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Trial registered on ANZCTR


Registration number
ACTRN12621000221853
Ethics application status
Approved
Date submitted
11/12/2020
Date registered
3/03/2021
Date last updated
3/03/2021
Date data sharing statement initially provided
3/03/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
ASPiRATION - An observational cohort study assessing the clinical impact of comprehensive genomic profiling in people with newly diagnosed metastatic lung cancer.
Scientific title
An observational cohort study to assess the clinical impact of comprehensive genomic profiling in metastatic lung cancer patients (ASPiRATION).
Secondary ID [1] 302967 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ASPiRATION
Linked study record
This trial is a subprogram of ACTRN12616000908437.

Health condition
Health condition(s) or problem(s) studied:
Metastatic lung cancer 320017 0
Metastatic non-squamous non-small cell lung cancer (mNSCLC) 320018 0
Condition category
Condition code
Cancer 317939 317939 0 0
Lung - Non small cell

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Molecular screening for actionable biomarkers to be used to guide therapy.
In parallel with standard of care (SoC) testing (e.g. IHC/FISH/PCR for EGFR, ALK and ROS1), Comprehensive Genomic Profiling (CGP) will be performed on tumour tissue after patient consent and assessment of suitability for the study. Existing ‘biobanked’ tissue samples will be used. A report containing any actionable genomic alterations and corresponding treatment recommendations will be issued to the treating clinician
As part of the study participants will be asked to complete a series of questionnaires assessing health-related quality of life and psychosocial status. EuroQOL EQ-5D-5L quality of life and visual analogue scale will be measured at 5 timepoints: at time of patient consent to molecular screening in the ASPiRATION subprogram, at return of molecular screening report to treating clinician, and 6, 12 and 24 months after consent for molecular screening.
The Garvan Institute of Medical Research will coordinate the molecular screening from archival tumour tissue. The core assays will be based on a genomic sequencing panel to cover a broad range of potentially actionable or biologically important cancer genes, with subsequent bioinformatics analysis. Examples of genes that will be assessed by CGP include BRAF non-V600, METex14, NTRK and many others. Patient tumour samples will also be assessed for biomarkers using relevant assays such as immunohistochemistry.
Molecular screening results will be reviewed by a Molecular Tumour Board (MTB). The MTB is composed of suitably qualified clinical and basic science researchers with expertise in oncology, clinical trials, cancer biology, genomics, bioinformatics, molecular pathology, and clinical genetics. In addition, ex officio and ad hoc expertise may be called on to assist the MTB in decision-making. MTB members are either affiliated with the Garvan Institute of Medical Research, or an institute/hospital within the AGCMC network. MTB members attend an annual MTB masterclass, and sign a confidentiality deed poll prior to attendance.
Options for treatment as a result of the screening will fall into 3 categories:
1. Targeted treatments currently reimbursed by the Australian government under the PBS;
2. Treatment on a MoST substudy or other clinical trials;
3. Expanded access programs, hospital or patient funded access to targeted treatments
Participants who do not have an 'actionable' genomic alteration on SoC and CGP may be treated at the discretion of the treating clinician.
As well as first line treatment, CGP results may also guide 2nd and subsequent lines of therapy at the discretion of the treating clinician.
Subsequent molecular screening is not planned as part of this study. Repeat tissue sample acquisition may be considered by participant’s treating clinician if initial tumour tissue was not sufficient to obtain evaluable results. Study duration is expected as 4 years in total (2 years of recruitment and 2 years follow-up after consent to molecular screening).
Intervention code [1] 319255 0
Early Detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325943 0
This is a composite primary outcome.
To investigate whether routine Comprehensive Genomic Profiling (CGP) can be integrated into Australian clinical practice for metastatic non-squamous non-small cell lung cancer (mNSCLC) patients by assessing:
a) the impact of CGP in generating actionable genomic information to personalise clinical decision making will be assessed via evaluating actionable genomic alterations, emerging targeted treatments and evaluable results by CGP and SOC testing. This will be performed by evaluating SoC testing reports, MTB reports and information provided by participant’s treating clinician.
b) feasibility considerations, including time to receipt of CGP results to inform clinical care will be assessed via evaluating turnaround time for SoC and CGP testing, repeat biopsy rates and percentage of patients commencing treatment prior to receiving CGP results. This will be performed by evaluating timepoints associated with consent, SoC and CGP testing, associated reports and information provided by participant’s treating clinician.
Timepoint [1] 325943 0
Components of the primary outcome will be assessed as follows:
a) the impact of CGP in generating actionable genomic information to personalise clinical decision making measured via:
- Actionable genomic alterations : The percentage of patients with actionable genomic alterations found using CGP and SoC testing methods. Assessed based on the results of Standard of Care (SoC) testing and Molecular Tumour Board report (MTB).
- Emerging targeted treatments: The percentage of patients receiving emerging targeted treatments (MoST clinical trials, other clinical studies or other access programs). Assessed via treatment information provided by participant’s treating clinician.
- Evaluable results by CGP and SoC testing: The percentage of patients with evaluable results by CGP and SoC testing. Assessed based on the results of Standard of Care (SoC) testing and Molecular Tumour Board report (MTB).

b) feasibility considerations, including time to receipt of CGP results to inform clinical care.
- Turnaround Time : Time taken for CGP and SoC testing results to be made available, defined as:
i) the interval from the date of molecular screening consent to date MTB report returned to
clinician.
ii) the interval from date of archival tissue request to date MTB report returned to clinician.
iii) the interval from receipt of tissue at central molecular screening laboratory date of MTB report
returned to clinician.
iv) The interval from confirmation of sufficient tissue for molecular screening by the central
molecular screening laboratory to date MTB report returned clinician.
- Repeat biopsy rates : The percentage of patients requiring repeat biopsy to obtain evaluable results by CGP and SoC testing. Assessed via information provided by participant’s treating clinician.
- The percentage of patients commencing treatment prior to receiving CGP results. Assessed via information provided by participant’s treating clinician. Data sources may include (but not limited to) medical records, state-based cancer registries, the national mortality registry, via contact of participants, their general practitioner or treating clinician.
Secondary outcome [1] 389627 0
To investigate the impact of Comprehensive Genomic Profiling (CGP) in the Australian context by assessing the change in treatment recommendation with CGP results. This will be performed by evaluating the information provided by participant’s treating clinician about the participant’s treatment plan changes. Assessed via information from (not limited to) participant’s medical records, via contact of participant, their general practitioner or treating clinician.
Timepoint [1] 389627 0
For the duration of the study, estimated at 4 years. The change in treatment recommendation with CGP results will be reviewed regularly and at least annually.
Secondary outcome [2] 390573 0
To investigate the impact of Comprehensive Genomic Profiling (CGP) in the Australian context by assessing the impact of CGP on clinical trial participation of investigational agent(s). This will be performed by evaluating the information provided by participant’s treating clinician about the patients who entered a clinical trial of an investigational agent(s) informed by CGP. Assessed via information from (not limited to) participant's medical records, via contact of participant, their general practitioner or treating clinician.
Timepoint [2] 390573 0
For the duration of the study, estimated at 4 years. The impact of CGP on clinical trial participation of investigational agent(s) will be reviewed regularly and at least annually.
Secondary outcome [3] 390574 0
To investigate the impact of Comprehensive Genomic Profiling (CGP) in the Australian context by assessing the clinical outcome measures. This will be performed by evaluating the time on first-line, second-line and third line treatment and therapies received via the information provided by participant’s treating clinician. Assessed via information from (not limited to) participant's medical records, via contact of participant, their general practitioner or treating clinician.
Timepoint [3] 390574 0
For the duration of the study, estimated at 4 years. The clinical outcome measures will be reviewed regularly and at least annually.
Secondary outcome [4] 390575 0
To investigate the impact of Comprehensive Genomic Profiling (CGP) in the Australian context by assessing healthcare resource use and costs. This will be performed by evaluating administrative data from diagnostic investigations and imaging, outpatient appointments, and visits to specialist and primary care health professionals [for Australian participants via Medical Benefits Schedule (MBS)], and medications [for Australian participants via Pharmaceutical Benefits Scheme (PBS)].
Timepoint [4] 390575 0
Information on the following areas of healthcare resource use using administrative data will be collected over a minimum 4 year timeframe, commencing up to 6 months prior to screening consent.. The healthcare resource use and costs will be reviewed regularly and at least annually.
Secondary outcome [5] 390576 0
To investigate the impact of Comprehensive Genomic Profiling (CGP) in the Australian context by assessing health-related quality of life. This will be performed by using EuroQOL EQ-5D-5L quality of life questionnaire and visual analogue scale.
Timepoint [5] 390576 0
Health-related quality of life will be measured at 5 timepoints: at time of patient consent to molecular screening in the ASPiRATION subprogram, at return of molecular screening report to treating clinician, and 6, 12 and 24 months after consent for molecular screening.
Secondary outcome [6] 390577 0
To investigate the impact of Comprehensive Genomic Profiling (CGP) in the Australian context by assessing cost-effectiveness of CGP. This will be performed by evaluating health-related quality of life questionnaires, if appropriate. Information on the following areas of healthcare resource use using administrative data will be collected: diagnostic investigations and imaging, outpatient appointments, and visits to specialist and primary care health professionals [for Australian participants via Medical Benefits Schedule (MBS)], and medications [for Australian participants via Pharmaceutical Benefits Scheme (PBS)]. Consent will be sought from Australian participants for linkage to their Medicare MBS and PBS records, using the approved Services Australia (DHS) form.
Timepoint [6] 390577 0
For the duration of the study, estimated at 4 years and commencing up to 6 months prior to screening). The cost-effectiveness of CGP will be reviewed regularly and at least annually.
Secondary outcome [7] 390578 0
To investigate the impact of Comprehensive Genomic Profiling (CGP) in the Australian context by assessing collection of biospecimens for research. This will be performed by evaluating the percentage of patients where biospecimens (tissue and blood) are collected for translational research. Assessed via information provided in the study database by participating hospital sites on the sample type, sample protocol timepoint and sample collection details.
Timepoint [7] 390578 0
For the duration of the study, estimated at 4 years. Collection of biospecimens for research will be reviewed regularly and at least annually.

Eligibility
Key inclusion criteria
1. Male or female patients, aged 18 years and older, with newly diagnosed pathologically confirmed metastatic non-squamous non-small cell lung cancer (mNSCLC);
a. Exception: patients with a typical pattern of disease recurrence within 12 months following primary resection may not require a confirmatory repeat biopsy, unless the diagnosis is unclear, such as an isolated pulmonary nodule, in which case repeat biopsy should be considered per standard practice;
b. For mixed or other histologies the following is permitted:
- Mixed adenosquamous where adenocarcinoma is dominant
- Carcinoma not otherwise specified (NOS) favouring adenocarcinoma
- Sarcomatoid carcinoma
2. ECOG performance status 0 or 1.
3. Sufficient tissue for molecular screening.
4. Willing and able to comply with study requirements. It is the intention to screen patients who are in principle willing to consider participation in a MoST substudy if they are found to have an appropriate tumour biomarker and are still eligible for enrolment at the time of the treatment phase;
5. Current enrolment or participation in another clinical study with an unregistered investigational product during the last 12 months, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study, must first be discussed the Study Team before study enrolment.
6. Signed, written informed consent to participate in molecular profiling and linkage to Medicare data.
7. Have not had any previous treatment for metastatic non-squamous NSCLC;
a. For patients with symptomatic or bulky disease, where it would be detrimental to delay treatment, systemic therapy may be commenced at the investigator’s discretion whilst awaiting CGP results;
b. Patients who have had prior treatment with curable intent are eligible.
8. Life expectancy of at least 12 weeks.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Ineligible histology:
- Mixed small cell lung cancer
- Large cell neuroendocrine carcinoma
2. Comorbidities or conditions (e.g. psychiatric) which may contraindicate participation and/or ability to receive any systemic therapy(s);
3. Comorbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
4. History of another primary malignancy except for:
a. Malignancy treated with curative intent and with no known active disease within 2 years before consent to molecular screening and of low potential risk for recurrence
b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
c. Adequately treated carcinoma in situ without evidence of disease

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

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
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 307385 0
Government body
Name [1] 307385 0
Office for Health and Medical Research
Address [1] 307385 0
Locked Mail Bag 961
North Sydney NSW 2059
Country [1] 307385 0
Australia
Funding source category [2] 307386 0
Commercial sector/Industry
Name [2] 307386 0
Roche Products Pty limited
Address [2] 307386 0
30-34 Hickson Road
Sydney NSW 2000
Country [2] 307386 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australian Genomic Cancer Medicine Centre
Address
Kinghorn Cancer Centre,
370 Victoria Street,
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 308041 0
University
Name [1] 308041 0
University of Sydney
Address [1] 308041 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country [1] 308041 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307472 0
St Vincent's Hospital Sydney Human Research Ethics Committee
Ethics committee address [1] 307472 0
390 Victoria Street
Darlinghurst NSW 2010
Ethics committee country [1] 307472 0
Australia
Date submitted for ethics approval [1] 307472 0
Approval date [1] 307472 0
21/05/2020
Ethics approval number [1] 307472 0

Summary
Brief summary
What is ASPiRATION?
ASPiRATION is a clinical trial that is testing a new approach to providing personalised treatments for patients with newly diagnosed lung cancer through comprehensive genomic testing of patient’s tumour tissue. The ASPiRATION study is being conducted as part of a larger research project called the Molecular Screening and Therapeutics (MoST) Program.
In Australia, standard of care tumour testing for lung cancer patients has the ability to identify changes in three genes: EGFR, ALK & ROS1, for which drugs are available on the Pharmaceutical Benefits Scheme (PBS). If a patient is suitable for ASPiRATION, their tumour will also be tested using a technique called comprehensive genomic profiling (CGP), often referred to as molecular screening and/or profiling. This technique allows to look at changes in hundreds of genes in a single test. After a patient’s tumour is tested, a report is sent to the referring oncologist with information on (i) Any genetic biomarkers that were identified in the tumour and (ii) The types of treatment that may be suitable.
Who is it for?
a. Adults (>= 18 years of age) with newly diagnosed pathologically confirmed non-squamous non-small cell lung cancer and sufficient tumour tissue for “molecular” testing
b. Fit to be able to have treatment
Study details: A small part of your tumour tissue, which was collected previously, will be used to identify a biomarker by doing a laboratory analysis (‘molecular screening’). You will be asked to provide information about your and your family’s health background, to donate a blood sample and complete some questionnaires.
Results from molecular screening will be returned to all participants. These results may have implications for your treatment if a suitable biomarker is found.
It is hoped this research will determine whether additional molecular screening can be feasibly integrated into Australian clinical practice for patients with metastatic non-squamous non-small cell lung cancer (mNSCLC).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107350 0
A/Prof Nick Pavlakis
Address 107350 0
Royal North Shore Hospital
Reserve Rd
St Leonards
NSW 2065
Country 107350 0
Australia
Phone 107350 0
+61294631172
Fax 107350 0
Email 107350 0
nick.pavlakis@sydney.edu.au
Contact person for public queries
Name 107351 0
Ms Mariya Walker
Address 107351 0
NHMRC Clinical Trials Centre
Level 6, Chris O'Brien Lifehouse
119–143 Missenden Road
Camperdown NSW 2050
Country 107351 0
Australia
Phone 107351 0
+61295625000
Fax 107351 0
Email 107351 0
most@ctc.usyd.edu.au
Contact person for scientific queries
Name 107352 0
Prof Benjamin Solomon
Address 107352 0
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne
VIC 3000
Country 107352 0
Australia
Phone 107352 0
+61385595000
Fax 107352 0
Email 107352 0
Ben.Solomon@petermac.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Currently no plan and participant consent will be required.
What supporting documents are/will be available?
No other documents available
Summary results
No Results