universitaria Integrata

City

Verona

ZIP/Postal Code

37126

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Maurizio V Infante, MD

maurizio.infante@aovr.veneto.it

First Name & Middle Initial & Last Name & Degree

Sara Pilotto, MD

First Name & Middle Initial & Last Name & Degree

Maurizio V Infante, MD

First Name & Middle Initial & Last Name & Degree

Antonio Santo, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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OMEGA, Local Ablative Therapy in Oligometastatic NSCLC

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