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Trial registered on ANZCTR


Registration number
ACTRN12613000746730
Ethics application status
Approved
Date submitted
2/07/2013
Date registered
4/07/2013
Date last updated
18/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A pilot study of two new imaging scans after high precision radiation therapy for patients with limited secondary spread of cancer to the lung.
Scientific title
A pilot study of Imaging in Stereotactic Ablative Frameless Radiosurgery for Oligometastatic Neoplasia to the lung.
Secondary ID [1] 282746 0
Nil
Universal Trial Number (UTN)
U1111-1145-0751
Trial acronym
SAFRON
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic cancer to the lung 289480 0
Condition category
Condition code
Cancer 289801 289801 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
If you participate in this study you will have two different types of scans as well as a single stereotactic body radiotherapy session (SBRT). The two types of scans we are researching are called a four-dimensional positron emission tomography (4D-PET) scan and a computed tomography (CT) perfusion scan.
Both scans are slow and recorded along with your breathing, which allows us to see how much your organs move as you breathe in and out. Each 4D-PET scan is broken down into many separate scans, each showing where your organs and the cancer are at a specific point of your breathing, for example, just as you start breathing in. For us to know whether you are breathing in or out, we will monitor your chest movement using breathing equipment. This will be done by either putting a belt around your chest or abdomen which senses your breathing, or a small lightweight reflective box on your chest and watch this using a special camera in the room. Both devices can tell us at which part of your breathing cycle each CT or PET image was taken, so we can make sets of images from each phase. Either device can be used during your scan, and this will depend on the particular machine on which you have your scan taken. The CT perfusion scan is similar to a standard CT scan, but is taken over a longer period of time with more contrast. This allows us to record the flow of contrast and blood flow into the cancer.
Specifically, the research involves:
1. Before treatment, you will have a four-dimensional positron emission tomography (4D-PET) scan and a computed tomography (CT) perfusion scan, as a baseline.
2. After treatment, you will have another 4D-PET scan and a CT perfusion scan at day 14 and day 70. These will be compared with the first scans in order to assess how your cancer responded to the treatment. Each scan will take approximately 30 minutes of time.
The stereotactic body radiotherapy (SBRT) treatment itself will routinely involve a third type of scan: a cone-beam CT. This scan is performed on the treatment machine, and is used to make the treatment more precise.
Specifically, the stereotactic radiotherapy treatment involves as standard:
3. Prior to treatment whilst being set-up on the treatment machine, a cone-beam CT will be used to check the position of the cancer. This will be repeated immediately before the treatment and again mid-way through the treatment (a total of 3 cone-beam CTs).
4. A single high-precision, high-dose radiotherapy (SBRT) treatment directed against the cancer. The treatment is a 26Gy single fraction. The treatment will take approximately 60 minutes.
Follow-up will involve a visit at approximately 2.5 to 3 months, and then at 6 months, 9 months, and 12 months from treatment. Participation in this study will involve no extra cost due to either having these scans or the treatment.
Intervention code [1] 287409 0
Diagnosis / Prognosis
Comparator / control treatment
Uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289875 0
To measure the accrual rate in order to assess the potential of escalation to larger studies
Timepoint [1] 289875 0
1 year after last patient treated on protocol
Secondary outcome [1] 303457 0
To measure the number of patients who complete the protocol imaging
Timepoint [1] 303457 0
The events recorded for this endpoint will be early response assessment imaging at 14 days +/- 3 days, and the definitive response assessment at 70 days +/- 10 days. A patient is deemed to successfully complete all protocol imaging studies only if he/she undergoes both the early and definitive response assessments.
Secondary outcome [2] 303458 0
To measure treatment toxicity (measured using CTCAE V4.0).
Pulmonary
Gastrointestinal
Skin/chest wall
Cardiac
Freedom from severe toxicity: time from landmark date until first recorded grade 4, or 5 toxicity
Timepoint [2] 303458 0
Assessed at the following time-points;
With 2 weeks of treatment completion.
Within 2 weeks of the date of definitive response assessment (70 days +/- 10 days).
6 months post-treatment.
9 months post-treatment.
12 months post-treatment.
Secondary outcome [3] 303459 0
To measure quality and reproducibility of the CT perfusion modality in the role of response assessment
Timepoint [3] 303459 0
The events recorded for this endpoint will be early response assessment imaging at 14 days +/- 3 days, and the definitive response assessment at 70 days +/- 10 days.

Eligibility
Key inclusion criteria
One or two metastases within the lung parenchyma.
Patients with primary cancers of epithelial, sarcomatoid or germ cell histologies who are treated with curative intent.
Aged 18 years or older.
ECOG performance of 0-2 inclusive.
The tumour must have a peripheral location, defined as at least 1cm beyond the mediastinum and beyond the bifurcation of the lobar bronchi.
Maximal tumour diameter < 5cm.
No known extrathoracic disease prior to enrollment. Primary is controlled.
Patient has provided written informed consent for participation in this trial prior to any protocol specific procedures.
Patient must be medically inoperable, have technically high risk disease for surgery or refuse surgery.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).
Any patient who is currently pregnant or breastfeeding.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The patient must meet all the inclusion criteria and none of the excluion criteria.
Participant Information and Consent form will be signed and dated.
This is a nonrandomised trial. There are no allocation concealment procedures.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nonrandomised trial
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
SAFRON is a single institution, single arm prospective feasibility study.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The study sample size is pragmatic and is based on the accrual rate necessary to successfully complete a larger study powered to assess the superiority of FDG-PET over standard CT in the response assessment of stereotactic radiotherapy of the lung.

We estimate that the accrual rate from this pilot will be slower than at the time of activating the larger proposed study. This is because referral patterns have yet to be established for this novel treatment that has only now become available in this country. We estimate that the accrual of 5-10 patients within 9 months at this early stage of the implementation of SBRT in this country will likely be sufficient to ensure adequate accrual to meet a target of at least 34 patients within 3 years.

The sample size for the larger study was calculated on the postulated superiority of post-therapy FDG-PET over post-therapy standard CT in predicting for overall survival. We estimate our event rate to be 45% at 2 years. The larger study trial timeline indicates that patients will have a mean follow-up of 3 years at the final analysis. Hazard ratios of the ability of FDG-PET to predict for overall survival in the presence of CT have been derived from our own institutional data in the setting of NSCLC .
The following assumptions are made for the purposes of performing the power calculation.
1.The hazard ratio for PET response when used in isolation to predict overall survival is consistent with that reported previously from our institution (i.e. HR ~= 3.1)
2.The hazard ratio for CT response when used in isolation to predict overall survival is similarly consistent with that reported in the same publication (i.e. HR ~= 2.3)
3.The strength of the association between PET response and CT response is also consistent with that reported in the same publications.

With a sample size of 45, and allowing for a type I error rate of 0.05, software simulations show that the power to conclude that PET adds significant prognostic value when used in addition to CT is equal to approximately 0.90. If accrual does not meet expected targets, then the study will still be powered to significance with 34 patients (~0.80).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/11/2010
Actual
4/11/2010
Date of last participant enrolment
Anticipated
9/02/2012
Actual
9/02/2012
Date of last data collection
Anticipated
Actual
30/01/2013
Sample size
Target
10
Accrual to date
Final
11
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1167 0
Peter MacCallum Cancer Institute - East Melbourne

Funding & Sponsors
Funding source category [1] 287546 0
Self funded/Unfunded
Name [1] 287546 0
Country [1] 287546 0
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre
Address
Locked Bag 1 A'Beckett St, Vic 8006
Country
Australia
Secondary sponsor category [1] 286299 0
None
Name [1] 286299 0
Address [1] 286299 0
Country [1] 286299 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289490 0
Peter MacCallum Cancer Centre HREC
Ethics committee address [1] 289490 0
Locked bag 1 A'Beckett St, Vic 8006
Ethics committee country [1] 289490 0
Australia
Date submitted for ethics approval [1] 289490 0
01/09/2010
Approval date [1] 289490 0
25/10/2010
Ethics approval number [1] 289490 0
Peter MacCallum HREC 10/80

Summary
Brief summary
Stereotactic body radiotherapy (SBRT) is an new form of cancer treatment involving highly precise radiotherapy. SBRT appears to be very effective in controlling cancer. After the treatment is given, however, with standard scans we have not been able to reliably assess how well the treatment worked. We propose to research SBRT with state-of-the-art scanning tools in patients with cancer spread to the lung. We aim to better understand how cancer responds to this therapy. This is the first step of the research, and is a small ‘pilot’ study. The ‘pilot’ is designed to assess whether the research can be completed.
Who is it for?
This trial is for patients who have cancer which has spread to the lung. We aim to enrol ten patients in total to participate in the research. These patients will be invited through Peter MacCallum at East Melbourne.
Trial details:
If you participate in this study you will have two different types of scans as well as a single stereotactic body radiotherapy session (SBRT). The two types of scans we are researching are called a four-dimensional positron emission tomography (4D-PET) scan and a computed tomography (CT) perfusion scan. Both scans are slow and recorded along with your breathing, which allows us to see how much your organs move as you breathe in and out. Each 4D-PET scan is broken down into many separate scans, each showing where your organs and the cancer are at a specific point of your breathing, for example, just as you start breathing in. For us to know whether you are breathing in or out, we will monitor your chest movement using breathing equipment. This will be done by either putting a belt around your chest or abdomen which senses your breathing, or a small lightweight reflective box on your chest and watch this using a special camera in the room. Both devices can tell us at which part of your breathing cycle each CT or PET image was taken, so we can make sets of images from each phase. Either device can be used during your scan, and this will depend on the particular machine on which you have your scan taken. The CT perfusion scan is similar to a standard CT scan, but is taken over a longer period of time with more contrast. This allows us to record the flow of contrast and blood flow into the cancer. Specifically, the research involves: 1. Before treatment, you will have a four-dimensional positron emission tomography (4D-PET) scan and a computed tomography (CT) perfusion scan, as a baseline. 2. After treatment, you will have another 4D-PET scan and a CT perfusion scan at day 14 and day 70. These will be compared with the first scans in order to assess how your cancer responded to the treatment. The stereotactic body radiotherapy (SBRT) treatment itself will routinely involve a third type of scan: a cone-beam CT. This scan is performed on the treatment machine, and is used to make the treatment more precise. Specifically, the stereotactic radiotherapy treatment involves as standard: 3. Prior to treatment whilst being set-up on the treatment machine, a cone-beam CT will be used to check the position of the cancer. This will be repeated immediately before the treatment and again mid-way through the treatment (a total of 3 cone-beam CTs). 4. A single high-precision, high-dose radiotherapy (SBRT) treatment directed against the cancer. Follow-up will involve a visit at approximately 2.5 to 3 months, and then at 6 months, 9 months, and 12 months from treatment. Participation in this study will involve no extra cost due to either having these scans or the treatment.
Trial website
Trial related presentations / publications
Publications:
1. Siva, Shankar, et al. "Implementation of a lung radiosurgery program: Technical considerations and quality assurance in an Australian institution." Journal of medical imaging and radiation oncology 56.3 (2012): 354-361.

2. Siva, Shankar, Michael MacManus, and David Ball. "Stereotactic radiotherapy for pulmonary oligometastases: a systematic review." Journal of Thoracic Oncology 5.7 (2010): 1091-1099.
Public notes

Contacts
Principal investigator
Name 41070 0
Dr Shankar Siva
Address 41070 0
Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Vic 8006
Country 41070 0
Australia
Phone 41070 0
+61 3 85595000
Fax 41070 0
+61 3 8559 7729
Email 41070 0
[email protected]
Contact person for public queries
Name 41071 0
Shankar Siva
Address 41071 0
Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Vic 8006
Country 41071 0
Australia
Phone 41071 0
+61 3 85595000
Fax 41071 0
+61 3 8559 7729
Email 41071 0
[email protected]
Contact person for scientific queries
Name 41072 0
Shankar Siva
Address 41072 0
Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, Vic 8006
Country 41072 0
Australia
Phone 41072 0
+61 3 85595000
Fax 41072 0
+61 3 8559 7729
Email 41072 0
[email protected]

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