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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Metastases to the Lung
• Intervention / Treatment: Radiation: Multi-fraction SABR; Radiation: Single Fraction SABR

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Newcastle, New South Wales, Australia, 2298
      • Calvary Mater Hospital
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Northern Sydney Cancer Centre (RNS)
    • Sydney, New South Wales, Australia, 2560
      • Cambelltown Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Center
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A maximum of three metastases to the lung from any non-haematological malignancy
2. Tumour diameter ≤5cm
3. 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.
4. Patients must be medically inoperable, technically high risk or have declined surgery.

Exclusion Criteria:

1. Previous high-dose thoracic radiotherapy.
2. 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)
3. Targeted agents (such as sunitinib and tarceva) within 7 days of commencement of treatment, or concurrently with treatment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response	To explore immune system responses to single fraction and multi-fraction SABR.	3 months

Collaborators and Investigators

• Sponsor: Trans Tasman Radiation Oncology Group
• Collaborators: Australasian Lung Cancer Trials Group
• Investigators: Study Chair: Shankar Siva, Peter MacCallum Cancer Centre, Australia

Publications and helpful links

General Publications

• Siva S, Bressel M, Mai T, Le H, Vinod S, de Silva H, Macdonald S, Skala M, Hardcastle N, Rezo A, Pryor D, Gill S, Higgs B, Wagenfuehr K, Montgomery R, Awad R, Chesson B, Eade T, Wong W, Sasso G, De Abreu Lourenco R, Kron T, Ball D, Neeson P; Stereotactic Ablative Fractionated Radiotherapy Versus Radiosurgery for Oligometastatic Neoplasia to the Lung (SAFRON) II Study Investigators. Single-Fraction vs Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases (SAFRON II): The Trans Tasman Radiation Oncology Group 13.01 Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1476-1485. doi: 10.1001/jamaoncol.2021.2939.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2015
• Primary Completion (Actual): July 27, 2020
• Study Completion (Actual): July 27, 2020

Study Registration Dates

• First Submitted: October 13, 2013
• First Submitted That Met QC Criteria: October 15, 2013
• First Posted (Estimate): October 18, 2013

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Neoplasia; Radiosurgery; SABR; Stereotactic Ablative Body Radiotherapy; Oligometastatic; Metastases to the Lung; Non Haematological
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: TROG 13.01 (Other Identifier: Trans Tasman Radiation Oncology Group); 13001 (Australasian Lung Trials Group); 1111-1136-6607 (Registry Identifier: WHO)