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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02645149
Ethics application status
Date submitted
27/12/2015
Date registered
1/01/2016
Date last updated
21/05/2020

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

Other: Standard therapy or clinical trial - Patients with BRAF and NRAS wild type tumour for whom there is no actionable genetic aberration in tumour tissue. These patients will receive trametinib based upon the known MAPK excess activity in the majority of melanomas that may be inhibited by a MEK inhibitor.

Other: Matched targeted therapy - Patients with BRAF and NRAS wild type tumour for whom there is a targeted therapy available, will receive targeted drug matched to gene defect in tumour. 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 these patients will be treated per standard therapy / clinical trial arm.

Other: Trametinib and / or supportive care - Patients with BRAF V600 and NRAS mutations will be treated with standard approved therapies or on clinical trials, and will be followed for clinical response and survival outcomes.


Treatment: Drugs: Standard therapy or clinical trial
Patients with BRAF V600 and NRAS 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 BRAF and NRAS wild type will have tumour tested further using the extended molecular testing platform designed for this project. Patients will first receive standard therapy(ies) for BRAF / NRAS wild type melanoma until disease progression or intolerable drug toxicities. Followed by a targeted therapy matched to the genetic aberration detected in their tumour as listed above.

Treatment: Drugs: Trametinib and / or supportive care
Patients with BRAF and NRAS wild type tumour for whom there is no actionable genetic aberration in tumour tissue following extended molecular testing, may receive trametinib (if not already administered as part of standard care) and/or supportive care.

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 - Genetic aberrations detected by extended molecular profiling in patients with 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 - Patients able to receive matched targeted therapy as a result of genetic aberrations detected with extended molecular profiling, from a pool of all BRAF / NRAS wild type patients.
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 - From consecutive patients with metastatic melanoma tested for common BRAF / NRAS mutations as part of standard care.
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. - Proportion of patients who received matched targeted therapy as a result of genetic aberrations detected with extended molecular profiling who had a 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 - For patients experiencing a complete or partial response to study treatment, the amount of time from this outcome to the time that disease progression or death occurs
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 - The period of time from study entry to progression of disease or death
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 - The proportion of patients alive from the time of study entry
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 - Identify genetic predictors of response and progression using the extended molecular testing platform.
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. - Identify clinicopathological correlates (e.g. age at diagnosis, site of primary tumour, chronic sun damaged skin etc.) of molecular subtypes of melanoma at baseline.
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. - Identify the differences in disease behaviour (e.g. site of metastases, nodular or superficial spreading disease) based on molecular subtypes of melanoma.
Timepoint [8] 0 0
At baseline
Secondary outcome [9] 0 0
Adverse events in patients receiving matched targeted therapy. - Characterisation of adverse events by type, frequency and severity using CTCAE version 5.0
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.

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).

5. Standard of care molecular tumour testing which has identified BRAF / NRAS wild type
tumour tissue.

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. ECOG status 0 - 2.

9. 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).

10. Life expectancy > 30 days.

11. Women of child bearing potential (WOCBP) to use contraception to avoid pregnancy.

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

13. Drug specific inclusions.
Minimum age
18 Years
Maximum age
100 Years
Gender
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).

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.

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
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
2065 - Wollstonecraft

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma Institute Australia
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02645149
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
Maria Gonzalez
Address 0 0
Country 0 0
Phone 0 0
612 9911 7200
Fax 0 0
Email 0 0
maria.gonzalez@melanoma.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02645149