Eligibility Module
The Eligibility Module contains detailed information about who can participate in the clinical trial. This includes eligibility criteria, age restrictions, gender requirements, healthy volunteer status, and study population descriptions, helping researchers understand who is eligible to participate in the study.
Eligibility Module path is as follows:
Study -> Protocol Section -> Eligibility Module
Eligibility Module
Ignite Creation Date:
2025-12-24 @ 5:31 PM
Ignite Modification Date:
2025-12-24 @ 5:31 PM
NCT ID:
NCT04720768
Eligibility Criteria:
Inclusion Criteria:
Dose Escalation Phase only: (Australia only)
1. Patients who are naïve to, or have received prior BRAF and MEK inhibitor combination therapy. Prior treatment with chemotherapy and biological therapy (e.g. checkpoint inhibitor therapy) is permitted.
Dose Expansion Phase only: (All sites)
2. Cohort 1: Patients who are naïve to BRAF and MEK inhibitor therapy. Prior treatment with chemotherapy and biological therapy (e.g. checkpoint inhibitor therapy) is permitted.
3. Cohort 2: Patients who have progressed on prior BRAF and MEK inhibitor combination therapy. Prior treatment with chemotherapy and biological therapy (e.g. checkpoint inhibitor therapy) is permitted.
For both phases (All sites):
4. Patients (male and female) age ≥ 18 years
5. Has provided written informed consent prior to any screening procedure
6. Histologically confirmed diagnosis of unresectable stage III or IV melanoma (stage IIIB to IV per American Joint Committee on Cancer \[AJCC\] 8th edition).
7. Documented evidence of BRAF V600 mutation.
8. Patients must provide either archival or newly obtained tumour sample at baseline. In addition, patients must agree to a mandatory biopsy during treatment and at the time of progression, if not medically contraindicated.
9. Evidence of measurable disease, as determined by RECIST v1.1. Note: Lesions in areas of prior radiotherapy or other locoregional therapies (e.g., percutaneous ablation) should not be considered measurable, unless lesion progression has been documented since the therapy.
10. Patients must have adequate haematological, coagulation, renal and hepatic functions as defined by:
Absolute neutrophil count ≥ 1.5 x 109/L Haemoglobin ≥ 10 g/L without transfusions Platelet count ≥ 100 x 109/L without transfusions Total serum creatinine ≤ 1.5 x ULN or calculated or directly measured CrCl \< 50% LLN (lower limit of normal) Serum total bilirubin ≤ 1.5 x ULN ( 3 x ULN in cases of known Gilbert's syndrome) AST/SGOT or ALT/SGPT ˂ 3 x ULN, or ˂ 5 x ULN if liver metastases are present PT/INR or aPTT \< 1.5xULN
11. ECOG Performance Status ≤ 2
12. Able to take oral medications
13. Be willing and able to comply with all study requirements, including treatment, attending assessments and follow-up.
14. Female patients of childbearing potential must have a negative serum pregnancy test at screening: and be willing to use two methods of birth control or be surgically sterile: or abstain from heterosexual activity for the course of the study through to 3 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilised or have not been free from menses for \> 1 year.
15. Sexually active males must use a condom during intercourse while taking the study drugs and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomised men in order to prevent delivery of the drug via seminal fluid.
Exclusion Criteria:
1. Patients with uveal melanoma.
2. Patients with symptomatic or untreated brain metastases or leptomeningeal disease. Patients with previously treated or untreated for brain metastasis that are asymptomatic in the absence of corticosteroid therapy or on a stable dose of steroids for 4 weeks prior to registration are allowed to enroll. Brain metastases must be stable at least 4 weeks prior to registration with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases).
3. Patients receiving enzyme inducing anti-epileptic drugs (as listed in Appendix 5).
4. History of acute or chronic pancreatitis.
5. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
6. Impaired cardiovascular function or clinically significant cardiac disease including any of the following:
* CHF requiring treatment (NYHA grade ≥ 2)
* LVEF \< 50% as determined by MUGA scan or ECHO
* History or presence of clinically significant ventricular arrhythmias or uncontrolled atrial fibrillation
* Clinically significant resting bradycardia
* Unstable angina pectoris ≤ 3 months prior to registration
* Acute Myocardial Infarction (AMI) ≤ 3 months prior to registration
* QTcF \> 480 ms
* Any heart disease that requires the use of a cardiac pacemaker or implantable cardioverter defibrillator ≤ 3 months prior to registration
* History of QT syndrome, Brugada syndrome or known
Healthy Volunteers:
False
Sex:
ALL
Minimum Age:
18 Years
Maximum Age:
100 Years
Study:
NCT04720768
Study Brief:
Protocol Section:
NCT04720768