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Trial Title:
A Phase Ib Study of HS-10352 Plus Fulvestrant in Patients With Advanced Breast Cancer
NCT ID:
NCT05504213
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Fulvestrant
Conditions: Keywords:
dose-escalation
dose-expansion
advanced breast cancer
hormone receptor positive
PIK3CA gene mutation
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
HS-10352 combined with fulvestrant (Stage 1)
Description:
Drug: HS-10352 HS-10352 will be administered at escalating doses orally once daily on a
continuous dosing schedule starting on Cycle 1 Day 1 (C1D1) in a 28 day cycle.
Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle
1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).
Arm group label:
Cohort 1: Endocrine therapy-resistant (Stage 1)
Intervention type:
Drug
Intervention name:
HS-10352 combined with fulvestrant (Stage 2)
Description:
Drug: HS-10352 participants will be enrolled into Cohort 2 (endocrine therapy-resistant)
and Cohort 3 (endocrine therapy-sensitive or naïve) respectively and HS-10352 will be
administered at the recommended dose identified in Part 1.
Drug: Fulvestrant Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle
1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).
Arm group label:
Cohort 2: Endocrine therapy-resistant (Stage 2)
Arm group label:
Cohort 3: Endocrine therapy-sensitive or endocrine-naïve (Stage 2)
Summary:
HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide
3-kinase (p110α). The purpose of this study is to assess the safety, tolerability,
pharmacokinetics (PK), and efficacy of HS-10352 plus fulvestrant in patients with hormone
receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast
cancer (ABC) harboring PIK3CA mutations.
Detailed description:
This is a Phase Ib open-label, 2-Part, multi-center study in China. The study will be
conducted in two stages: Stage 1 is the dose-escalation part, which is designed to
evaluate the safety, tolerability, PK and efficacy, as well as to determine the maximum
tolerable dosage (MTD) or maximum applicable dose (MAD) of HS-10352 in combination with
fulvestrant. Stage 2 is the dose-expansion part, which is aimed to further assess the
efficacy, safety, tolerability and PK, and to establish the recommended phase 2 dose
(RP2D) of HS-10352 in combination with fulvestrant.
All participants will be carefully monitored for adverse events (AE) during the study
treatment and for 28 days after the last dose of study drug. The PK characteristics of
HS-10352 and fulvestrant will be evaluated from C1 to C6. Subjects of this study will be
assessed for progression once every 8 weeks until objective disease progression or
withdrawal from the trial. As the disease progresses, survival follow-up is recommended
bimonthly.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Men or women aged more than or equal to (≥) 18 years
2. HR+ HER2- breast cancer confirmed by histology or cytology.
3. Locally advanced disease not amenable to curative treatment by surgery or metastatic
disease.
4. Have adequate tumor tissue for the analysis of PIK3CA mutational status. At dose
expansion stage, participants should be identified as PIK3CA-mutation positive
before enrollment.
5. Females should have postmenopausal status due to either surgical/natural menopause
or ovarian suppression with a luteinizing hormone releasing hormone (LHRH) agonist
before enrollment. Males should be pre-treated with a LHRH agonist.
6. Have either measurable disease per RECIST v1.1 criteria or at least one
predominantly lytic bone lesion must be present.
7. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.
8. Estimated life expectancy for at least three months
9. Females should be using adequate contraceptive measures and should not be
breastfeeding at the time of screening, during the study and until 6 months after
completion of the study; and have negative results of blood pregnancy test prior to
C1D1.
Males should be using adequate contraceptive measures at the time of screening,
during the study and until 6 months after completion of the study.
10. Have signed Informed Consent Form
11. Dose escalation stage-Cohort 1: subjects resistant to endocrine therapy Dose
expansion stage-Cohort 2: subjects resistant to endocrine therapy Dose expansion
stage-Cohort 3: endocrine therapy-sensitive or endocrine-naive subjects
Exclusion Criteria:
1. Participant with symptomatic visceral disease or any disease burden that makes the
participant ineligible for endocrine therapy per the investigator's best judgment
2. Treatment with any of the following:
1. Previous or current treatment with PI3K, AKT or mTOR inhibitors
2. For expansion stage, prior treatment with fulvestrant
3. 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.
4. 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.
5. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4
weeks of the first dose of study drug.
3. With inflammatory breast cancer at screening.
4. Inadequate bone marrow reserve or organ function.
5. Uncontrolled pleural effusion or ascites or pericardial effusion.
6. Known and untreated, or active central nervous system metastases.
7. History of primary or secondary diabetes.
8. History of acute or chronic pancreatitis
9. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to
swallow the study drug that would preclude adequate absorption of HS-10352 or
fulvestrant.
10. History of hypersensitivity to any active or inactive ingredient of HS-10352/
fulvestrant or to drugs with a similar chemical structure or class to HS-10352.
11. 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.
12. Any disease or condition that, in the opinion of the investigator, would compromise
the safety of the patient or interfere with study assessments.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Xichun Hu, PhD
Phone:
021-64175590
Email:
xchu2009@hotmail.com
Contact backup:
Last name:
Jian Zhang, PhD
Phone:
021-64175590
Phone ext:
86500
Email:
syner2000@163.com
Start date:
January 12, 2022
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05504213