Clinical Trials /

Phase I Study of HL-085 in Patients With Advanced Solid Tumors

NCT03976050

Description:

The study drug, HL-085 is a MEK inhibitor with the potential indication for cancers. It is an oral medication to be given daily. The purposes of this study is to find answers to the following research questions: 1. What is the highest tolerable dose of HL-085 that can be given to subjects when given orally (by mouth) on a twice daily basis? 2. What are the side effects of HL-085? 3. How much HL-085 is in the blood at specific times after dosing and how does the body get rid of the HL-085?

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of HL-085 in Patients With Advanced Solid Tumors
  • Official Title: A Phase I, Single Arm, Dose Escalation Study to Evaluate Safety, Pharmacokinetics and Preliminary Efficacy of HL-085 in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: HL-085-US-101
  • NCT ID: NCT03976050

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
HL-085No other interventionsDose escalation

Purpose

The study drug, HL-085 is a MEK inhibitor with the potential indication for cancers. It is an oral medication to be given daily. The purposes of this study is to find answers to the following research questions: 1. What is the highest tolerable dose of HL-085 that can be given to subjects when given orally (by mouth) on a twice daily basis? 2. What are the side effects of HL-085? 3. How much HL-085 is in the blood at specific times after dosing and how does the body get rid of the HL-085?

Trial Arms

NameTypeDescriptionInterventions
Dose escalationExperimentalSubjects in the dose escalation cohorts will receive ascending doses of HL-085 until the MTD is determined. The first three subjects will receive twice-daily doses (BID) of HL-085 6 mg. Additional cohorts may receive doses of HL-085 9, 12 or 18 mg BID respectively and sequentially. If DLTs are observed in <33.3% of subjects at the 18 mg dose.
  • HL-085

Eligibility Criteria

        Inclusion Criteria:

          1. Must have a pathologically documented solid tumor(s) that has relapsed from, or is
             refractory to standard treatment, or for which no standard treatment is available.

          2. Must have at least one measurable lesion as defined by RECISTv1.1 criteria for solid
             tumors.

          3. Must have received biological chemotherapy, immunotherapy or radiotherapy ≥4 weeks
             prior to starting the study treatment. Must have received small molecule chemotherapy
             ≥2 weeks or five half-lives (whichever is longer) prior to starting the study
             treatment.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          5. Life expectancy ≥3 months (as judged by the Investigator).

          6. Must have adequate hematologic, hepatic and renal function.

        Exclusion Criteria:

          1. Have undergone or plan to have major surgery or experienced severe trauma ≤28 days
             prior to starting the study treatment.

          2. Known hypersensitivity to IP ingredients or their analogues.

          3. Prior therapy with a MEK-inhibitor

          4. Receipt of any other investigational agent therapy within 4 weeks prior to starting
             study treatment.

          5. Any concurrent therapy for cancer treatment.

          6. Have active central nervous system lesion.

          7. Receiving and unable to discontinue medication which are strong inducers, strong
             inhibitors or enzyme substrates of cytochrome P450 CYP2C9 and CYP2C19 from 14 days
             prior to treatment.

          8. Grade 3 bleeding symptoms (NCI-CTCAE v5.0) within 4 weeks prior to starting study
             treatment.

          9. Unable to swallow IP or has refractory nausea and vomiting, malabsorption, external
             biliary diversion, or any significant small bowel resection that may interfere with
             adequate absorption of IP.

         10. ECG QTcB≥480msec in screening, or history of congenital long QT syndrome.

         11. Left ventricular ejection fraction (LVEF) <50%.

         12. History major cerebrovascular diseases within 6 months prior to enrollment.

         13. Infectious diseases requiring systemic treatment.

         14. History or current evidence of retinal diseases.

         15. Have active/chronic infection with hepatitis C, or positive hepatitis B surface
             antigen (HBsAg), or active/chronic infection with human immunodeficiency virus (HIV).

         16. Known active tuberculosis.

         17. History of allogeneic bone marrow transplantation or organ transplantation.

         18. Interstitial lung disease or interstitial pneumonitis, including clinically
             significant radiation pneumonitis.

         19. Pregnant or breast-feeding females.

         20. Previous or history of second malignancy within 5 years prior to study treatment

         21. Other conditions which may increase the risk associated with study participation, or
             interfere with the evaluation of study results.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events (AEs)
Time Frame:Duration of the study, estimated to be approximately 24 months.
Safety Issue:
Description:An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Secondary Outcome Measures

Measure:cMAX
Time Frame:Duration of the study, estimated to be approximately 24 months
Safety Issue:
Description:cMAX is the maximum plasma concentration of HL-085 or metabolite(s).
Measure:Overall response rate (ORR)
Time Frame:Duration of the study, estimated to be approximately 24 months
Safety Issue:
Description:ORR is the proportion of patients with a best overall response of complete response (CR) or partial response (PR), as assessed per response evaluation criteria in solid tumors (RECIST) v1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Shanghai Kechow Pharma, Inc.

Last Updated

June 24, 2019