Clinical trial NCT03973151: Study of HL-085 in NRAS Mutant Advanced Melanoma
Official title: A Phase I/II, Single Arm, Dose Escalation and Cohort Expansion Study to Evaluate Safety, Preliminary Efficacy of HL-085 in Patients With NRAS Mutant Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Melanoma
Keywords: Melanoma
NRAS
Lead sponsor: Shanghai Kechow Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-04
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 .


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Duration of the study, estimated to be approximately 24 months.
measure: Maximum tolerated dose (MTD)
timeFrame: DLTs within the first cycle of therapy (up to 35 days)
Secondary outcomes:
measure: Objective Response Rate (ORR) as measure of efficacy
timeFrame: Duration of the study, estimated to be approximately 24 months.
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Duration of the study, estimated to be approximately 24 months
measure: Peak Plasma Concentration (Cmax)
timeFrame: Duration of the study, estimated to be approximately 24 months
measure: Time to maximum observed plasma drug concentration (Tmax)
timeFrame: Duration of the study, estimated to be approximately 24 months.
measure: Half-life (T1/2)
timeFrame: Duration of the study, estimated to be approximately 24 months.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Shanghai Kechow Pharma, Inc.
name: Hongqi Tian, Ph.D
role: STUDY_DIRECTOR
References: