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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02645149




Registration number
NCT02645149
Ethics application status
Date submitted
27/12/2015
Date registered
1/01/2016

Titles & IDs
Public title
Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma
Scientific title
Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma
Secondary ID [1] 0 0
MIA2015/174
Universal Trial Number (UTN)
Trial acronym
MatchMel
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Standard therapy or clinical trial
Treatment: Drugs - Matched targeted therapy
Treatment: Drugs - Trametinib and / or supportive care
Treatment: Drugs - CDK4/6 and MEK inhibitor
Treatment: Drugs - Compassionate Access Targeted Therapy

Experimental: A1. Non-V600 BRAF, BRAF wildtype, NRAS wildtype. Actionable gene mutation, matched drug available - Patients will receive targeted drug matched to the actionable gene mutation detected on NGS testing. If a patient cannot receive the matched targeted therapy because of the existence of one or more drug specific exclusion criteria, an alternative matched therapy may be assigned, or trametinib, or clinical trials if available.

Experimental: A2. Non-V600 BRAF, BRAF wildtype, NRAS wildtype. Actionable gene mutation, no matched drug available - Patients may have an actionable aberration for which there is no current study-specific drug supply available. In this scenario, access will be sought for compassionate use of the relevant approved targeted therapy.

Experimental: A3. Non-V600 BRAF, BRAF wild type and NRAS wild type melanoma - no actionable genetic aberration - Patients for whom there is no actionable genetic aberration will receive trametinib, based upon the known MAPK excess activity in the majority of melanomas that may be inhibited by a MEK inhibitor

Experimental: B. Mucosal melanoma - Patients will receive combined trametinib and ribociclib based on evidence to suggest that combined MEK inhibition and CDK4/6 inhibition may be effective. After failure of trametinib and ribociclib, actionable genetic aberrations from the NGS testing will be reviewed for the opportunity to use a further targeted therapy off label.

Experimental: C. NRAS mutant melanoma - Patients with an NRAS mutation detected on standard gene testing only will receive combined trametinib and ribociclib based on evidence that combining MEK inhibition and CDK4/6 inhibition is a viable treatment option.

Other: D. BRAF V600 mutant melanoma - Patients will receive standard of care treatment only.


Treatment: Drugs: Standard therapy or clinical trial
Patients with BRAF V600 mutations detected by standard of care tumour testing will be treated with standard approved therapies or on clinical trials.

Treatment: Drugs: Matched targeted therapy
Patients with tumour found to be non-V600 BRAF, BRAF wildtype and NRAS wildtype melanoma will have tumour tested further using the extended molecular testing platform designed for this project. Patients will first receive standard therapy(ies) for non-V600 BRAF, wildtype and NRAS wildtype melanoma until disease progression or intolerable drug toxicities. Followed by a targeted therapy matched to the genetic aberration detected in their tumour on NGS testing.

Treatment: Drugs: Trametinib and / or supportive care
Patients with non-V600 BRAF, BRAF wildtype and NRAS wildtype melanoma for whom there is no actionable genetic aberration found on extended molecular testing, may receive trametinib (if not already administered as part of standard care) and/or supportive care.

Treatment: Drugs: CDK4/6 and MEK inhibitor
Patients mucosal melanoma and any genetic aberration on NGS testing may receive ribociclib + trametinib initially. After failure of trametinib and ribociclib, actionable genetic aberrations from the NGS testing will be reviewed for the opportunity to use a further targeted therapy off label.

Patients with an NRAS mutation on standard of care tumour testing will also receive ribociclib + trametinib.

Treatment: Drugs: Compassionate Access Targeted Therapy
Patients with non-V600 BRAF, BRAF wildtype and NRAS wildtype melanoma may have an actionable aberration(s) for which there is no current study-specific drug supply. In this scenario, access will be sought for compassionate use of the off label use of the relevant regulatory approved targeted therapy
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Type and frequency of genetic aberrations in BRAF/NRAS wild-type metastatic melanoma
Timepoint [1] 0 0
For the duration of the study, estimated at 5 years.
Primary outcome [2] 0 0
Proportion of patients with BRAS/NRAS wild-type melanoma receiving targeted therapy
Timepoint [2] 0 0
For the duration of the study, estimated at 5 years.
Secondary outcome [1] 0 0
Proportion of patients who have BRAF/NRAS wild type melanoma
Timepoint [1] 0 0
For the duration of the study, estimated at 5 years.
Secondary outcome [2] 0 0
Proportion of patients with complete (CR) or partial (PR) response.
Timepoint [2] 0 0
From date of targeted therapy commencement until the date of first documented objective partial or complete response per RECIST, assessed up to 60 months.
Secondary outcome [3] 0 0
Duration of response
Timepoint [3] 0 0
From date of first objective partial or complete response to disease progression or death, which ever is sooner, assessed up to 60 months.
Secondary outcome [4] 0 0
Progression free survival
Timepoint [4] 0 0
From date of targeted therapy commencement to date of objective disease progression per RECIST, assessed up to 60 months.
Secondary outcome [5] 0 0
Overall survival
Timepoint [5] 0 0
From date of targeted therapy commencement to date of death from any cause, assessed up to 60 months.
Secondary outcome [6] 0 0
Correlation of genetic aberration detected in tumour tissue with clinical response and disease progression
Timepoint [6] 0 0
From date of targeted therapy commencement to date of to partial or complete response or disease progression, assessed up to 60 months.
Secondary outcome [7] 0 0
Correlation of with genetic aberration detected in tumour tissue with age at diagnosis, site of primary tumour, chronic sun damaged skin.
Timepoint [7] 0 0
At baseline
Secondary outcome [8] 0 0
Correlation of genetic aberration detected in tumour tissue with site of metastases, nodular or superficial spreading disease.
Timepoint [8] 0 0
At baseline
Secondary outcome [9] 0 0
Adverse events in patients receiving matched targeted therapy.
Timepoint [9] 0 0
From date of the start of targeted therapy to 30 days from discontinuation of targeted therapy

Eligibility
Key inclusion criteria
Inclusion criteria for Inclusion in Molecular Testing Platform:

1. Newly diagnosed and treatment naïve unresectable Stage IIIB, IIIC or Stage IV melanoma (including sub types: cutaneous, mucosal, acral, ungual, uveal and unknown primary).
2. Archival metastatic tumour tissue available for genetic testing. Archival tissue from primary melanoma may be considered if no recent sample is available.
3. Male or female patients aged 18 or over.
4. Written informed consent for molecular genetic testing of tumour tissue (for both standard and research tests).

Inclusion Criteria for Matched Targeted Therapy:

6. Received available standard therapies for metastatic melanoma and progressed, unable to tolerate standard therapy, or standard therapy contraindicated.

7. Written informed consent to receive targeted therapy (if applicable) and clinical follow up.

8. Patient has an 'actionable' genetic aberration and matched targeted therapy is available. Patients with no genetic aberration or where no matched targeted therapy is available, patients will be offered trametinib 9. ECOG status 0 - 2. 10. Adequate haematological, hepatic and renal organ function as defined by:

1. White cell count = 2.0 × 109/L
2. Neutrophil count = 1.5 × 109/L
3. Haemoglobin = 90 g/L
4. Platelet count = 100 x 109/L
5. Total bilirubin = 3.0 x ULN
6. Alanine transaminase = 3.0 x ULN
7. Aspartate aminotransferase = 3.0 x ULN
8. Serum creatinine = 1.5 x the upper limit of normal (ULN). 11. Life expectancy > 30 days. 12. Women of child bearing potential (WOCBP) to use contraception to avoid pregnancy.

13. Non sterile men with female partners of CBP to use contraception to avoid pregnancy.

14. Drug specific inclusions.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for Matched Targeted Therapy:
1. An expectation for the need for concurrent radiotherapy (unless safety has been established with the matched drug regimen and is directed at one anatomical region for symptom control).
2. Any investigational drug or other systemic drug therapy for melanoma within 14 days or 5 half-lives from baseline, whichever is shorter.
3. Pregnant or breast feeding females.
4. Drug specific exclusions.
5. Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug

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
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2028
Actual
Sample size
Target
1000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
2260 - Wollstonecraft

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma Institute Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Novartis
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alex Menzies
Address 0 0
Melanoma Institute Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Monica Osorio
Address 0 0
Country 0 0
Phone 0 0
612 9911 7296
Fax 0 0
Email 0 0
monica.osorio@melanoma.org.au
Contact person for scientific queries

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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02645149