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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01972347




Registration number
NCT01972347
Ethics application status
Date submitted
17/06/2013
Date registered
30/10/2013
Date last updated
30/08/2023

Titles & IDs
Public title
Neoadjuvant Dabrafenib + Trametinib for AJCC Stage IIIB-C BRAF V600 Mutation Positive Melanoma
Scientific title
An Open Label, Single Centre, Phase II Pilot Study of Neoadjuvant Dabrafenib + Trametinib in Patients With Resectable American Joint Committee on Cancer (AJCC) Stage IIIB-C BRAF V600 Mutation Positive Melanoma
Secondary ID [1] 0 0
200332
Universal Trial Number (UTN)
Trial acronym
Neo Combi
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 - Dabrafenib
Treatment: Drugs - Trametinib

Experimental: Dabrafenib and Trametinib - Dabrafenib 150mg bid orally and Trametinib 2mg od orally for 52 weeks


Treatment: Drugs: Dabrafenib
Patients will receive neoadjuvant treatment with dabrafenib 150mg twice a day and trametinib 2mg once a day for 12 weeks. Patients will then have complete lymph node dissection and will continue on maintenance treatment with dabrafenib 150mg twice a day and trametinib 2mg once a day for 40 weeks.

Treatment: Drugs: Trametinib
Patients will receive neoadjuvant treatment with dabrafenib 150mg twice a day and trametinib 2mg once a day for 12 weeks. Patients will then have complete lymph node dissection and will continue on maintainance treatment with dabrafenib 150mg twice a day and trametinib 2mg once a day for 40 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The proportion of viable melanoma tissue, compared to baseline, in dissected lymph node and / or in-transit tumour tissue after 12 weeks of neoadjuvant treatment.
Timepoint [1] 0 0
12 weeks
Secondary outcome [1] 0 0
Effects of neoadjuvant study treatment on surgical outcomes after complete lymph node and / or in-transit disease dissection.
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Effects of study treatment on host immune response in tumour tissue and peripheral blood.
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Correlation of pyrexia episodes and signs with baseline melanoma disease burden (number and size of lymph nodes), RECIST response, pathological response, immune related changes in tumour tissue and peripheral blood.
Timepoint [3] 0 0
52 weeks
Secondary outcome [4] 0 0
Description of specific blood and serum changes that occur with pyrexia.
Timepoint [4] 0 0
52 weeks
Secondary outcome [5] 0 0
Relapse free survival
Timepoint [5] 0 0
52 weeks plus the time when 70% of patients have died
Secondary outcome [6] 0 0
Overall survival
Timepoint [6] 0 0
52 weeks plus until the time that 70% of patients have died
Secondary outcome [7] 0 0
Description of adverse events and how these correlate with clinical outcomes
Timepoint [7] 0 0
52 weeks
Secondary outcome [8] 0 0
The clinical response to 12 weeks neoadjuvant treatment
Timepoint [8] 0 0
12 weeks
Secondary outcome [9] 0 0
Correlation of a range of tumour biomarkers at baseline, early treatment and 12 week intervals with pathological and clinical response.
Timepoint [9] 0 0
12 weeks

Eligibility
Key inclusion criteria
- Age =18 years

- Histologically confirmed AJCC Stage IIIB or IIIC (Tx, T1-4, N1b, N2b, N2c, N3, Mo)
cutaneous melanoma or unknown primary determined to be BRAF V600 mutation positive,
with sufficient nodal or in-transit disease to enable biopsies prior to
surgery.Patients must have disease that is measurable per RECIST version 1.1

- Able to swallow and retain oral medication and must not have any clinically
significant gastrointestinal abnormalities that may alter absorption

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

- Adequate baseline organ function

- Women of childbearing potential must have a negative serum pregnancy test within 7
days of first dose of study treatment and agree to use effective contraception from 14
days prior to commencing study treatment, throughout the treatment period and for 4
months after the last dose of study treatment

- Men with any female partner of childbearing potential must agree to use effective
contraception from 14 days prior to commencing study treatment, throughout the
treatment period and for 4 months after the last dose of study treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known mucosal or ocular melanoma or any unresectable in-transit metastases

- Evidence of distant metastatic disease on screening evaluation

- Prior anti-cancer treatment for melanoma (chemotherapy, immunotherapy, biologic
therapy, vaccine therapy, investigational treatment or radiotherapy). Prior surgery
for melanoma is allowed.

- Taken an investigational drug within 28 days or 5 half-lives, whichever is longer,
prior to commencing study treatment.

- Current or expected use of a prohibited medication(s)

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study treatments, their excipients, and/or dimethyl
sulfoxide (DMSO)

- Known HIV

- A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency

- History of another malignancy or a concurrent malignancy except:

1. Patients who have been disease-free for 3 years and have a life expectancy of > 5
years;

2. Patients with a history of completely resected non-melanoma skin cancer or
successfully treated in situ carcinoma are eligible, for example cervical cancer
in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary
melanomas.

- A history or evidence of cardiovascular risk including any of the following: a. QT
interval corrected for heart rate using the Bazett's formula =480 msec or = 450 msec
for patients with bundle branch block; b. History or evidence of current clinically
significant uncontrolled arrhythmias; c. History of acute coronary syndromes
(including myocardial infarction or unstable angina), coronary angioplasty, or
stenting within 6 months prior to commencement of study treatment; d. History or
evidence of current = Class II congestive heart failure; e. Abnormal cardiac valve
morphology documented by echocardiogram which in the opinion of the investigator could
interfere with the patient's safety.

f. Treatment refractory hypertension defined as a blood pressure of systolic > 140 mm
Hg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive
therapy.

- A history or current evidence/risk of retinal vein occlusion (RVO) or central serous
retinopathy (CSR)

- Any serious or unstable pre-existing medical conditions (aside from the malignancy
exceptions specified above), psychiatric disorders, or other conditions that, in the
opinion of the treating clinician, could interfere with the patient's safety,
obtaining informed consent, or compliance with study procedures.

- Breastfeeding females

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2024
Actual
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Melanoma Institute Australia - North Sydney
Recruitment postcode(s) [1] 0 0
2060 - North Sydney

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

Ethics approval
Ethics application status

Summary
Brief summary
This is an open label, single centre, phase II study of neoadjuvant drug treatment with
dabrafenib + trametinib in patients with resectable American Joint Committee on Cancer (AJCC)
Stage IIIB-C BRAF V600 mutation positive melanoma.

The main aim of this study is to find out if giving of a new combined drug treatment to
patients with melanoma that has spread to the lymph nodes BEFORE they have surgery, will
result in improved clinical and pathological response of the melanoma tissue after 12 weeks
treatment.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01972347
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Georgina Long
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01972347