Phase I Study of the HS-10352 in Patients With Advanced Breast Cancer

NCT04631835 | Unknown Phase 1

• 1 other identifier: HS-10352-101
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 3

Brief Summary

HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide 3-kinase (p110α). In preclinical studies, it demonstrated strong activity against PI3K p110α in vitro and in vivo, and inhibited tumor cell growth. The first-in-human trial 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-10352 at single dose and multiple doses.

Conditions

Breast Cancer

Keywords

dose-escalation; advanced solid tumors; estrogen receptor positive breast cancer; PIK3CA gene mutation

Outcome Measures

Primary Outcomes (2)

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

  DLT is defined as one of the following HS-10352 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):

  From the single dose to the last dose of the first cycle defined as 28 days of multiple dosing (35 days).

• To determine the maximum tolerated dose (MTD)

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

  From the single dose to the last dose of the first cycle defined as 28 days of multiple dosing (35 days).

Secondary Outcomes (14)

• 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-10352

  From pre-dose to 120 hours after single dose on Day 1

• Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-10352

  From pre-dose to 24 hours after the first dose of multiple dosing on Day 1 of the second 28-Day cycle of therapy

• Time to reach maximum plasma concentration (Tmax) after single dose of HS-10352

  From pre-dose to 120 hours after single dose on Day 1

• Time to reach maximum plasma concentration (Tmax) after multiple dose of HS-10352

  From pre-dose to 24 hours after the first dose of multiple dosing on Day 1 of the second 28-Day cycle of therapy

Study Arms (1)

HS-10352

EXPERIMENTAL

There are five escalating dose cohorts

Drug: HS-10352

Interventions

HS-10352 DRUG

Participants will receive single dose of HS-10352 on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

HS-10352

Eligibility Criteria

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

You may qualify if:

• Men or women aged more than or equal to (≥) 18 years, and less than (\<) 75 years.
• HR+ HER2- locally advanced or metastatic breast cancer patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable.
• Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required)
• ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.
• Estimated life expectancy greater than (\>) three months.
• 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 evidence of non-childbearing potential.
• Sign Informed Consent Form.

You may not qualify if:

• Treatment with any of the following:
• Previous or current treatment with PI3K, AKT or mTOR inhibitors.
• Any cytotoxic chemotherapy, investigational agents within 21 days of the first dose of study drug; anticancer drugs which have been received within 14 days before the first administration.
• Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.
• Inadequate bone marrow reserve or organ function.
• Uncontrolled pleural effusion or ascites or pericardial effusion.
• Known and untreated, or active central nervous system metastases.
• History of primary or secondary diabetes.
• History of acute or chronic pancreatitis
• Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10352.
• History of hypersensitivity to any active or inactive ingredient of HS-10352 or to drugs with a similar chemical structure or class to HS-10352.
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
• Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (3)

SUN YAT-SEN Memorial Hospital

Guanzhou, Guangdong, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

RECRUITING

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Related Publications (1)

• Ouyang Q, Wang Y, Zhang J, Wu Q, Wei H, Li C, Qian X, Hu X. HS-10352 in hormone receptor-positive, HER2-negative advanced breast cancer: A phase 1 dose-escalation trial. Cancer Med. 2023 Dec;12(24):21849-21860. doi: 10.1002/cam4.6755. Epub 2023 Dec 1.

  PMID: 38037839 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Xichun Hu

CONTACT

086-021-64175590; xchu2009@hotmail.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: November 9, 2020
• First Posted: November 17, 2020
• Study Start: September 8, 2020
• Primary Completion: April 30, 2023
• Study Completion: August 31, 2023
• Last Updated: June 15, 2022

Record last verified: 2022-06

Locations

CN (3)