Study of CYH33 in Combination With Endocrine Therapy With or Without Palbociclib in Patients With HR+, HER2- Advanced Breast Cancer

April 19, 2021 updated by: Haihe Biopharma Co., Ltd.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
228

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Main Inclusion Criteria:

  1. Provide informed consent voluntarily.
  2. Male and female patients ≥ 18 years of age.
  3. Patient must have a histologically or cytologically documented locally advanced, recurrent or metastatic breast cancer.
  4. In case of women, both premenopausal and postmenopausal patients can be enrolled in the study.
  5. Confirmed diagnosis of HR+, HER2- breast cancer.
  6. 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.
  7. Patient must have evidence of disease radiological progression after previous endocrine therapy, or other systemic therapy.
  8. Patient has measurable disease per RECIST v1.1.
  9. ECOG ≤ 1.
  10. Patient must have adequate organ and bone marrow function.

Main Exclusion Criteria:

  1. Previously received any anticancer therapy within 28 days or 5 times of half-lives prior to the first dose of the study treatment.
  2. Previously received treatment with any PI3Kα inhibitor, AKT inhibitor, or mTOR inhibitor.
  3. Radical radiation therapy within 4 weeks prior to the first dose of the study treatment.
  4. Patient with an established diagnosis of diabetes mellitus.
  5. Any other concurrent disease with potential risk of insulin resistance or current use of medication with potential risk of insulin resistance.
  6. Patient with clinically significant cardiovascular disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CYH33 + fulvestrant
Participants will receive CYH33 in combination with a standard fixed dose of fulvestrant 500 mg.
Drug: CYH33
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
Drug: Fulvestrant
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.
Experimental: CYH33 + fulvestrant + palbociclib
Participants will receive CYH33 in combination with standard fixed dose of fulvestrant (500 mg) and palbociclib (125 mg).
Drug: CYH33
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
Drug: Fulvestrant
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.
Drug: Palbociclib
Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.
Experimental: CYH33 + letrozole + palbociclib
Participants will receive CYH33 in combination with standard fixed dose of letrozole (2.5 mg) and palbociclib (125 mg)
Drug: CYH33
Participants will receive oral CYH33 once daily on Days 1-28 of each 28-day cycle.
Drug: Palbociclib
Participants will receive palbociclib once daily continuous on Day 1-21 of each 28-day cycle.
Drug: Letrozole
Participants will receive oral letrozole once daily continuous on Day 1-28 of each cycle.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicities (DLT)
Time Frame: 28 days
Incidence rate of DLT in the first cycle (of 28 days).
28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety and tolerability
Time Frame: 30 months
Type, incidence, duration, severity and seriousness of adverse events (AEs).
30 months
Preliminary efficacy-ORR
Time Frame: 30 months
Tumor objective response rate (ORR) assessed by RECIST v1.1
30 months
Preliminary efficacy-CBR
Time Frame: 30 months
Clinical benefit rate (CBR) assessed by RECIST v1.1
30 months
Preliminary efficacy-PFS
Time Frame: 30 months
Progression Free Survival (PFS) assessed by RECIST v1.1
30 months
Pharmacokinetic measures - AUC
Time Frame: 20 months
Measure the variation of concentration in blood plasma as a function of time
20 months
Pharmacokinetic measures - C trough
Time Frame: 20 months
Measure the minimum (trough) plasma concentration
20 months
Pharmacokinetic measures - Cmax
Time Frame: 20 months
Measure the maximum (peak) plasma concentration
20 months
Pharmacokinetic measures - Tmax
Time Frame: 20 months
Measure of time to reach maximum (peak) plasma concentration
20 months
Pharmacokinetic measures - CL/F
Time Frame: 20 months
Measure apparent total clearance(s) from plasma after administration
20 months
Pharmacokinetic measures - Vz/F
Time Frame: 20 months
Measure apparent volume of distribution during terminal phase
20 months
Assess downstream effects of PI3K pathway inhibition on blood glucose
Time Frame: 20 months
Pre- and post-treatment of blood glucose
20 months
Assess downstream effects of PI3K pathway inhibition on C peptide
Time Frame: 20 months
Pre- and post-treatment of C peptide
20 months
Assess the changes of biomarker-PIK3CA
Time Frame: 20 months
Pre- and post-treatment PIK3CA changes in ctDNA samples.
20 months
Assess the changes of biomarker-PTEN
Time Frame: 20 months
Pre- and post-treatment PTEN changes in ctDNA samples.
20 months
Assess the changes of biomarker-KRAS
Time Frame: 20 months
Pre- and post-treatment KRAS changes in ctDNA samples.
20 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Haihe Biopharma Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 11, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 23, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 23, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CYH33-G103

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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