A Randomized Phase II Study of Stereotactic Ablative Body Radiotherapy for Metastases to the Lung (TROG 13.01 SAFRON II)

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to determine the safety (defined as number of participants experiencing ≥ 5% toxicity at 12 months post treatment) of stereotactic ablative fractionated radiotherapy versus radiosurgery for oligometastatic neoplasia to the lung.

Detailed Description
-----------------
Stereotactic Ablative Body Radiotherapy (SABR) is an exciting novel radiotherapy technique that is delivered over very few sessions. In the case of limited pulmonary 'oligometastases', SABR can result in long-term survival. It is non-invasive and associated with high rates of tumour control and relatively low toxicity. Additionally, the large doses of precision radiotherapy involved may evoke a strong immune response to recognise and attack any remaining tumour cells. In the future, SABR may be an attractive alternative to invasive surgery. There are two SABR techniques emerging in Australia; fractionated and single fraction treatments. We aim to conduct the first clinical trial of SABR in patients with limited pulmonary metastases testing fractionated versus single fraction treatments. The primary aim of this study is to evaluate the toxicity, Quality of Life, clinical efficacy and cost effectiveness of single fraction SABR compared to multi-fraction SABR in patients with oligometastases to the lung. The secondary aim of this study is to assess the immune response evoked by both fractionated and single fraction SABR and its prognostic implications for patient outcomes.

Official Title
-----------------
Stereotactic Ablative Fractionated Radiotherapy Versus Radiosurgery for Oligometastatic Neoplasia to the Lung: A Randomised Phase II Trial

Conditions
-----------------
Cancer, Metastases to the Lung

Intervention / Treatment
-----------------
* Radiation: Multi-fraction SABR
* Radiation: Single Fraction SABR


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A maximum of three metastases to the lung from any non-haematological malignancy Tumour diameter ≤5cm Targets are located away from central structures (defined as 2cm beyond bifurcation of lobar bronchi and central airways). Targets in proximity to chest wall and mediastinum that meet these inclusion criteria are eligible. Patients must be medically inoperable, technically high risk or have declined surgery. Exclusion Criteria: Previous high-dose thoracic radiotherapy. Cytotoxic chemotherapy within 3 weeks of commencement of treatment, or concurrently with treatment. Hormonal manipulation agents are not excluded (e.g. aromatase inhibitors, selective oestrogen receptor modulators, and gonadotrophin releasing hormone receptor modulators) Targeted agents (such as sunitinib and tarceva) within 7 days of commencement of treatment, or concurrently with treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multi-fraction SABR<br>Radiotherapy: 48Gy delivered in 4 fractions, delivered over 2 weeks, with each fraction delivered 48 hours apart. | Radiation: Multi-fraction SABR<br>* Multi-fraction SABR; 48Gy delivered in 4 fractions, delivered over 2 weeks, with each fraction delivered 48 hours apart.<br>|
| Experimental: Single fraction SABR<br>Radiotherapy: 28Gy delivered in 1 fraction | Radiation: Single Fraction SABR<br>* Single fraction SABR; 28Gy delivered in 1 fraction<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | The primary outcome is safety, defined as number of participants experiencing less than or equal to 5% toxicity at 12 months post treatment (toxicity as measured by CTCAE V4). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | To compare quality of life outcomes between techniques assessed using EQ-5DL and MDASI-LC questionnaires. | 24 months | 
| Time to local failure | Local progression free survival assesed by CT scan and clinical assessment | 24 months | 
| Overall survival | Overall survival assesed by clinical assessment | 24 months | 
| Time to distant failure | Time to distant failure assessed by CT scan and clinical assessment | 24 months | 
| Resources use and costs associated with treatment | Resources use and costs associated with treatment assessed by EQ5DL and accessing Medicare data | 24 months | 
| Disease Free Survival | Disease free survival will be measured from the date of randomisation to the date of a local recurrence, regional or distant metastasis, or death from any cause, whichever occurs first. | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SABR, Oligometastatic, Neoplasia, Radiosurgery, Stereotactic Ablative Body Radiotherapy, Metastases to the Lung, Non Haematological