Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001187437
Ethics application status
Approved
Date submitted
22/11/2015
Date registered
29/08/2016
Date last updated
3/10/2019
Date data sharing statement initially provided
3/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Molecular Profiling and Matched Targeted Therapy for Patients with Metastatic Melanoma (MatchMel)
Scientific title
Molecular profiling to identify patients with BRAF/NRAS wild type melanoma and the proportion of these patients that undergo matched targeted therapy as a result of extended molecular testing.
Secondary ID [1] 287957 0
Protocol Number MIA2015/174
Universal Trial Number (UTN)
Trial acronym
MatchMel
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Melanoma 296834 0
Condition category
Condition code
Cancer 297064 297064 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a patient oriented translational research project aiming to improve clinical outcomes for patients with BRAF and NRAS wild-type unresectable Stage III or Stage IV metastatic melanoma who have progressed on, or are unable to receive standard therapy (in general, immunotherapy).

Consecutive patients seen at three major clinics with unresectable Stage III or IV melanoma will be invited to participate. All patients are first provided with the standard care BRAF/NRAS mutation testing, followed by standard care therapy.

Those patients with melanoma found to be BRAF/NRAS wild type will also undergo extended molecular testing of their melanoma. The extended test in this project covers approximately 400 cancer related genes. Following progression on standard therapy, patients with BRAF/NRAS wild type melanoma will be reviewed at a meeting of the project multidisciplinary team. Patients will be offered a targeted therapy matched to the genetic aberrations detected on extended testing. The current library of targeted therapies include:

Everolimus
Bortezomib
Cabozantinib
Ceritinib
Crizotinib
Dasatinib
Erlotinib
Everolimus
Gefitinib
Imatinib
Lapatinib
Nilotinib
Olaparib
Palbociclib
Pazopanib
Ramucirumab
Regorafenib
Sorafenib
Sunitinib
Trametinib
Vorinostat

Where multiple targets are identified in one patient, or where multiple potential therapies would be appropriate for a single tumour mutation, the appropriate therapeutic approach will be decided after consultation with the multidisciplinary team, using the latest version of library of matched therapies. Similarly, for patients where no genetic aberration was detected or for whom there is no current targeted therapy available for a specific genetic aberration, further treatment will be discussed with the molecular multidisciplinary team formed for this project.

All patients who consent to participate in the study will be followed up until death.
Intervention code [1] 293301 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296668 0
Frequency of genetic aberrations in BRAF/NRAS wild-type metastatic melanoma assessed using fresh or archival tumour tissue samples.
Timepoint [1] 296668 0
Assessed following diagnosis of metastatic melanoma.
Primary outcome [2] 296686 0
Proportion of patients with BRAF/NRAS wild type melanoma receiving matched targeted therapy.
Timepoint [2] 296686 0
At end of standard care treatment due to progression or unacceptable toxicities.
Secondary outcome [1] 319077 0
Proportion of patients who have BRAF/NRAS wild type melanoma assessed using fresh or archival tumour tissue samples.
Timepoint [1] 319077 0
Assessed following diagnosis of metastatic melanoma.
Secondary outcome [2] 319078 0
Proportion of patients with complete (CR) or partial (PR) response per RECIST criteria.
Timepoint [2] 319078 0
From start of matched targeted therapy to time of objective partial or complete response per RECIST.
Secondary outcome [3] 319079 0
Duration of response per RECIST criteria.
Timepoint [3] 319079 0
From time of first objective partial or complete response to disease progression or death.
Secondary outcome [4] 319080 0
Time from start of matched therapy(ies) to progression.
Timepoint [4] 319080 0
From start of matched targeted therapy to time of objective progression per RECIST.
Secondary outcome [5] 319081 0
Time from start of matched therapy(ies) to death.
Timepoint [5] 319081 0
From start of matched targeted therapy to time of death from any causes.
Secondary outcome [6] 319082 0
Comparison of overall survival between patients receiving matched targeted therapy to patients receiving standard care only.
Timepoint [6] 319082 0
From start of matched targeted therapy or standard care to time of death from any cause.
Secondary outcome [7] 319083 0
Correlation of genetic aberration assessed using archival or fresh tumour sample with disease response or progression assessed per RECIST criteria.
Timepoint [7] 319083 0
From start of matched targeted therapy to response or progression.
Secondary outcome [8] 319084 0
Correlation of clinicopathological features assessed using a review of hospital records with genetic aberration detected from archival or fresh tumour sample.
Timepoint [8] 319084 0
At baseline, following results from extended molecular testing.
Secondary outcome [9] 319085 0
Correlation of disease behaviour assessed by histology results using archival or fresh tumour sample with genetic aberration detected from archival or fresh tumour sample.
Timepoint [9] 319085 0
At baseline, following results from extended molecular testing.
Secondary outcome [10] 319118 0
Comparison of duration of response per RECIST between patients receiving matched targeted therapy to patients receiving standard care only.
Timepoint [10] 319118 0
From time of first objective partial or complete response to disease progression or death..
Secondary outcome [11] 319119 0
Comparison of progression free duration per RECIST between patients receiving matched targeted therapy to patients receiving standard care only.
Timepoint [11] 319119 0
From start of matched targeted therapy or standard care to disease progression.

Eligibility
Key inclusion criteria
INITIAL INCLUSION CRITERIA:
Newly diagnosed and treatment naive unresectable Stage IIIB, IIIC or Stage IV melanoma.
Archival or fresh metastatic tumour tissue available for genetic testing. Archival tissue from primary melanoma may be considered if no recent sample is available.
Male or female patients aged 18 or over.
Written informed consent for molecular genetic testing of tumour tissue (for both standard and research tests).

INCLUSION CRITERIA FOR EXTENDED MOLECULAR TESTING:
Standard of care molecular tumour testing which has identified BRAF / NRAS wild type tumour tissue.

INCLUSION CRITERIA FOR MATCHED TARGETED THERAPY:
Received available standard therapies for metastatic melanoma and progressed, unable to tolerate standard therapy, or standard therapy contraindicated.
Written informed consent to receive targeted therapy (if applicable) and clinical follow up.
ECOG status 0 - 2.
Adequate haematological, hepatic and renal organ function as defined by:
White cell count = or > 2.0 × 10^9/L
Neutrophil count = or > 1.5 × 10^9/L
Haemoglobin = or > 90 g/L
Platelet count = or >100 x 10^9/L
Total bilirubin < or = 3.0 x ULN
Alanine transaminase < or = 3.0 x ULN
Aspartate aminotransferase < or = 3.0 x ULN
Serum creatinine < or = 1.5 x the upper limit of normal (ULN).
Life expectancy > 30 days.
Women of child bearing potential (WOCBP) to use contraception to avoid pregnancy.
Non sterile men with female partners of CBP to use contraception to avoid pregnancy.
Drug specific inclusions (refer to the regulatory approved drug specific Product Information provided)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
EXCLUSION CRITERIA FOR MATCHED TARGETED THERAPY:
An expectation for the need for concurrent radiotherapy (unless safety has been established with the matched drug regimen).
Any investigational drug or other systemic drug therapy for melanoma within 14 days or 5 half-lives from baseline, whichever is shorter.
Pregnant or breast feeding females.
Drug specific exclusions (refer to the regulatory approved drug specific Product Information Sheet provided)

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)
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
Other
Other design features
This is a patient oriented translational research project aiming to improve clinical outcomes for patients with BRAF and NRAS wild-type unresectable Stage III or Stage IV metastatic melanoma who have progressed on, or are unable to receive standard therapy (in general, immunotherapy). Consecutive patients seen at three major clinics and fitting the broad eligibility criteria will be invited to participate.

The approach is designed to test the impact of different targeted drugs on different mutations in a single type of cancer. In this project, patients will have tumour tissue genetically profiled to determine which mutation(s) are present, and will then be assigned to receive a matched drug expected to target the mutation(s) in the tumour. Where multiple targets are identified in one patient, or where multiple potential therapies would be appropriate for a single tumour mutation, the treating clinician may determine the appropriate therapeutic approach after consultation with the study team, using the latest version of library of matched therapies.
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2019
Actual
Date of last participant enrolment
Anticipated
1/01/2023
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
1000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 4699 0
The Poche Centre, Melanoma Institute Australia - North Sydney
Recruitment hospital [2] 4700 0
Westmead Hospital - Westmead
Recruitment hospital [3] 4701 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 12271 0
2065 - Wollstonecraft
Recruitment postcode(s) [2] 12272 0
2145 - Westmead
Recruitment postcode(s) [3] 12273 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 292431 0
Charities/Societies/Foundations
Name [1] 292431 0
Melanoma Institute Australia
Country [1] 292431 0
Australia
Funding source category [2] 292432 0
Government body
Name [2] 292432 0
National Health and Medical Research Council
Country [2] 292432 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Melanoma Institute Australia
Address
The Poche Centre
40 Rocklands Road
Wollstonecraft
NSW 2065
Country
Australia
Secondary sponsor category [1] 291126 0
None
Name [1] 291126 0
None
Address [1] 291126 0
None
Country [1] 291126 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293892 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 293892 0
Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 293892 0
Australia
Date submitted for ethics approval [1] 293892 0
12/10/2015
Approval date [1] 293892 0
21/04/2016
Ethics approval number [1] 293892 0
HREC/15/RPAH/501

Summary
Brief summary
The primary purpose of this study is to evaluate the efficacy of cancer therapy which is matched specifically to the genetic profile of each individual's tumour in patients with metastatic melanoma.
Who is it for? You may be eligible to participate in this study if you are aged 18 or over, and are newly diagnosed with stage IIIB, IIIC or IV melanoma.
Study details: All participants in this study will first undergo standard testing to establish whether a certain type of genetic mutation (BRAF/NRAS mutation) is present in their tumour cells. This is carried out using an existing or fresh tumour tissue sample. All participants will then begin standard care therapy for the melanoma. In participants with tumours testing negative for BRAF/NRAS mutations in the initial test, and who show disease progression or who are unable to continue standard care therapy, further testing on their tumour tissue sample will be carried out. This will provide further information regarding the genetic profile of the tumour. Researchers will then match this genetic profile to a specific therapy which targets it. Researchers will measure disease progression and survival to evaluate the efficacy of the matched targeted treatment in comparison to standard care only. The matched targeted therapies which may be used will be continuously updated as other research provides more information on which drugs may target which genetic profiles. It is hoped that the findings of this study will provide valuable information regarding the efficacy of therapies which target the specific genetic profile of metastatic melanoma tumours, in comparison to the current standard care.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 61706 0
Dr Alexander Menzies
Address 61706 0
Melanoma Institute Australia
The Poche Centre
40 Rocklands Road
Wollstonecraft NSW 2065
Country 61706 0
Australia
Phone 61706 0
+612 9911 7200
Fax 61706 0
Email 61706 0
[email protected]
Contact person for public queries
Name 61707 0
Maria Gonzalez
Address 61707 0
Melanoma Institute Australia
The Poche Centre
40 Rocklands Road
Wollstonecraft NSW 2065
Country 61707 0
Australia
Phone 61707 0
+612 9911 7311
Fax 61707 0
Email 61707 0
[email protected]
Contact person for scientific queries
Name 61708 0
Alexander Menzies
Address 61708 0
Melanoma Institute Australia
The Poche Centre
40 Rocklands Road
Wollstonecraft NSW 2065
Country 61708 0
Australia
Phone 61708 0
+612 9911 7311
Fax 61708 0
Email 61708 0
[email protected]

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


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.