Clinical Trials /

Phase I Clinical Study of HWH340 Tablet in Patients With Advanced Solid Tumors

NCT03415659

Description:

This is an open-label, dose-escalation/dose-expansion, phase I clinical trial study to investigate the safety, tolerability, and efficacy of HWH340. In addition, the pharmacokinetic characteristics will also be investigated. Three parts are included in this study.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Clinical Study of HWH340 Tablet in Patients With Advanced Solid Tumors
  • Official Title: A Phase I, Open-label, Single-center, Single/Multiple-dose, Dose-escalation/Dose-expansion Clinical Study on Tolerance and Pharmacokinetics of HWH340 Tablet in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: HWH340-RFPA 20170821
  • NCT ID: NCT03415659

Conditions

  • Advanced Solid Tumors
  • HRD
  • BRCA Mutation

Interventions

DrugSynonymsArms
HWH340 tabletHWH340 monotherapy

Purpose

This is an open-label, dose-escalation/dose-expansion, phase I clinical trial study to investigate the safety, tolerability, and efficacy of HWH340. In addition, the pharmacokinetic characteristics will also be investigated. Three parts are included in this study.

Detailed Description

      Part one is a single-dose study on tolerance and pharmacokinetics, in which 21-42 patients
      with advanced solid tumors would be enrolled. Patients will receive escalating dose groups of
      HWH340 tablet.

      Part two is a multiple-dose study on tolerance and pharmacokinetics. Based on the safety
      assessment, three or four groups would be chosen to conduct the study. 9-24 patients with
      advanced solid tumors will be enrolled.

      Part three is a dose expansion stage on safety and efficacy. Two to four dose-groups would be
      chosen to conduct the study. 40-60 patients with advanced solid tumors with BRCA mutation OR
      homologous recombination deficiency (HRD) will be enrolled.
    

Trial Arms

NameTypeDescriptionInterventions
HWH340 monotherapyExperimentalHWH340 tablet, oral administration
  • HWH340 tablet

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with the advanced solid tumors, which have been histologically and/ or
             cytologically confirmed.

          -  Patients with advanced solid tumors refractory to standard therapy or for whom no
             suitable effective standard therapy exists.

          -  patients in dose expansion stage must meet the following conditions:

          -  Group 1: Germline and/or systemic BRCA1/2 mutation;

          -  Group 2: HRD related gene (except BRCA 1/2) mutation;

          -  For breast cancer patients, Histologically or cytologically confirmed HER2(-), and
             received ≤3 prior lines of chemotherapy in advanced or metastatic setting;

          -  18 ≤ years of age ≤ 70

          -  Expected survival time ≥ 6 months

          -  No serious hematopoietic dysfunction exists. Also, normal function of bone marrow and
             organs such as heart, lung, liver and kidney are required. Within 14 days prior to
             inclusion, the patients' laboratory examination results must be within normal
             limits(under the condition of no extra growth factor or blood transfusion): Blood
             routine examination: Absolute neutrophil count( ANC) ≥ 1.5 × 109/L),Platelets(PLT) ≥
             100 × 109/L, Hemoglobin(Hb) ≥ 100 g/L;Renal function: Serum creatinine (Cr) ≤1.5×ULN
             ;Hepatic function: Total Bilirubin ≤1.5×ULN, AST and ALT ≤ 2.5 ×ULN (For patients with
             liver metastases, AST and ALT ≤ 5 × ULN) ;Electrolytes: normal value ranges (sodium,
             potassium and calcium);Coagulation function: International Normalized Ratio( INR)
             ≤1.5, Activated partial thromboplastin time(APTT) ≤ 1.5 × ULN;

          -  Patients of reproductive potential must agree to practice effective medically approved
             contraceptive methods during the trial and 6 months afterwards. Women of childbearing
             potential must have a negative pregnancy test within 7 days prior to screening.

          -  Subject must fully understand this study, sign informed consent on a voluntary basis ,
             comply with procedures and follow-up examinations as outlined in the protocol and
             agree to have the gene test.

          -  Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 (patients in the
             multiple-dose study)

          -  Multiple-dose patients must have no less than one measurable tumor according to RECIST
             1.1 criteria.

        Exclusion Criteria:

          -  Subject who has other serious and/or uncontrollable damaged vital organs or unstable
             systemic disease besides tumors. These diseases include but not limit to uncontrolled
             diabetes, unstable angina pectoris , cerebrovascular accident or transient cerebral
             ischemia( within 6 months prior to screening), myocardial infarction (within 6 months
             prior to screening), congestive heart-failure , uncontrolled high blood pressure,
             active or uncontrollable infection, hepatic/renal/metabolic disease, serious
             gastrointestinal disease, any mental disease that may affect study abidance ; or any
             medical conditions, which in the opinion of the study investigators, places the
             subject at an unacceptably high risk of toxicities and interfere with the study.

          -  Subject who has previously been treated with PARP inhibitors, including any related
             clinical trials, except for HWH340. Subjects in dose expansion stage who have
             previously received PARP inhibitors (including drug clinical trials), except for
             patients who have not reached a therapeutic dose with a PARP inhibitor, or patients
             who have used a PARP inhibitor which is not first-line treatment for ≤ 28 days;

          -  Subject who has received the treatments of inhibitors of CYP3A3 and/or CYP2D6 within 2
             weeks.

          -  Subject who has received chemotherapy, radiotherapy, endocrinotherapy, biotherapy,
             immunotherapy, Chinese herbal treatment or other anti-tumor treatment within 4 weeks
             prior to initiation of this study.In the dose expansion stage, except for patients who
             have begun bisphosphonate or RANK-L inhibitors with stable dose for bone metastases
             before enrollment.

          -  Subject who has participated in other clinical trials or used other investigational
             drug within 3 weeks prior to initiation of this study.

          -  Subject who has the autoimmune disease, immunodeficiency disease or surgical history
             of organ transplantation.

          -  Positive results of HBsAg, HCV antibody, HIV antibody or Syphilis. Patient who has
             chronic toxic reaction (≥ CTCAE Grade 2) caused by prophase treatment, except the
             hair-loss patients.

          -  Subject who has experienced major surgery and has not been fully rehabilitated within
             4 weeks prior to this study.

          -  Subject who is allergic to the investigational drug or similar drugs, or has the
             history of allergic disease, or is in allergic constitution.

          -  History of alcohol addiction or abuse.

          -  Pregnant /lactating women.

          -  Subject who has the symptoms of CNS metastases.

          -  History of gastrointestinal dysfunction and difficulty in swallowing that may
             influence the drug absorption.

          -  Subject who has received blood transfusion within 4 weeks prior to the study.

          -  Subject who attends the study is not on a voluntary basis or cannot comply with the
             protocol.

          -  Judged by the investigator, for any reason, that the subject is an unsuitable
             candidate.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability on single dose
Time Frame:up to 7 days after dosing
Safety Issue:
Description:Number of Participants with adverse events

Secondary Outcome Measures

Measure:Maximum Observed Plasma Concentrations of platinum (Cmax)
Time Frame:Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Safety Issue:
Description:Blood samples are obtained and plasma concentrations of HWH340 are determined using a validated atomic absorption spectrometry method.
Measure:Tumor Objective Response Rate(ORR)
Time Frame:on day 42 post dose
Safety Issue:
Description:Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Safety Issue:
Description:AUC referred to area under the plasma concentration-time curve post dose.
Measure:Time for Maximum Observed Plasma Concentration (Tmax)
Time Frame:Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Safety Issue:
Description:Blood samples are obtained and plasma concentrations of HWH340 are determined using a validated atomic absorption spectrometry method.
Measure:Disease Control Rate (DCR)
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measure:Objective Response Rate by Investigator
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measure:Disease control rate
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measure:Duration of response
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measure:Best overall response
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measure:Progression Free Survival
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hubei Biological Medicine Industrial Technology Institute Co., Ltd.

Trial Keywords

  • HWH340
  • pharmacokinetics
  • dose-escalation
  • safety
  • efficacy
  • dose-expansion

Last Updated

February 12, 2020