Please note that the ANZCTR website will be unavailable from 3pm until 3.30pm (AEST) on Thursday 24th August for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

Trial registered on ANZCTR


Trial ID
ACTRN12617000166370
Ethics application status
Approved
Date submitted
25/01/2017
Date registered
31/01/2017
Date last updated
14/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised phase 3 trial of Palliative care Early in Advanced Lung Cancers.
Scientific title
Efficacy of early referral to palliative care for improving quality of life and health care resources following recent diagnosis of advanced thoracic maglignancies.
Secondary ID [1] 290628 0
CTC 0145/ALTG 13/008
Universal Trial Number (UTN)
Trial acronym
PEARL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adults with advanced thoracic malignancy (NSCLC, SCLC or
MPM) that have been newly diagnosed within the last 60 days.
301138 0
Condition category
Condition code
Cancer 300902 300902 0 0
Lung - Small cell
Cancer 300903 300903 0 0
Lung - Non small cell
Cancer 300904 300904 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Standard oncological care plus early referral (within 7 days of randomisation) to a
hospital-based palliative care service for the specified palliative care intervention (first consultation within 60 days of the diagnosis of advanced lung cancer or mesothelioma). The intervention is the early referral to palliative care - there is no change to the palliative care received, which is at the discretion of the treating physician until patient death.
Intervention code [1] 296503 0
Treatment: Other
Comparator / control treatment
Standard oncological care plus referral to a hospital based palliative care service, the timing of which is determined at the treating clinician’s discretion.
Control group
Active

Outcomes
Primary outcome [1] 300313 0
Proportion of participants with a clinically important improvement in health-related quality of life (HRQL), defined as an improvement of 5 points or more from baseline on the Functional Assessment of Cancer Therapy-Lung (FACT-L) Trials Outcomes Index (TOI) maintained for at least 2 consecutive assessments within 6 months from randomisation.
Timepoint [1] 300313 0
Baseline (which is up to 7 days prior to randomisation) and every 3-4 weeks up until 24 weeks post-randomisation and then every 6-8 weeks until patient's death.
Secondary outcome [1] 329666 0
The change in quality of life using score on FACT-L TOI
Timepoint [1] 329666 0
Baseline compared to 12 weeks post-randomisation
Secondary outcome [2] 329667 0
Composite outcome of healthcare resource use, costs and incremental cost effectiveness to determine the incremental cost-effectiveness and cost-utility of early referral to palliative care versus discretionary referral.
The following health-care resource usage will be collected for assessment:
* Hospitalisations or emergency department presentations (for all participants by trial staff via a standard (e)CRF),
* Visits to health professionals (for Australian participants via Medical Benefits Schedule (MBS)), and;
* Medications (for Australian participants via Pharmaceutical Benefits Scheme (PBS)).
Timepoint [2] 329667 0
From date of randomisation to death or end of trial.
Secondary outcome [3] 329668 0
Composite outcome of specific aspects of HRQL including depression, anxiety, lung cancer symptoms and overall HRQL (FACT-L, PROMIS-ED, EQ-5D-5L, ICECAP-SCM and patient good days diary)
Timepoint [3] 329668 0
The FACT-L, EQ-5D-5L and ICECAP-SCM questionnaires as well as the patient good days diary are assessed at Baseline and every 3-4 weeks up until 24 weeks post-randomisation and then every 6-8 weeks until the patient's death.
The PROMIS-ED questionnaire is assessed at Baseline, at 6-8 weeks post-randomisation, at 12-16 weeks post-randomisation and then every 12 weeks until the patient's death.
Secondary outcome [4] 329669 0
Overall survival
Timepoint [4] 329669 0
OS is defined as the interval from the date of randomisation to date of death from any cause or to a minimum of 6 months post randomisation.
Secondary outcome [5] 329670 0
Composite of carer related outcomes including carer satisfaction and carer burden from Carer Reaction Assessment (CRA), Clinical Care Tasks measure (CCT), FAMCARE-2, Quality of Death and Dying Questionnaire (QODD).
Timepoint [5] 329670 0
The CRA and CCT questionnaires are assessed at Baseline and every 3-4 weeks up until 24 weeks post-randomisation (of the patient) and then every 6-8 weeks until the patient's death.
The FAMCARE-2 questionnaire is assessed at 6-8 weeks post-randomisation, at 12-16 weeks post-randomisation and then every 12 weeks until the patient's death.
The QODD questionnaire is assessed at 6-12 weeks after the patient's death.
Secondary outcome [6] 329671 0
Patient and carer understanding of illness and prognosis (using a non-validated 2-item questionnaire used in Temel et al, 2011)
Timepoint [6] 329671 0
The Patient and carer understanding of illness and prognosis is assessed at Baseline and every 3-4 weeks up until 24 weeks post-randomisation (of the patient) and then every 6-8 weeks until the patient's death.
Secondary outcome [7] 329672 0
Quality of end of life care, including use of advance care plans (ACP) and the use of aggressive therapies in the last month of life obtained from the patient's medical record.
Timepoint [7] 329672 0
Following death of participant
Secondary outcome [8] 331169 0
Quality-adjusted overall survival (using the EQ-5D-5L questionnaire)
Timepoint [8] 331169 0
The EQ-5D-5L questionnaire is assessed at Baseline and every 3-4 weeks up until 24 weeks post-randomisation and then every 6-8 weeks until the patient's death.

Eligibility
Key inclusion criteria
1. Adults, aged 18 years and older, with a histological or cytological diagnosis within the last
60 days of either:
(a) Advanced NSCLC (this includes de novo stage IV disease, recurrent NSCLC after definitive treatment, and locally advanced disease which is not planned for curative
treatment), or
(b) Extensive stage SCLC, or
(c) Advanced MPM which is not planned for extrapleural pneumonectomy or pleurectomydecortication.

2. Australia-modified Karnofsky performance status of 50 to 100 at the time of randomisation

3. Willing and able to comply with all study requirements, including ability at the time of
screening to complete the QOL questionnaires without assistance, in accordance with
protocol requirements.

4. Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Immediate referral to palliative care required, or already referred to palliative care (this
includes referral to a community or hospital based palliative care service, or palliative care
physician).

2. Life expectancy of less than 3 months.

3. Serious medical or psychiatric onditions that might limit the ability of the patient to comply with the protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation by Flexetrials randomisation software.
Stratified allocation employed.
Patients are stratified using:
1. Cancer type non-small cell lung cancer (NSCLC) which is EGFR or ALK mutation positive
versus NSCLC which is EGFR and ALK mutation negative/unknown versus small cell lung
cancer (SCLC) versus malignant pleural mesothelioma (MPM)
2. Gender
3. Age (younger than 70 years vs 70 years and older)
4. Planned or current use of chemotherapy
5. Australia-modified Karnofsky performance status (70 or lower vs 80 and above)
6. Study site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary endpoint for this trial is a clinically important improvement in the FACT-L TOI. This is defined as an improvement of 5 points or more from baseline, which is maintained for at least 2 consecutive assessments. The proportion of patients in each arm who achieve the primary endpoint will be reported along with two-sided 95% confidence intervals. A chi-squared test of independence will be performed to test the null hypothesis that the proportions are equal against a two-sided alternative, using a 5%
significance level. Supplementary analyses will include adjustment for stratification factors that were used in the randomisation, as well as consider changes in the raw TOI score over time.

Analyses of secondary endpoints will be performed according to the same principles. Binary outcomes will be presented as proportions and compared using chi-squared tests of independence. Continuous outcomes will be summarised by means or medians and compared using independent t-tests or Wilcoxon rank-sum tests, as appropriate. Time-to-event outcomes will be presented using Kaplan-Meier estimates and compared using a log-rank test. A two-sided 5% significance level will be used for all tests and there
will be no formal adjustment for multiple comparisons, but statistically significant differences in secondary outcomes will be interpreted conservatively, particularly if the primary analysis is non-significant. Supplementary subgroup and adjusted analyses will be defined in the statistical analysis plan.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 7012 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 7013 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 7015 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [4] 7018 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [5] 7019 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [6] 7020 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [7] 7022 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [8] 7023 0
Concord Repatriation Hospital - Concord
Recruitment hospital [9] 7024 0
St John of God Midland Public Hospital - Midland
Recruitment hospital [10] 7025 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [11] 7026 0
Toowoomba Hospital - Toowoomba
Recruitment hospital [12] 7027 0
The Prince Charles Hospital - Chermside
Recruitment hospital [13] 7028 0
Maryborough Hospital - Maryborough
Recruitment hospital [14] 7029 0
The Townsville Hospital - Douglas
Recruitment hospital [15] 7030 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [16] 7031 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [17] 7333 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 14744 0
3000 - Melbourne
Recruitment postcode(s) [2] 14745 0
3168 - Clayton
Recruitment postcode(s) [3] 14747 0
3220 - Geelong
Recruitment postcode(s) [4] 14750 0
3050 - Parkville
Recruitment postcode(s) [5] 14751 0
2065 - St Leonards
Recruitment postcode(s) [6] 14752 0
2485 - Tweed Heads
Recruitment postcode(s) [7] 14754 0
2560 - Campbelltown
Recruitment postcode(s) [8] 14755 0
2139 - Concord
Recruitment postcode(s) [9] 14756 0
6056 - Midland
Recruitment postcode(s) [10] 14757 0
6009 - Nedlands
Recruitment postcode(s) [11] 14758 0
4350 - Toowoomba
Recruitment postcode(s) [12] 14759 0
4032 - Chermside
Recruitment postcode(s) [13] 14760 0
4650 - Maryborough
Recruitment postcode(s) [14] 14761 0
4814 - Douglas
Recruitment postcode(s) [15] 14762 0
2050 - Camperdown
Recruitment postcode(s) [16] 15119 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 8425 0
New Zealand
State/province [1] 8425 0
South Island

Funding & Sponsors
Funding source category [1] 295131 0
Government body
Name [1] 295131 0
Cancer Australia
Address [1] 295131 0
Level 14, 300 Elizabeth Street
SYDNEY
NSW 2000
Country [1] 295131 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown
NSW 1450
Country
Australia
Secondary sponsor category [1] 293949 0
None
Name [1] 293949 0
Address [1] 293949 0
Country [1] 293949 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296479 0
Sydney Local Heatlh District (RPAH Zone) Ethics Review Committee
Ethics committee address [1] 296479 0
Research Ethics and Governance Office
Royal Prince Alfred Hospital
Missenden Road
Camperdown
NSW 2050
Ethics committee country [1] 296479 0
Australia
Date submitted for ethics approval [1] 296479 0
08/08/2016
Approval date [1] 296479 0
25/10/2016
Ethics approval number [1] 296479 0
X16-0340 & HREC/16/RPAH/467

Summary
Brief summary
The primary purpose of this trial is to evaluate whether early referral for palliative care can improve quality of life, cost effectiveness and quality of end of life care for adults who are newly diagnosed with advanced lung cancer.

Who is it for?
You may be eligible to enroll in this trial if you are aged 18 or over and have been diagnosed with advanced non-small cell lung cancer, extensive small cell lung cancer or advanced malignant pleural mesothelioma within the last 60 days.

Study details
All participants enrolled in this trial will be randomly allocated (by chance) to receive either standard care referral to palliative care at the discretion of the treating oncologist, or to receive early referral to palliative care within 7 days of enrolling in this trial. With the exception of the timing of the referral, the palliative care received by each group will be as per standard care, with information and care provided by the palliative care team as required for each participant.

Participants will be asked to complete a number of questionnaires relating to quality of life and cancer symptoms at regular time points until their death. Carers will be asked to complete quality of life and death questionnaires and an interview at regular intervals up to six months following participant death.

It is anticipated that the findings from this trial will provide information on whether early referral to palliative care following diagnosis of advanced lung cancer is beneficial for patient quality of life and end of life, and cost-effectiveness of care.
Trial website
Trial related presentations / publications
Public notes
Patients will be asked at screening to nominate a carer who would be willing to complete study assessments. A carer may be any person (including a relative or friend) whom the patient:
(a) Perceives to be their main support person (primary carer)
(b) Agrees for the research team to approach for potential research participation; and
(c) Is agreeable to have their medical information shared.
Written informed consent must be signed and dated by the carer, and signed and dated by the Investigator, prior to any trial-specific carer assessments being completed.
It is preferable for patients to have a nominated carer however patients unable to nominate a carer who are willing to complete the trial assessments will still be eligible for the trial.
Attachments [1] 1307 1307 0 0
http://www.anzctr.org.au/AnzctrAttachments/371931-PEARL_Protocol_V1.0_dated_050816.pdf (Protocol)
Attachments [3] 1309 1309 0 0

Contacts
Principal investigator
Name 70782 0
A/Prof Linda Mileshkin
Address 70782 0
Peter MacCallum Cancer Centre
305 Grattan Street,
Melbourne VIC 3000
Country 70782 0
Australia
Phone 70782 0
+61 3 8559 5000
Fax 70782 0
+61 3 8559 7739
Email 70782 0
linda.mileshkin@petermac.org
Contact person for public queries
Name 70783 0
Mr David Cannan
Address 70783 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 70783 0
Australia
Phone 70783 0
+61 2 9562 5000
Fax 70783 0
+61 2 9562 5094
Email 70783 0
pearl@ctc.usyd.edu.au
Contact person for scientific queries
Name 70784 0
A/Prof Linda Mileshkin
Address 70784 0
c/o PEARL Study Team
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 70784 0
Australia
Phone 70784 0
+61 2 9562 5000
Fax 70784 0
+61 2 9562 5094
Email 70784 0
pearl@ctc.usyd.edu.au