Clinical Trials/NCT03415659

NCT03415659

Unknown

Phase 1

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

Hubei Biological Medicine Industrial Technology Institute Co., Ltd.1 site in 1 country85 target enrollmentMarch 5, 2018

ConditionsAdvanced Solid Tumors HRD BRCA Mutation

InterventionsHWH340 tablet

DrugsHWH340 tablet

Overview

Phase: Phase 1
Intervention: HWH340 tablet
Conditions: Advanced Solid Tumors
Sponsor: Hubei Biological Medicine Industrial Technology Institute Co., Ltd.
Enrollment: 85
Locations: 1
Primary Endpoint: Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability on single dose
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

March 5, 2018

End Date

September 30, 2021

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hubei Biological Medicine Industrial Technology Institute Co., Ltd.

Responsible Party

Sponsor

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.

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 HWH
•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.

Arms & Interventions

HWH340 monotherapy

HWH340 tablet, oral administration

Intervention: HWH340 tablet

Outcomes

Primary Outcomes

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

Number of Participants with adverse events

Number of Participants With Laboratory Test Abnormalities on single dose

Time Frame: up to 7 days after dosing

The laboratory test included: hematology, chemistry, urinalysis, and other tests

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) on multiple dose

Time Frame: up to 30 days after dosing

Number of Participants with adverse events

Number of Participants With Laboratory Test Abnormalities on multiple dose

Time Frame: up to 30 days after dosing

The laboratory test included: hematology, chemistry, urinalysis, and other tests

Secondary Outcomes

Maximum Observed Plasma Concentrations of platinum (Cmax)(Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose)
Area under the plasma concentration versus time curve (AUC)(Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose)
Time for Maximum Observed Plasma Concentration (Tmax)(Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose)
Disease Control Rate (DCR)(through study completion, an average of 1 year)
Objective Response Rate by Investigator(through study completion, an average of 1 year)
Disease control rate(through study completion, an average of 1 year)
Duration of response(through study completion, an average of 1 year)
Progression Free Survival(through study completion, an average of 1 year)
Tumor Objective Response Rate（ORR）(on day 42 post dose)
Best overall response(through study completion, an average of 1 year)