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Trial registered on ANZCTR


Trial ID
ACTRN12616000908437
Ethics application status
Approved
Date submitted
23/05/2016
Date registered
8/07/2016
Date last updated
8/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The Cancer Molecular Screening and Therapeutics (MoST) Program-Screening
Scientific title
The Cancer Molecular Screening and Therapeutics (MoST) Program - A framework protocol for multiple, parallel, signal-seeking clinical studies of novel molecularly targeted therapies for patients with advanced cancer and unmet clinical need.
Secondary ID [1] 289299 0
Nil known
Universal Trial Number (UTN)
U1111-1182-6652
Trial acronym
MoST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 298691 0
Condition category
Condition code
Cancer 298746 298746 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Molecular screening for actionable biomarkers to be used to guide therapy.
Hospital archival tumour tissue will be collected for molecular screening after participant consent and assessment of suitability for the study.

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. 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. Options for treatment as a result of the screening will fall into 3 categories:

1. A MoST program clinical trial
2.A clinical trial outside of the program
3. Other treatments outside of the MoST program at the discretion of the participant's clinician

All participants, including those with no ‘actionable’ biomarkers, will be informed of the results of the screening of their tumour tissue through their clinician.
Intervention code [1] 294686 0
Early detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298228 0
To evaluate a mechanism for screening patients for actionable biomarkers used to guide therapy by measuring a combination of factors (identified individually as secondary outcomes)



Timepoint [1] 298228 0
For the duration of the study. estimated at 4 years. The outcomes will be reviewed regularly and at least annually.
Secondary outcome [1] 325496 0
1. the number of actionable molecular biomarkers identified in screened patients;

Timepoint [1] 325496 0
For the duration of the study. Estimated at 4 years
Secondary outcome [2] 325497 0
2. the number of patients whose therapy is altered on the basis of molecular screening and type of intervention (existing therapy/other trial/MoST substudy);
Timepoint [2] 325497 0
For the duration of the study. Estimated at 4 years
Secondary outcome [3] 325498 0
3. the number of patients enrolled into screening over defined periods;
Timepoint [3] 325498 0
For the duration of the study. Estimated at 4 years
Secondary outcome [4] 325499 0
4. the number of patients eligible for enrolment onto one or more MoST substudy and the number of patients registered onto each substudy;
Timepoint [4] 325499 0
For the duration of the study. Estimated at 4 years
Secondary outcome [5] 325500 0
5. the time taken from patient consenting to communication of screening results to patient;
Timepoint [5] 325500 0
For the duration of the study. Estimated at 4 years
Secondary outcome [6] 325501 0
6. the time taken from identification of an actionable mutation by the MTB (defined as the date of the MTB report) to registration of patient into substudy;
Timepoint [6] 325501 0
For the duration of the study. Estimated at 4 years
Secondary outcome [7] 325502 0
7. a qualitative and quantitative analysis of the molecular screening assays, including sequencing failure rate, costs per genotype screened;
Timepoint [7] 325502 0
For the duration of the study. Estimated at 4 years
Secondary outcome [8] 325503 0
8. the overall survival of patients whose treatment was altered as a result of molecular profiling (either on MoST, via another trial, or other mechanism) compared to those who received standard therapy;
Timepoint [8] 325503 0
For the duration of the study. Estimated at 4 years
Secondary outcome [9] 325504 0
9. a qualitative analysis of patient expectations of the genomic screening and observed clinical outcomes (as reported by questionnaire specifically designed for this study).
Timepoint [9] 325504 0
For the duration of the study. Estimated at 4 years
Secondary outcome [10] 325505 0
To evaluate the composite outcomes of feasibility, efficiency and utility of an overarching framework protocol for multiple, parallel signal-seeking clinical substudies by measuring:

the time from concept proposal to opening of MoST substudy;
the time from ethics approval of MoST program to opening of the first substudy
the time from ethics approval of the addenda to opening of substudies
the number of MoST substudies which yield a positive signal of activity and proceed to formal phase II testing
the number of biomarkers of response identified
timelines to meet key milestones including time taken from: concept proposal to submission of substudy addendum as amendment ethics; amendment submission to ethics approval; ethics approval to substudy opening; substudy opening to completion of enrolment; completion of enrolment to study closure; study closure to reporting of results.
Timepoint [10] 325505 0
For the duration of the study. Estimated at 4 years

Eligibility
Key inclusion criteria
1. Male or female patients, aged 18 years and older, with pathologically confirmed advanced and/or metastatic solid cancer of any histologic type or an earlier diagnosis of a poor prognosis cancer;
2. Sufficient and accessible tissue for molecular screening;
3. Received and failed all standard anticancer therapy (where standard therapy exists) or have documented unsuitability for any further standard anticancer therapy – with the exception of current therapy patient is receiving. It is the intention to screen patients whilst they are receiving the last line of planned standard therapy.
a. Failure is defined as either progression of disease (clinical or radiological) or intolerance to standard therapy resulting in the discontinuation of the therapy.
b. Documented unsuitability for further standard therapy includes known hypersensitivity, organ dysfunction or other patient factors that would make therapy unsuitable in the judgement of the responsible investigator;
4. ECOG performance status 0, 1 or 2;
5. Willing and potentially able to comply with study requirements, including treatment, timing and/or nature of required assessments; It is the intention to screen patients who are in principle wishing to take part 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;
6. Signed, written informed consent to participation in the molecular screening
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Suitable for standard therapy or accepted standard care, if the patient has not been previously treated;
2. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may contraindicate participation and/or interact with the investigational product(s);
3. Other co-morbidities 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. For non central nervous system (CNS) cancers, patients with symptomatic CNS involvement of his/her cancer, unless the subject has stable neurological function without evidence of CNS progression within 12 weeks prior to study entry and does not require treatment with enzyme-inducing anticonvulsants or steroids (within 4 weeks prior to substudy inclusion and during substudy participation);
5. Administration of any non-oncologic investigational treatment within 30 days or 5 half-lives (whichever is longer) prior to receiving the first dose of study treatment;
6. History of another malignancy within 2 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible;
7. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a barrier method of contraception (double barrier, if required).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
NA
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
NA
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
This framework protocol provides a structure to screen patients for actionable molecular biomarkers to guide treatment.

Patients will be eligible for treatment in substudies based on the expression of actionable mutations or other molecular biomarkers in their tumours. For some treatments, where predictive biomarkers are not well characterised or thresholds are unknown, a post-hoc analysis will be performed to identify biomarkers.


Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Sample size
1000 patients will be recruited for screening to identify actionable mutations and eligibility for enrolment into MoST substudies.

The sample set of 1000 was chosen to allow for finding one of around 300 mutations (at various frequencies) and allow for the treatment of 192 patients on 12 individual substudies.

This protocol provides a framework to conduct molecular screening of patients and the development and implementation of multiple, parallel, early-phase, signal-seeking substudy trials. It is planned that 12 substudy modules will be opened during the first 4 years of the study. Each substudy will enrol 16 patients. A primarily descriptive analysis will be used to evaluate the feasibility, efficiency, utility and costs of the framework protocol, with data about the development and conduct of each substudy contributing to this analysis. Data about unsuccessful substudies (ie trial concepts that do not progress to a substudy within the MoST program) will also be collected to inform the evaluation of the framework.



Recruitment
Recruitment status
Not yet 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
Recruitment hospital [1] 5755 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 5756 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 13225 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 13226 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 293552 0
Government body
Name [1] 293552 0
Office for Health and Medical Research
Address [1] 293552 0
Locked Mail Bag 961
North Sydney NSW 2059
Country [1] 293552 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] 292366 0
None
Name [1] 292366 0
Address [1] 292366 0
Country [1] 292366 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294991 0
St Vincent's Hospital Sydney Human Research Ethics Committee
Ethics committee address [1] 294991 0
390 Victoria Street
Darlinghurst NSW 2010
Ethics committee country [1] 294991 0
Australia
Date submitted for ethics approval [1] 294991 0
01/02/2016
Approval date [1] 294991 0
01/04/2016
Ethics approval number [1] 294991 0
HREC/16/SVH/23

Summary
Brief summary
This study aims to screen patients with advanced cancer and unmet clinical needs for actionable biomarkers to be used to guide therapy.
Who is it for? You may be eligible to join this study if you are aged 18 years and older, with pathologically confirmed advanced and/or metastatic solid cancer of any cell type or an earlier diagnosis of a poor prognosis cancer and have received all standard anticancer therapy.
Study details: A small part of your tumour tissue, which was collected from a previous biopsy or surgery, will be used to identify a biomarker by doing a laboratory analysis (‘molecular screening’). The screening includes genetic panel testing, which means looking for changes in a subset of genes (DNA) in your tumour tissue and other laboratory assays. 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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65698 0
Prof David Thomas
Address 65698 0
Garvan Institute of Medical Research
The Kinghorn Cancer Centre, 370 Victoria Street
Darlinghurst NSW 2010

Country 65698 0
Australia
Phone 65698 0
+612 9355 5770
Fax 65698 0
+612 9355 5872
Email 65698 0
d.thomas@garvan.org.au
Contact person for public queries
Name 65699 0
Dr Lucille Sebastian
Address 65699 0
NHMRC Clinical Trials Centre
Level 6, Chris O'Brien Lifehouse
119–143 Missenden Road, Camperdown NSW 2050
Country 65699 0
Australia
Phone 65699 0
+61295625000
Fax 65699 0
Email 65699 0
most@ctc.usyd.edu.au
Contact person for scientific queries
Name 65700 0
Prof David Thomas
Address 65700 0
Garvan Institute of Medical Research
The Kinghorn Cancer Centre, 370 Victoria Street
Darlinghurst NSW 2010
Country 65700 0
Australia
Phone 65700 0
+612 9355 5770
Fax 65700 0
+612 9355 5872
Email 65700 0
d.thomas@garvan.org.au