Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer
Primary Purpose
Advanced Breast Cancer
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
CYH33
Fulvestrant
Letrozole
Palbociclib
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Breast Cancer focused on measuring PIK3CA Mutant, Advanced Breast Cancer
Eligibility Criteria
Main Inclusion Criteria:
- Provide informed consent voluntarily.
- Male and female patients ≥ 18 years of age.
- Patient must have a histologically or cytologically documented locally advanced, recurrent or metastatic breast cancer.
- In case of women, both premenopausal and postmenopausal patients can be enrolled in the study.
- Confirmed diagnosis of HR+, HER2- breast cancer.
- For Stage 1 dose exploration phase, patients with or without PIK3CA mutation may be enrolled; For Stage 2 dose expansion phase, patients with PIK3CA mutations are required.
- Patient must have evidence of disease radiological progression after previous endocrine therapy, or other systemic therapy.
- Patient has measurable disease per RECIST v1.1.
- ECOG ≤ 1.
- Patient must have adequate organ and bone marrow function.
Main Exclusion Criteria:
- Previously received any anticancer therapy within 28 days or 5 times of half-lives prior to the first dose of the study treatment.
- Previously received treatment with any PI3Kα inhibitor, AKT inhibitor, or mTOR inhibitor.
- Radical radiation therapy within 4 weeks prior to the first dose of the study treatment.
- Patient with an established diagnosis of diabetes mellitus.
- Any other concurrent disease with potential risk of insulin resistance or current use of medication with potential risk of insulin resistance.
- Patient with clinically significant cardiovascular disease.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
CYH33 + fulvestrant
CYH33 + fulvestrant + palbociclib
CYH33 + letrozole + palbociclib
Arm Description
Participants will receive CYH33 in combination with a standard fixed dose of fulvestrant 500 mg.
Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg).
Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg)
Outcomes
Primary Outcome Measures
Dose Limiting Toxicities (DLT)
Incidence rate of DLT in the first cycle (of 28 days).
Secondary Outcome Measures
Safety and tolerability
Type, incidence, duration, severity and seriousness of adverse events (AEs).
Preliminary efficacy-ORR
Tumor objective response rate (ORR) assessed by RECIST v1.1
Preliminary efficacy-CBR
Clinical benefit rate (CBR) assessed by RECIST v1.1
Preliminary efficacy-PFS
Progression Free Survival (PFS) assessed by RECIST v1.1
Pharmacokinetic measures - AUC
Measure the variation of concentration in blood plasma as a function of time
Pharmacokinetic measures - C trough
Measure the minimum (trough) plasma concentration
Pharmacokinetic measures - Cmax
Measure the maximum (peak) plasma concentration
Pharmacokinetic measures - Tmax
Measure of time to reach maximum (peak) plasma concentration
Pharmacokinetic measures - CL/F
Measure apparent total clearance(s) from plasma after administration
Pharmacokinetic measures - Vz/F
Measure apparent volume of distribution during terminal phase
Assess downstream effects of PI3K pathway inhibition on blood glucose
Pre- and post-treatment of blood glucose
Assess downstream effects of PI3K pathway inhibition on C peptide
Pre- and post-treatment of C peptide
Assess the changes of biomarker-PIK3CA
Pre- and post-treatment PIK3CA changes in ctDNA samples.
Assess the changes of biomarker-PTEN
Pre- and post-treatment PTEN changes in ctDNA samples.
Assess the changes of biomarker-KRAS
Pre- and post-treatment KRAS changes in ctDNA samples.
Full Information
NCT ID
NCT04856371
First Posted
April 11, 2021
Last Updated
April 19, 2021
Sponsor
Haihe Biopharma Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04856371
Brief Title
Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer
Official Title
A Multicenter, Open-label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
April 2021 (Anticipated)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Haihe Biopharma Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a multicenter, open-label, phase Ib study designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CYH33 administered orally in combination with standard-of-care ET ± CDK4/6 inhibitor therapies for the treatment of locally advanced, recurrent or metastatic hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Patients will be enrolled in two stages, including dose exploration phase (Stage 1) and dose expansion phase (Stage 2) of each cohort.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Breast Cancer
Keywords
PIK3CA Mutant, Advanced Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
228 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CYH33 + fulvestrant
Arm Type
Experimental
Arm Description
Participants will receive CYH33 in combination with a standard fixed dose of fulvestrant 500 mg.
Arm Title
CYH33 + fulvestrant + palbociclib
Arm Type
Experimental
Arm Description
Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg).
Arm Title
CYH33 + letrozole + palbociclib
Arm Type
Experimental
Arm Description
Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg)
Intervention Type
Drug
Intervention Name(s)
CYH33
Intervention Description
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Intervention Description
Participants will receive fulvestrant 500 mg, administered intramuscularly on Days 1, 15 on Cycle 1 (28-day cycle) and Day 1 at each 28-day cycle thereafter.
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
Participants will receive oral letrozole once daily continuous on Day 1-28 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Intervention Description
Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicities (DLT)
Description
Incidence rate of DLT in the first cycle (of 28 days).
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Safety and tolerability
Description
Type, incidence, duration, severity and seriousness of adverse events (AEs).
Time Frame
30 months
Title
Preliminary efficacy-ORR
Description
Tumor objective response rate (ORR) assessed by RECIST v1.1
Time Frame
30 months
Title
Preliminary efficacy-CBR
Description
Clinical benefit rate (CBR) assessed by RECIST v1.1
Time Frame
30 months
Title
Preliminary efficacy-PFS
Description
Progression Free Survival (PFS) assessed by RECIST v1.1
Time Frame
30 months
Title
Pharmacokinetic measures - AUC
Description
Measure the variation of concentration in blood plasma as a function of time
Time Frame
20 months
Title
Pharmacokinetic measures - C trough
Description
Measure the minimum (trough) plasma concentration
Time Frame
20 months
Title
Pharmacokinetic measures - Cmax
Description
Measure the maximum (peak) plasma concentration
Time Frame
20 months
Title
Pharmacokinetic measures - Tmax
Description
Measure of time to reach maximum (peak) plasma concentration
Time Frame
20 months
Title
Pharmacokinetic measures - CL/F
Description
Measure apparent total clearance(s) from plasma after administration
Time Frame
20 months
Title
Pharmacokinetic measures - Vz/F
Description
Measure apparent volume of distribution during terminal phase
Time Frame
20 months
Title
Assess downstream effects of PI3K pathway inhibition on blood glucose
Description
Pre- and post-treatment of blood glucose
Time Frame
20 months
Title
Assess downstream effects of PI3K pathway inhibition on C peptide
Description
Pre- and post-treatment of C peptide
Time Frame
20 months
Title
Assess the changes of biomarker-PIK3CA
Description
Pre- and post-treatment PIK3CA changes in ctDNA samples.
Time Frame
20 months
Title
Assess the changes of biomarker-PTEN
Description
Pre- and post-treatment PTEN changes in ctDNA samples.
Time Frame
20 months
Title
Assess the changes of biomarker-KRAS
Description
Pre- and post-treatment KRAS changes in ctDNA samples.
Time Frame
20 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria:
Provide informed consent voluntarily.
Male and female patients ≥ 18 years of age.
Patient must have a histologically or cytologically documented locally advanced, recurrent or metastatic breast cancer.
In case of women, both premenopausal and postmenopausal patients can be enrolled in the study.
Confirmed diagnosis of HR+, HER2- breast cancer.
For Stage 1 dose exploration phase, patients with or without PIK3CA mutation may be enrolled; For Stage 2 dose expansion phase, patients with PIK3CA mutations are required.
Patient must have evidence of disease radiological progression after previous endocrine therapy, or other systemic therapy.
Patient has measurable disease per RECIST v1.1.
ECOG ≤ 1.
Patient must have adequate organ and bone marrow function.
Main Exclusion Criteria:
Previously received any anticancer therapy within 28 days or 5 times of half-lives prior to the first dose of the study treatment.
Previously received treatment with any PI3Kα inhibitor, AKT inhibitor, or mTOR inhibitor.
Radical radiation therapy within 4 weeks prior to the first dose of the study treatment.
Patient with an established diagnosis of diabetes mellitus.
Any other concurrent disease with potential risk of insulin resistance or current use of medication with potential risk of insulin resistance.
Patient with clinically significant cardiovascular disease.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yong Yuan, MD
Phone
86 13820384005
Email
yong.yuan@haihepharma.com
12. IPD Sharing Statement
Learn more about this trial
Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer
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