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Study of HL-085 in NRAS Mutant Advanced Melanoma

Primary Purpose

Melanoma

Status

Completed

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

HL-085

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Melanoma, NRAS

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma according to AJCC (Version 7, 2010).
Subjects must have NRAS mutation in melanoma.
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.
ECOG performance status of 0-1.
Life expectancy ≥ 3 months.
Ability to take the medicine orally.
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Prior therapy with a MEK-inhibitor
Patients with known hypersensitivity to study drug ingredients or their analogues.
Active central nervous system (CNS) lesion.
ECG QTcB≥480msec in screening, or history of congenital long QT syndrome.
Subjects with bleeding symptoms at Grade 3 (NCI-CTCAE v4.03) within 4 weeks prior to starting study treatment.
Uncontrolled concomitant diseases or infectious diseases.
Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.).
History of HIV,HCV,HBV infection.
Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded.
Serum HCG test is positive.
Other conditions that influence the results and increase the risk of study.

Sites / Locations

Beijing Cancer Hospital
Fudan University Shanghai Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HL-085

Arm Description

HL-085 will be administered as BID with specified dose.

Outcomes

Primary Outcome Measures

Number of participants with adverse events

Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 during the study period

Maximum tolerated dose (MTD)

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 Outcome Measures

Objective Response Rate (ORR) as measure of efficacy

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

Area under the plasma concentration versus time curve (AUC)

AUC of HL-085 following single and repeated dosing

Peak Plasma Concentration (Cmax)

Cmax of HL-085 following single and repeated dosing

Time to maximum observed plasma drug concentration (Tmax)

Tmax of HL-085 following single and repeated dosing

Half-life (T1/2)

T1/2 of HL-085 following single and repeated dosing

Full Information

NCT ID

NCT03973151

First Posted

December 19, 2017

Last Updated

May 29, 2023

Sponsor

Shanghai Kechow Pharma, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03973151

Brief Title

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

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

September 1, 2017 (Actual)

Primary Completion Date

January 18, 2021 (Actual)

Study Completion Date

January 18, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Kechow Pharma, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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 .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

Melanoma, NRAS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HL-085

Arm Type

Experimental

Arm Description

HL-085 will be administered as BID with specified dose.

Intervention Type

Drug

Intervention Name(s)

HL-085

Intervention Description

HL-085 is one MEK inhibitor.

Primary Outcome Measure Information:

Title

Number of participants with adverse events

Description

Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 during the study period

Time Frame

Duration of the study, estimated to be approximately 24 months.

Title

Maximum tolerated dose (MTD)

Description

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)

Time Frame

DLTs within the first cycle of therapy (up to 35 days)

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR) as measure of efficacy

Description

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

Time Frame

Duration of the study, estimated to be approximately 24 months.

Title

Area under the plasma concentration versus time curve (AUC)

Description

AUC of HL-085 following single and repeated dosing

Time Frame

Duration of the study, estimated to be approximately 24 months

Title

Peak Plasma Concentration (Cmax)

Description

Cmax of HL-085 following single and repeated dosing

Time Frame

Duration of the study, estimated to be approximately 24 months

Title

Time to maximum observed plasma drug concentration (Tmax)

Description

Tmax of HL-085 following single and repeated dosing

Time Frame

Duration of the study, estimated to be approximately 24 months.

Title

Half-life (T1/2)

Description

T1/2 of HL-085 following single and repeated dosing

Time Frame

Duration of the study, estimated to be approximately 24 months.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically or cytologically confirmed unresectable Stage III or Stage IV melanoma according to AJCC (Version 7, 2010). Subjects must have NRAS mutation in melanoma. 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. ECOG performance status of 0-1. Life expectancy ≥ 3 months. Ability to take the medicine orally. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Prior therapy with a MEK-inhibitor Patients with known hypersensitivity to study drug ingredients or their analogues. Active central nervous system (CNS) lesion. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome. Subjects with bleeding symptoms at Grade 3 (NCI-CTCAE v4.03) within 4 weeks prior to starting study treatment. Uncontrolled concomitant diseases or infectious diseases. Retinal diseases (Retinal Vein Occlusion (RVO) or Retinal pigment epithelial detachment (RPED) , et al.). History of HIV,HCV,HBV infection. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis will be excluded. Serum HCG test is positive. Other conditions that influence the results and increase the risk of study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hongqi Tian, Ph.D

Organizational Affiliation

Shanghai Kechow Pharma, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Beijing Cancer Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100142

Country

China

Facility Name

Fudan University Shanghai Cancer Center

City

Shanghai

State/Province

Shanghai

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Study of HL-085 in NRAS Mutant Advanced Melanoma

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