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出境医 / 临床实验 / Study of HL-085 in NRAS Mutant Advanced Melanoma

Study of HL-085 in NRAS Mutant Advanced Melanoma

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 .

Condition or disease Intervention/treatment Phase
Melanoma Drug: HL-085 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : March 1, 2022
Estimated Study Completion Date : March 1, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: HL-085
HL-085 will be administered as BID with specified dose.
 Drug: HL-085
HL-085 is one MEK inhibitor.
Outcome Measures
Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: 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

  2. Maximum tolerated dose (MTD) [ Time Frame: 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 Outcome Measures :
  1. Objective Response Rate (ORR) as measure of efficacy [ Time Frame: 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

  2. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    AUC of HL-085 following single and repeated dosing

  3. Peak Plasma Concentration (Cmax) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    Cmax of HL-085 following single and repeated dosing

  4. Time to maximum observed plasma drug concentration (Tmax) [ Time Frame: Duration of the study, estimated to be approximately 24 months. ]
    Tmax of HL-085 following single and repeated dosing

  5. Half-life (T1/2) [ Time Frame: Duration of the study, estimated to be approximately 24 months. ]
    T1/2 of HL-085 following single and repeated dosing


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Contacts
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Contact: Jin Ma, Bachelor 86 21 3810268600 maj@kechowpharma.com

Locations
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China, Beijing
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Jun Guo, M.D.    +86-10-88121122    guoj307@126.com   
Principal Investigator: Jun Guo, M.D.         
China, Shanghai
Fudan University Shanghai Cancer Center Recruiting
Shanghai, Shanghai, China
Sponsors and Collaborators
Shanghai Kechow Pharma, Inc.
Investigators
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Study Director: Hongqi Tian, Ph.D Shanghai Kechow Pharma, Inc.
Tracking Information
First Submitted Date  ICMJE December 19, 2017
First Posted Date  ICMJE June 4, 2019
Last Update Posted Date December 17, 2020
Actual Study Start Date  ICMJE September 1, 2017
Estimated Primary Completion Date March 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2019)
  • Number of participants with adverse events [ Time Frame: 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) [ Time Frame: 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)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2019)
  • Objective Response Rate (ORR) as measure of efficacy [ Time Frame: 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
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    AUC of HL-085 following single and repeated dosing
  • Peak Plasma Concentration (Cmax) [ Time Frame: Duration of the study, estimated to be approximately 24 months ]
    Cmax of HL-085 following single and repeated dosing
  • Time to maximum observed plasma drug concentration (Tmax) [ Time Frame: Duration of the study, estimated to be approximately 24 months. ]
    Tmax of HL-085 following single and repeated dosing
  • Half-life (T1/2) [ Time Frame: Duration of the study, estimated to be approximately 24 months. ]
    T1/2 of HL-085 following single and repeated dosing
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of HL-085 in NRAS Mutant Advanced Melanoma
Official Title  ICMJE 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
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 .
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE Drug: HL-085
HL-085 is one MEK inhibitor.
Study Arms  ICMJE Experimental: HL-085
HL-085 will be administered as BID with specified dose.
Intervention: Drug: HL-085
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 1, 2019) 		54
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 1, 2022
Estimated Primary Completion Date March 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jin Ma, Bachelor 86 21 3810268600 maj@kechowpharma.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03973151
Other Study ID Numbers  ICMJE HL-085-101
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Shanghai Kechow Pharma, Inc.
Study Sponsor  ICMJE Shanghai Kechow Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Hongqi Tian, Ph.D Shanghai Kechow Pharma, Inc.
PRS Account Shanghai Kechow Pharma, Inc.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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