Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001265662
Ethics application status
Approved
Date submitted
29/10/2014
Date registered
3/12/2014
Date last updated
18/02/2019
Date data sharing statement initially provided
18/02/2019
Date results information initially provided
18/02/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Outcomes and predictors of efficacy of palliative radiotherapy in patients with malignant pleural mesothelioma
Scientific title
The efficacy of palliative radiotherapy on symptomatic response as measured by PET scan and self-assessed pain response for patients with malignant pleural mesothelioma
Secondary ID [1] 285560 0
Nil Known
Universal Trial Number (UTN)
Nil
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
malignant pleural mesothelioma 293383 0
Condition category
Condition code
Cancer 293666 293666 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will undergo two 2-deoxy-2-[fluorine-18]fluoro- D-glucose Positron Emission Tomography Computerised Tomography (F18-FDG PET-CT) scans (one pre and one post radiotherapy). Participants will fast for 6 hours, have a blood glucose level and oxygen saturation level taken and an intravenous (IV) cannula inserted. A blood sample for biomarker analysis will be collected prior to each F18-FDG PET-CT scan. A dose of 200 MBq/m2 of F18-FDG will be administered via the IV cannula and participants are asked to wait quietly for 60 minutes for tracer uptake prior to scanning. The scan will take approx 30 minutes to complete. The same procedure will be followed for both pre and post radiotherapy F18-FDG PET-CT scans.
In addition to F18-FDG PET scans each participant will udergo one [F-18] fluoromisonidazole (F18-FMISO) Positron Emission Tomography - Computerised Tomography (PET-CT) scan pre-radiotherapy. Participants will not be required to fast. Oxygen saturation will be recorded prior to insertion of a IV cannula. Participants will receive F18-FMISO at a dose of 200 MBq/m2 via the IV cannula. After waiting 120 minutes for tracer uptake the PET-CT scan will be performed. This scan will take approximately 30 minutes to complete. There is only one F18-FMISO scan for this study.
All pre-radiotherapy scans are performed within 2 weeks of start of radiotherapy (and within one week of each other). The post-radiotherapy scan is performed 6 weeks after completion of radiotherapy
Participants will also undergo 2 x contrast enhanced thoracic CT scans to determine position and size of the lesions and response to radiotherapy. Pre-treatment CT scan will be within 2 weeks of commencement of radiotherapy and post-treatment CT scan will be 6 weeks post completion of radiotherapy.
Participants will undergo external beam radiotherapy with a total dose of 36 Gy delivered in 12 daily fractions of 3 Gy, 5 days per week, over 2.5 weeks
Intervention code [1] 290511 0
Diagnosis / Prognosis
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293481 0
Proportion of participants with a symptomatic response to radiotherapy at 6 weeks post treatment, as measured by a visual analogue pain score using the VAS numeric pain distress scale. Analgesic use measured by a patient medication questionnaire.
Timepoint [1] 293481 0
6 weeks post radiotherapy treatment
Secondary outcome [1] 311133 0
Change in health-related QOL scores using the EORTC QLQ-C30 and EORTC Quality of Life Questionnaire - LC13
Timepoint [1] 311133 0
At baseline, immediately pre and post radiotherapy, 3 weeks post-radiotherapy, 6 weeks post-radiotherapy and at 8 weekly follow up until cessation of study. Cessation of study will be until the participant's disease progresses or 6 months after the final participant is recruited (whichever is earliest
Secondary outcome [2] 311134 0
Duration of symptom responses will be measured by a visual analogue pain score using the VAS numeric pain distress scale
Timepoint [2] 311134 0
Measured post radiotherapy, 3 weeks post-radiotherapy, 6 weeks post radiotherapy and at 8 weekly follow up until cessation of study. Cessation of study will be until the participants disease progresses or 6 months after the final participant is recruited (whichever is earliest).
Secondary outcome [3] 311135 0
Objective radiological response by modified RECIST in the treated lesion
Timepoint [3] 311135 0
Determined from treatment date until cessation of study. Cessation of study will be until the participants disease progresses or 6 months after the final participant is recruited (whichever is earliest).
Secondary outcome [4] 311136 0
Objective response of treated lesion as measured by FDG PET-CT
Timepoint [4] 311136 0
Pre-radiotherapy and 6 weeks post-radiotherapy
Secondary outcome [5] 311137 0
Radiological time to progression (TTP) of treated lesions
Timepoint [5] 311137 0
Measured from study entry date until disease progression is determined as per modified RECIST
Secondary outcome [6] 311138 0
Correlation between measurement of hypoxia in F-MISO PET-CT scan and improvement in patient-rated outcome measures and analgesic requirements. Patient-rated outcomes measures will include the visual analogue pain scores, using the VAS numeric pain distress scale, and the analgesic medication questionnaires completed during the study.
Timepoint [6] 311138 0
Determined retrospectively at study conclusion, 6 months after the final patient is recruited.
Secondary outcome [7] 311139 0
Correlation between measurement of hypoxia in F-MISO PET-CT scan and objective response in treated lesion as measured by Modified RECIST Criteria (CT)
Timepoint [7] 311139 0
Determined retrospectively at study conclusion, 6 months after the final patient is recruited
Secondary outcome [8] 311140 0
Acute toxicity of RT as measured by NCI CTCAE V 4.0
Timepoint [8] 311140 0
Measured during radiotherapy treatment and post radiotherapy, 3 weeks post-radiotherapy, 6 weeks post-radiotherapy and at bimonthly follow up until cessation of study. Cessation of study will be until the participants disease progresses or 6 months after the final participant is recruited (whichever is earliest).

Eligibility
Key inclusion criteria
Patients with histologically or cytologically confirmed malignant pleural mesothelioma (MPM
Patients with focal clinical symptoms likely to be caused by MPM as confirmed by prior imaging imaging (including non-pleural metastatic disease)
Clinical indication to undergo palliative radiotherapy in the opinion of the treating physician
Able to undergo study procedures
More than 6 weeks post radiotherapy (at the time of the PET scan)
More than 6 weeks post chemotherapy or surgery (at the time of the PET scan), or 3 weeks is acceptable if disease has progressed on most recent chemotherapy.
Able to undergo study procedures
Lesion/s to be treated is/are radiologically measurable as per modified RECIST or RECIST
Baseline pain score on VAS greater than or equal to 4 AND/OR MED is greater or equal to 10mg/24 hours
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Currently receiving chemotherapy or radiotherapy
Radiotherapy to same site
Intention to commence chemotherapy < 6 weeks post radiotherapy
Pregnant or breastfeeding at the time of study enrolment
Unable to provide signed informed consent
Inadequate English language to complete study outcome measures
Medical contraindication to palliative radiotherapy
Geographically inaccessible for follow-up
Less than 18 years of age

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The proportion of patients who have a clinically significant reduction in the composite pain /analgesia score at 6 weeks post radiotherapy. Based on a one sided exact
binomial test with a minimum clinically meaningful response rate of 38% and an expected response rate of 60% at least 19 responders from 35 individuals is required to demonstrate a clinically relevant symptomatic response.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/12/2014
Actual
11/11/2014
Date of last participant enrolment
Anticipated
Actual
17/12/2017
Date of last data collection
Anticipated
5/05/2019
Actual
Sample size
Target
40
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 3095 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 8849 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 290165 0
Charities/Societies/Foundations
Name [1] 290165 0
Cancer Council Western Australia
Country [1] 290165 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Hospital Ave Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 288874 0
None
Name [1] 288874 0
Address [1] 288874 0
Country [1] 288874 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291872 0
Sir Charles Gairdner Group Human Research Ethics Committee and Research Governance
Ethics committee address [1] 291872 0
Level 2 A Block Hospital Ave Nedlands WA 6009
Ethics committee country [1] 291872 0
Australia
Date submitted for ethics approval [1] 291872 0
Approval date [1] 291872 0
06/05/2014
Ethics approval number [1] 291872 0
2014-001

Summary
Brief summary
The primary objective of this study is to demonstrate and prospectively quantify the palliative benefit of external beam radiotherapy to symptomatic mass in malignant pleural mesothelioma (MPM) in terms of patient rated benefits. Who is it for? You may be eligible to join this study if you are aged 18 years or above, have been diagnosed with malignant pleural mesothelioma and will undergo palliative radiotherapy. Study details All participants will receive the following scans in addition to their usual care: 2 F18-FDG PET-CT scans, 1 F18-FMISO PET-CT scan and 2 contrast-enhanced thoracic CT scans. The F18-FDG PET scans will require fasting for 6 hrs prior to the scan, a blood glucose level and an oxygen measurement will also be recorded. Prior to each scan a intravenous cannula will be inserted in to your arm and a 10ml blood sample will be collected for analysis of special biomarkers in a lab. The F18-FDG tracer will be injected into the IV cannula and you will be asked to rest for 60 minutes (for tracer uptake) prior to scanning. The scan should take approx 30 minutes to complete. One F18-FDG PET-CT scan will be performed within 2 weeks of the start of radiotherapy and one will be required 6 weeks after radiotherapy. One F18-FMISO PET-CT scan will be performed within 2 weeks prior to the start of radiotherapy (and within 1 week of the pre-radiotherapy FDG PET-CT scan). You will not need to fast for this scan. An IV cannula will be inserted and the tracer will be injected, you will need to wait for 120 minutes before the PET-CT scan is started. The scan should take approx 30 minutes. One contrast enhanced thoracic CT scan will be performed within 2 weeks prior to the start of radiotherapy and another will be performed 6 weeks after completion of radiotherapy to assess the response to the treatment. Participants will be followed up 3 weeks post radiotherapy, 6 weeks post-radiotherapy and then every 8 weeks to determine the symptomatic response to radiotherapy. Follow up will occur as part of your normal outpatient visits and will involve completion of pain scores and quality of life and medication questionnaires. You will attend follow-up appointments every 8 weeks until you require additional treatment (such as increased pain medication or chemotherapy) or until 6 months after the last study participant has been recruited (whichever is earliest). Using an integrated approach (including innovative imaging techniques that target different tumour characteristics (F-MISO PET, FDG PET), biomarkers and plausible and established clinical markers) this study will also examine the role of hypoxia as imaged by F-MISO PET in radio resistance of symptomatic mass lesions in MPM and identify other clinical and biological predictors of response to radiotherapy. We hypothesise that greater lesion hypoxia, anaemia, and systemic hypoxaemia will be associated with lower radiological response rates and both poorer and shorter duration of symptom control
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52370 0
Prof Anna Nowak
Address 52370 0
M503, School of Medicine and Pharmacology, University of Western Australia, 35 Stirling Hwy Crawley WA 6009
Country 52370 0
Australia
Phone 52370 0
+61 8 6457 3333
Fax 52370 0
+61 8 6457 3610
Email 52370 0
[email protected]
Contact person for public queries
Name 52371 0
Prof Anna Nowak
Address 52371 0
M503, School of Medicine and Pharmacology University of Western Australia, 35 Stirling Hwy Crawley WA 6009
Country 52371 0
Australia
Phone 52371 0
+61864573333
Fax 52371 0
+61 8 6457 3610
Email 52371 0
[email protected]
Contact person for scientific queries
Name 52372 0
Prof Anna Nowak
Address 52372 0
M503, School of Medicine and Pharmacology, University of Western Australia, 35 Stirling Hwy Crawley WA 6009
Country 52372 0
Australia
Phone 52372 0
+61864573333
Fax 52372 0
+61 8 6457 3610
Email 52372 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.