Study of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC

NCT03990077 | Terminated Phase 1

• 1 other identifier: HL-085-103
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, open label, dose escalation study to evaluate tolerability, safety , pharmacokinetics and efficacy in patients with KRAS mutant NSCLC by using HL-085 and Docetaxel.

Conditions

Nsclc

Outcome Measures

Primary Outcomes (2)

• Number of Adverse Events (AEs)

  Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.03 will be counted.

  Duration of the study, estimated to be approximately 24 months

• Maximum tolerated dose (MTD)

  The dose level immediately below the dose level at which more than 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity (DLT)

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

Secondary Outcomes (3)

• Overall response rate (ORR)

  Duration of the study, estimated to be approximately 24 months

• Peak Plasma Concentration (Cmax)

  Duration of the study, estimated to be approximately 24 months

• Area under the plasma concentration verus time curve(AUC)

  Duration of the study, estimated to be approximately 24 months

Study Arms (1)

dose escalation of HL-085 plus Docetaxel

EXPERIMENTAL

HL-085 will be administered as BID with specified dose. And Docetaxel will be taken as the instruction in the label ( 75mg/m2，IV). f no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.

Drug: HL-085; Drug: Docetaxel

Interventions

HL-085 DRUG

HL-085 ( Capsule) is one MEK inhibitor.

dose escalation of HL-085 plus Docetaxel

Docetaxel DRUG

Docetaxel is an antineoplastic drug by inhibiting microtubule depolymerization, and attenuating of the effects of bcl-2 and bcl-xL gene expression.

dose escalation of HL-085 plus Docetaxel

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• KRAS mutation NSCLC.
• One measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
• 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.

You may not qualify if:

• Hypersensitivity to study drug ingredients or their analogues.
• Prior therapy with MEK-inhibitor.
• Receiving any other anti-cancer therapy at the same time .
• Active central nervous system (CNS) lesion.
• Bleeding symptoms at Grade 3 within 4 weeks prior to starting study treatment.
• ECG QTcB≥480msec in screening, or history of congenital long QT syndrome；
• 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 increase the risk of study and influence the result.

Sponsors & Collaborators

• Shanghai Kechow Pharma, Inc.: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Science

Beijing, 100021, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Hongqi Tian, PhD

  Shanghai Kechow Pharma.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: If no Dose-limiting toxicity (DLT) occurs in the first three subjects in Cycle 1, the dose will be escalated to the next dose level; If a DLT occurs in one of the first three subjects, three additional subjects will be enrolled for the same dose cohort, and undergo the same procedures. Dose -escalation is performed based on the scheduled dose groups until DLT occurs in two or more subjects in a dose group which consists of 3 or 6 subjects.

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: June 18, 2019
• Study Start: May 21, 2020
• Primary Completion: July 20, 2021
• Study Completion: July 20, 2021
• Last Updated: December 10, 2021

Record last verified: 2020-12

Locations

CN (1)