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

NCT03415659 | Unknown Phase 1

• 1 other identifier: HWH340-RFPA 20170821
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumors; HRD; BRCA Mutation

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability on single dose

  Number of Participants with adverse events

  up to 7 days after dosing

• Number of Participants With Laboratory Test Abnormalities on single dose

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

  up to 7 days after dosing

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

  Number of Participants with adverse events

  up to 30 days after dosing

• Number of Participants With Laboratory Test Abnormalities on multiple dose

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

  up to 30 days after dosing

Secondary Outcomes (10)

• 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

• Tumor Objective Response Rate（ORR）

  on day 42 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

Study Arms (1)

HWH340 monotherapy

EXPERIMENTAL

HWH340 tablet, oral administration

Drug: HWH340 tablet

Interventions

HWH340 tablet DRUG

1. single escalating dose study starts from 20 mg as the initial dose until the maximum dose group (520mg) or maximum tolerated dose (MTD) has been reached. 2. multiple-dose study conducted on oral HWH340 tablet BID. The DLTs evaluating period is 4 weeks and the safety evaluation period lasts till 4 weeks after drug withdrawal. 3. dose-expansion study conducted on oral HWH340 tablet BID in 2 to 4 dose groups. Patients with BRCA mutation OR HRD will be assigned to 2 cohort in each dose group.

HWH340 monotherapy

Eligibility Criteria

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

You may qualify if:

• 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;
• ≤ years of age ≤ 70
• Expected survival time ≥ 6 months
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hubei Biological Medicine Industrial Technology Institute Co., Ltd.: lead

Study Sites (1)

Tianjin medical university cancer insititute & hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Study Officials

• TONG Zhongsheng

  Professor of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

HE Zhenyu

CONTACT

+86-027-87171568; hezhenyu@renfu.com.cn

SUN Wenjie

CONTACT

+86-027-87171568; sunwenjie@renfu.com.cn

Study Design

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

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: January 30, 2018
• Study Start: March 5, 2018
• Primary Completion: March 30, 2021
• Study Completion: September 30, 2021
• Last Updated: February 17, 2020

Record last verified: 2020-02

Locations

CN (1)