PhaseⅠStudy of the HS-10241 in Patients With Advanced Solid Tumors

NCT04477057 | Unknown Phase 1

• 1 other identifier: HS-10241-101-CN
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

HS-10241 is a highly potent and selective small molecule inhibitor of c-Met kinase. In preclinical studies, it demonstrated strong activity against c-Met kinase in vitro and in vivo, and inhibited tumor cell growth. This study is conducted to assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of HS-10241 at single dose and multiple doses.

Conditions

Solid Tumor

Keywords

phase 1, solid tumor, inhibitor of c-Met kinase

Outcome Measures

Primary Outcomes (2)

• Number of subjects with any dose limiting toxicity (DLT)

  DLT is defined as one of the following HS-10241 related adverse event (AE) that occurs during the DLT period, excluding AE assessed by investigator exclusively related to subject's underlying disease or medical condition (graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0): Grade 4 hematological toxicity and Grade ≥ 3 non-hematological toxicity.

  From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (4 weeks).

• To determine the maximum tolerated dose (MTD)

  MTD was defined as the previous dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT.

  From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (4 weeks).

Secondary Outcomes (15)

• Incidence and severity of treatment-emergent adverse events

  From baseline until 28 days after the last dose

• Observed maximum plasma concentration (Cmax) after single dose of HS-10241

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24,48, 72,120 hours post-dose on Day 1 single dose

• Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-10241

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of dosing in the second 21-Day cycle of therapy

• Time to reach maximum plasma concentration (Tmax) after single dose of HS-10241

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24,48, 72,120 hours post-dose on Day 1 single dose

• Time to reach maximum plasma concentration (Tmax) after multiple dose of HS-10241

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of dosing in the second 21-Day cycle of therapy

Study Arms (1)

one arm

OTHER

one arm

Drug: HS-10241

Interventions

HS-10241 DRUG

HS-10241 is a tablet in the form of 100 mg, oral, once daily.

one arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form.
• Men or women aged more than or equal to (≥) 18 years, and less than (\<) 75 years.
• Histologically or cytologically confirmed solid tumor, either refractory to standard therapy or for which no effective standard therapy is available.
• ECOG performance status of 0-1, estimated life expectancy greater than (\>) three months.
• At least 1 lesion that has not previously been irradiated, that has not been chosen for biopsy during the study screening period, and that can be accurately measured at Baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), whichever is suitable for accurately repeated measurements.
• Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling 1 of the following criteria at Screening:
• Postmenopausal defined as age more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
• Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more, following cessation of exogenous hormonal treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not by tubal ligation.
• Male patients should be willing to use barrier contraception (i.e., condoms).

You may not qualify if:

• Treatment with any of the following:
• Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for the treatment of advanced solid tumor used for a previous treatment regimen or clinical study within 14 days of the first dose of study drug.
• Drugs with immunoregulatory indications within 7 days of the first dose of study drug.
• Medications that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug.
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) , unrecovered wound, ulcer, or fracture within 4 weeks of the first dose of study drug.
• Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study drug, with the exception of patients receiving radiation to \> 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
• Previous or current treatment with drugs targeting the c-MET/HGF pathway.
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the exception of alopecia.
• Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 2 weeks prior to start of study treatment. Meningeal or brainstem metastases.
• Pleural or peritoneal effusion requiring clinical intervention (except for effusion stable at least 1 week after clinical intervention). Pericardial effusion (except for non-tumorous micro pericardial effusions).
• The tumor compresses or invades important surrounding organs (such as trachea, esophagus, superior vena cava, heart, and aorta, etc), or causes significant mediastinal displacement.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension or active bleeding diatheses, which, in the investigator's opinion, makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol such as active infection (e.g., hepatitis B, hepatitis C, or human immunodeficiency virus \[HIV\]). Screening for chronic conditions is not required.
• Any active infection requiring treatment or systemic anti-infective agent used in one week prior to first dose administration.
• Active hemoptysis, active diverticulitis, peritoneal abscess, gastrointestinal obstruction that requires clinical intervention.
• Medical history of arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, within 6 months prior to screening. Medical history of deep vein thrombosis, pulmonary embolism, or any other serious thromboembolism within 3 months prior to screening.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 100021, China

RECRUITING

Study Officials

• Shun Lu

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

• Shenglin Ma

  First People's Hospital of Hangzhou

  PRINCIPAL INVESTIGATOR

• Deguang Mu

  Zhejiang Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• Jianhua Chen

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Xiaorong Dong

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

• Xiaoju Zhang

  Henan Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• Xingya Li

  The First Affiliated Hospital of Zhengzhou University

  PRINCIPAL INVESTIGATOR

• 7Yubiao Guo

  First Affiliated Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tianyu Sun

CONTACT

13817295181; sunty@hspharm.com

Study Design

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

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: July 20, 2020
• Study Start: June 21, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2021
• Last Updated: July 20, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)