Melanoma
Conditions
Keywords
Melanoma, NRAS
Brief summary
This is a phase I/II, open-label, dose escalation study to evaluate tolerability, safety, pharmacokinetics and efficacy in patients with NRAS mutant advanced melanoma .
Interventions
DRUGHL-085
HL-085 is one MEK inhibitor.
Sponsors
Shanghai Kechow Pharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma according to AJCC (Version 7, 2010). 2. Subjects must have NRAS mutation in melanoma. 3. Chemotherapy, immunotherapy or radiotherapy ≥ 4 weeks prior to starting the study treatment. Surgery (except for tumor biopsy) or severe trauma ≤ 14 days prior to starting the study treatment. 4. ECOG performance status of 0-1. 5. Life expectancy ≥ 3 months. 6. Ability to take the medicine orally. 7. Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
1. Prior therapy with a MEK-inhibitor 2. Patients with known hypersensitivity to study drug ingredients or their analogues. 3. Active central nervous system (CNS) lesion. 4. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome. 5. Subjects with bleeding symptoms at Grade 3 (NCI-CTCAE v4.03) within 4 weeks prior to starting study treatment. 6. Uncontrolled concomitant diseases or infectious diseases. 7. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.). 8. History of HIV,HCV,HBV infection. 9. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded. 10. Serum HCG test is positive. 11. Other conditions that influence the results and increase the risk of study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events | Duration of the study, estimated to be approximately 24 months. | Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 during the study period |
| Maximum tolerated dose (MTD) | DLTs within the first cycle of therapy (up to 35 days) | The dose level immediately below the dose level at which ≥ 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity (DLT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) | Duration of the study, estimated to be approximately 24 months | Cmax of HL-085 following single and repeated dosing |
| Objective Response Rate (ORR) as measure of efficacy | Duration of the study, estimated to be approximately 24 months. | Efficacy estimated as the Objective Response Rate (ORR) , which is the sum of Partial Response (PR) and Complete Response (CR) as determined by RECIST 1.1 |
| Half-life (T1/2) | Duration of the study, estimated to be approximately 24 months. | T1/2 of HL-085 following single and repeated dosing |
| Time to maximum observed plasma drug concentration (Tmax) | Duration of the study, estimated to be approximately 24 months. | Tmax of HL-085 following single and repeated dosing |
| Area under the plasma concentration versus time curve (AUC) | Duration of the study, estimated to be approximately 24 months | AUC of HL-085 following single and repeated dosing |
Countries
China
Outcome results
None listed