Clinical trial NCT03827577: OMEGA, Local Ablative Therapy in Oligometastatic NSCLC
Official title: OMEGA, A Randomized Trial of Local Ablative Therapy Vs. Conventional Treatment in Oligometastatic NSCLC
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Azienda Ospedaliera Universitaria Integrata Verona
Sponsor class: OTHER
Collaborators: name: A.O.U. Città della Salute e della Scienza - Molinette Hospital
name: San Luigi Gonzaga Hospital
name: Regina Elena Cancer Institute
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Azienda Ospedaliera San Camillo Forlanini
name: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: Humanitas Research Hospital IRCCS, Rozzano-Milan
First posted: 2019-02-01
Enrollment: 195
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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.

Primary outcomes:
measure: Overall survival
timeFrame: from date of randomization until date of death from any cause up to 60 months
Secondary outcomes:
Other outcomes:
Locations:
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata
Study officials:
affiliation: Azienda Ospedaliera Universitaria Integrata Verona
name: Maurizio V Infante
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Universitaria Integrata Verona
name: Michele Milella, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Emilio Bria, PhD
role: PRINCIPAL_INVESTIGATOR
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