Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000226606
Ethics application status
Approved
Date submitted
9/02/2023
Date registered
3/03/2023
Date last updated
7/07/2023
Date data sharing statement initially provided
3/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Dynamic liquid molecular profiling in anaplastic lymphoma kinase (ALK) Non-Small Cell Lung Cancer
Scientific title
DYNAMALK: Dynamic ctDNA profiling in ALK+ Non-Small Cell Lung Cancer (NSCLC) : a study of the Australian Registry and Biobank of Thoracic Cancers (AURORA)
Secondary ID [1] 308954 0
None
Universal Trial Number (UTN)
U1111-1288-1952
Trial acronym
DYNAMALK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced ALK+ NSCLC 328966 0
Condition category
Condition code
Cancer 325951 325951 0 0
Lung - Non small cell

Intervention/exposure
Study type
Observational
Patient registry
True
Target follow-up duration
36
Target follow-up type
Months
Description of intervention(s) / exposure
ctDNA profiling at three time points: (1) baseline, (2) +6-12 weeks coinciding with first on treatment imaging, (3) +24 months OR at disease progression whichever occurs first.

ctDNA profiling will involve provision of a single blood sample at each of the three time-points. Samples will be collected at the hospital of enrolment to be sent for centralised testing and reporting. Treating clinicians and patients will be provided real-time results from ctDNA profiling with decision to impact standard of care prescribing at the discretion of the treating clinician. Tissue samples will be obtained from standard care biopsies when available.

DYNAMALK is an AURORA sub-study with participation requiring enrolment in AURORA. Existing AURORA participants will be screened for DYNAMALK eligibility and offered participation. Non-AURORA patients can be enrolled into AURORA by their treating clinician specifically to participate in DYNAMALK.

DYNAMALK includes two arms based on standard of care treatment initiated by the treating clinician. Participants in ARM A will receive lorlatinib as first line treatment. Lorlatinib is being delivered as standard of care and access to lorlatinib is not reliant on participation in this profiling study. Participants in arm B will have received at least one prior ALK directed therapy as part of standard of care management. There is no requirement for duration or recency of prior ALK treatments. Prior treatment with chemotherapy or immunotherapy does not preclude participation.
Intervention code [1] 325402 0
Diagnosis / Prognosis
Comparator / control treatment
No control group. This study has two parallel arms and outcomes will be reported separately for each arm. It is not designed to compare outcomes between arms. Outcomes within each group will be indirectly compared against published studies post-hoc.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333804 0
Description of the detailed clinicopathologic, baseline and temporal plasma ctDNA next-generation sequencing profiles
Timepoint [1] 333804 0
36 months months post-enrolment
Primary outcome [2] 333875 0
Proportion of participants with changes in clinical management of ALK+ NSCLC based on their ctDNA profile results.

Changes in clinical management will be documented by the treating clinician and may include change in imaging or other monitoring schedule, or change in therapy.
Timepoint [2] 333875 0
36 months months post-enrolment
Secondary outcome [1] 418344 0
Consent to participate rate *uptake (%, patients enrolled in study/ patients offered study enrolment) *Local feasibility

Consent rate will be ascertained by audit of study enrolment/withdrawal logs to determine the number of participants enrolled vs. the number of participants approached for enrolment.
Timepoint [1] 418344 0
After last participant enrolment (estimated 16 months after study opened for enrolment)
Secondary outcome [2] 418345 0
Concordance of ALK plasma molecular results compared to ALK tissue molecular results by standard of care assays and non-standard comprehensive genomic profiling where available. Concordance will be assessed based on review of laboratory molecular profiling reports by study molecular tumour board.
Timepoint [2] 418345 0
36 months post-enrolment
Secondary outcome [3] 418347 0
Plasma ctDNA turn-around time to result in days (compared to standard of care molecular and tissue next generation sequencing if available) for an Asia Pacific population sequenced abroad. Turn around time is defined as date/time of sample collection to date/time of report availability, and will be collected from audit of pathology reports.
Timepoint [3] 418347 0
36 months post-enrolment
Secondary outcome [4] 418349 0
Identification of molecular sub-groups of interest determined by ctDNA profiling of blood samples. *Biomarker exploration
Timepoint [4] 418349 0
36 months post-enrolment

Eligibility
Key inclusion criteria
Arm A: advanced ALK+ patients, treatment naïve planned to start lorlatinib
Arm B: advanced ALK+ patients, pre-treated at resistance to any prior ALK directed line of treatment

DYNAMALK is an AURORA sub-study with participation requiring enrolment in AURORA. All existing AURORA participants will be screened for DYNAMALK eligibility and offered participation. Non-AURORA patients can be enrolled into AURORA by their treating clinician specifically to participate in DYNAMALK.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Diagnosis other than ALK+ NSCLC

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
Participants will be recruited over 16 months and followed for 36 months to enable timely reporting respective to the expected survival of ALK+ NSCLC. An interim analysis will be performed and reported at 24 months from study initiation. The treatment naïve and pre-treated cohorts will also be reported on separately. Descriptive statistics will be used. Where relevant, survival analyses and appropriate statistical modelling will be undertaken to evaluate the prognostic predictive role of selected ctDNA markers or profiles, by outcomes observed in the study and by outcomes expected, based on landmark data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2023
Actual
Date of last participant enrolment
Anticipated
30/08/2024
Actual
Date of last data collection
Anticipated
30/08/2027
Actual
Sample size
Target
55
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,WA,VIC
Recruitment hospital [1] 23982 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 23983 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 23984 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 23985 0
Blacktown Hospital - Blacktown
Recruitment hospital [5] 23987 0
Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [6] 23988 0
Concord Private Hospital - Concord
Recruitment hospital [7] 23989 0
Epworth Richmond - Richmond
Recruitment hospital [8] 23990 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [9] 23991 0
GenesisCare - St Leonards - St Leonards
Recruitment hospital [10] 23994 0
Monash Medical Centre - Moorabbin campus - East Bentleigh
Recruitment hospital [11] 23995 0
Northern Beaches Hospital - Frenchs Forest
Recruitment hospital [12] 23996 0
The Prince Charles Hospital - Chermside
Recruitment hospital [13] 23997 0
Royal Hobart Hospital - Hobart
Recruitment hospital [14] 23998 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [15] 23999 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [16] 24000 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [17] 24001 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [18] 24002 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 39488 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 39475 0
2050 - Camperdown
Recruitment postcode(s) [3] 39470 0
2065 - St Leonards
Recruitment postcode(s) [4] 39482 0
2086 - Frenchs Forest
Recruitment postcode(s) [5] 39476 0
2137 - Concord
Recruitment postcode(s) [6] 39489 0
2145 - Westmead
Recruitment postcode(s) [7] 39473 0
2148 - Blacktown
Recruitment postcode(s) [8] 39471 0
3000 - Melbourne
Recruitment postcode(s) [9] 39487 0
3065 - Fitzroy
Recruitment postcode(s) [10] 39472 0
3084 - Heidelberg
Recruitment postcode(s) [11] 39477 0
3121 - Richmond
Recruitment postcode(s) [12] 39481 0
3165 - East Bentleigh
Recruitment postcode(s) [13] 39483 0
4032 - Chermside
Recruitment postcode(s) [14] 39486 0
6008 - Subiaco
Recruitment postcode(s) [15] 39485 0
6009 - Nedlands
Recruitment postcode(s) [16] 39478 0
6150 - Murdoch
Recruitment postcode(s) [17] 39484 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 313167 0
Commercial sector/Industry
Name [1] 313167 0
Pfizer Australia
Country [1] 313167 0
Australia
Funding source category [2] 313176 0
Commercial sector/Industry
Name [2] 313176 0
Guardant Health AMEA
Country [2] 313176 0
United States of America
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street Melbourne Victoria 3000 Australia
Country
Australia
Secondary sponsor category [1] 314873 0
None
Name [1] 314873 0
none
Address [1] 314873 0
none
Country [1] 314873 0
Other collaborator category [1] 282550 0
Other Collaborative groups
Name [1] 282550 0
Thoracic Oncology Group Australasia (TOGA)
Address [1] 282550 0
PO Box 1103 Thornbury VIC 3071
Country [1] 282550 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312408 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 312408 0
305 Grattan Street Melbourne Victoria 3000
Ethics committee country [1] 312408 0
Australia
Date submitted for ethics approval [1] 312408 0
24/04/2023
Approval date [1] 312408 0
11/05/2023
Ethics approval number [1] 312408 0

Summary
Brief summary
This study aims to use specialised blood tests to assess any changes in of the tumour DNA circulating in the blood of patients with advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC) throughout their diagnosis and treatment to help improve outcomes.

Who is it for?
You may be eligible for this study if you are an adult aged 18 years or older and you have been diagnosed with advanced ALK+ non-small cell lung cancer. Patients commencing but who have not started treatment with a new ALK-targeted tablet therapy may be eligible to participate in this study. This study is being conducted through the Australian Registry and Biobank of Thoracic Cancers (AURORA). Existing and new AURORA participants will be screened for eligibility and offered participation. Non-AURORA patients can be enrolled into AURORA through a referral by their treating clinician to an AURORA site specifically to participate in this study. Patients receiving treatment at a site not registered with AURORA will still receive their treatment at their local Center, whilst undergoing DYNAMALK activities through the AURORA site which may occur in person or virtually as appropriate.

Study details
All who choose to participate in this study will be asked to provide blood samples at three occasions over a 2 year period, once after they have enrolled, once at 6-12 weeks after enrolment and once again at 2 years after enrolment, or at any earlier time if they have evidence that their cancer has progressed and the current treatment is recommended to stop to consider a new approach.

Tissue samples will be collected where biopsies are performed as part of standard care. Collection of these samples will be organised to coincide with participants' scheduled appointments with their oncologist to minimise the need for additional travel requirements.

Participants who choose to enrol in this study will also be asked to allow the research team to review their previous medical history relevant to their NSCLC diagnosis and treatment. Results from the blood assessments will be provided to participants by their treating clinician within a few weeks after collection and may help their treating clinician to decide on the best treatment strategy.

It is hoped this research will identify how markers from DNA in the blood could be used to understand more confidently how well a treatment will work for patients with ALK+ NSCLC and identify markers that could be used to guide new therapies that will treat these cancers more precisely.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124554 0
Dr Malinda Itchins
Address 124554 0
Royal North Shore Hospital
Reserve Rd, St Leonards NSW 2065
Country 124554 0
Australia
Phone 124554 0
+61 2 9463 1172
Fax 124554 0
Email 124554 0
malinda.itchins@sydney.edu.au
Contact person for public queries
Name 124555 0
Dr Marliese Alexander
Address 124555 0
Peter MacCallum Cancer Centre
305 Grattan Street Melbourne VIC 3000
Country 124555 0
Australia
Phone 124555 0
+61 3 8559 6137
Fax 124555 0
Email 124555 0
Marliese.Alexander@petermac.org
Contact person for scientific queries
Name 124556 0
Dr Marliese Alexander
Address 124556 0
Peter MacCallum Cancer Centre
305 Grattan Street Melbourne VIC 3000
Country 124556 0
Australia
Phone 124556 0
+61 3 8559 6137
Fax 124556 0
Email 124556 0
Marliese.Alexander@petermac.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification; and approval by the trial steering committee.
When will data be available (start and end dates)?
Data will be made immediately following publication with no end date determined.
Available to whom?
Researchers who provide a methodologically sound proposal, case-by-case basis at the discretion of Primary Sponsor and Trial Steering Committee.
Available for what types of analyses?
Only to achieve the aims in the approved proposal, or for IPD meta-analyses, etc.
How or where can data be obtained?
Access subject to approvals by Primary Sponsor and Trial Steering Committee available via AURORA@petermac.org


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18305Study protocol    Study protocol can accessed subject to approvals b... [More Details]



Results publications and other study-related documents

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