Patient case: 64-year-old female with Lung adenocarcinoma. Genetic variant: ALK Fusion. Other conditions: Emphysema.

Clinical trial: Stereotactic Ablative Radiotherapy for Oligometastatic Non-small Cell Lung Cancer

Summary: The trial will assess the addition of stereotactic ablative radiotherapy (SABR) to standard chemotherapy in patients with oligometastatic non-small cell lung cancer. Patients will be randomised to receive either standard treatment alone (platinum-based doublet chemotherapy) or standard treatment with conventional radiotherapy (RT) and SABR.

Detailed description: SARON is a confirmatory phase III study examining the efficacy and safety of stereotactic ablative radiotherapy (SABR) and conventional radiotherapy (RT) alongside standard chemotherapy in patients with oligometastatic non-small cell lung cancer.
  Current treatment for this group of patients is platinum-based doublet chemotherapy alone. There is sufficient evidence regarding the safety of SABR, its effect on local control and a possible impact on overall survival. This trial will further examine overall survival, progression free survival and local control, as well as toxicity, feasibility, patient reported outcomes and health resource use.
  There will be a feasibility analysis performed after 50 patients have been randomised. This will assess the practicality of achieving recruitment targets, logistics of delivering the experimental treatment and the potential for contamination (as patients may seek SABR outside of the trial if randomised to the non SABR arm). There will also be a parallel thoracic SABR safety and feasibility study after recruitment and treatment of 20 patients with thoracic metastases.
  This is a multicentre randomised phase III study based on patients with oligometastatic NSCLC.
  Trial arms:
  Control Arm: standard treatment alone (platinum-based doublet chemotherapy) Experimental Arm: standard treatment plus radical RT to primary and SABR and/or SRS to metastases

Eligibility: Inclusion criteria
  1. Histologically or cytologically confirmed NSCLC.
  2. Negative or unknown EGFR and ALK mutation (EGFR testing is mandatory and ALK testing to be performed if part of local policy).
  3. Staging with FDG PET-CT whole body scan and MRI brain or CT brain with IV contrast.
  4. Patient presenting with synchronous primary disease and oligometastatic disease.
  5. Patient is deemed fit to receive at least four cycles of platinum-based doublet chemotherapy, cisplatin or carboplatin, according to local guidelines and assessment.
  6. Patient is deemed fit to receive conventional RT and SABR/SRS according to local guidelines and assessment.
  7. Primary tumour suitable for radical RT (either conventional RT or SABR/SRS).
  8. Between one and three metastatic lesions, assessable according to RECIST v1.1 and suitable for SABR/SRS (only one site of metastases or primary tumour needs to be measurable according to RECIST v1.1). Note: If brain metastasis present, the largest lesion must be less than no more than 3cm in maximum diameter at the time of randomisation. The second lesion must be no more than 2cm.
  9. Acceptable lung function for radical lung radiotherapy.
  10. No relevant co-morbidities, including pulmonary fibrosis and connective tissue disorders.
  11. ECOG performance status 0 to 1 at time of registration (can be ECOG 0-2 at randomisation).
  Exclusion criteria
  1. Patient has had palliative radiotherapy to any tumour site prior to registration and/or requires palliative radiotherapy prior to randomisation.
  2. Patient has received any previous treatment for this NSCLC malignancy.
  3. Patients who present with brain metastasis only and no sites of extra cranial metastatic disease i.e. the presence of more than 2 brain metastases is an exclusion criteria.
  4. Brain metastasis within the brainstem.
  5. Metastasis in sites where normal radiotherapy constraints cannot be met.
  6. Metastasis in a previously irradiated area
  7. Patients who had more than three sites of disease prior to trial registration.
  8. Primary tumour or metastases causing direct invasion or high clinical suspicion of direct invasion of the wall of any major blood vessel.
  9. Malignant pleural or pericardial effusion.
  10. Patients with bilateral adrenal metastases.
  11. Stage III disease even with extensive nodal disease.
  12. History of prior malignant tumour likely to interfere with the protocol treatment or comparisons, unless the patient has been without evidence of disease for at least 3 years or the tumour was a non-melanoma skin tumour or early cervical cancer.
  13. Leptomeningeal disease.
  14. Women who are pregnant or breast feeding.

Relevance to patient case: not relevant