Back to resultsDalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy
Primary Purpose
Breast Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Dalpiciclib
Pyrotinib
Fulvestrant
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria: Men or women at least 18 years of age with histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease. Most recent tumor biopsy or surgical resection specimen must be either estrogen-receptor (ER) positive, progesterone receptors (PgR) positive, or both, as defined by immunohistochemistry (IHC) ≥1% (as per the American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines). HER2-low breast cancer defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested). (as per the ASCO-CAP guidelines). Postmenopausal status or receiving ovarian ablation with a GnRH agonist such as goserelin. Postmenopausal status is defined by any one of the following criteria: Prior bilateral oophorectomy. Age ≥60 years. Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH, LH, and estradiol in the postmenopausal range per local normal If the patient does not meet criteria for postmenopausal status but is receiving ovarian ablation therapy with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin, the patient is eligible for this study, provided that the GnRH agonist is started at least 2 weeks prior to C1D1 of anti-estrogen therapy. Patient must have either measurable disease by RECIST 1.1 or only bone lesions in absence of measurable disease. Eastern Cooperative Group (ECOG) performance status of 0 or 1. Previously treated on CDK 4/6 inhibitor(palbociclib, abemaciclib or ribociclib) with AI for at least 6 months Adequate bone marrow and organ function. Exclusion Criteria: Patient with symptomatic visceral disease or any disease burden. Patient has received more than one line of chemotherapy for advanced disease. Previous treatment with Dalpiciclib /Pyrotinib /ADCe for advanced disease. Progressed on more than one CDK 4/6 inhibitor Patients with persistent symptoms and unstable brain metastases; Any condition that makes the patient ineligible for endocrine therapy per the investigator's best judgment
Sites / Locations
- Tianjin Cancer Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dalpiciclib, Fulvestrant With Pyrotinib
Arm Description
Pyrotinib 320mg/day Dalpiciclib 125 mg/day Fulvestrant 500mg
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS) as Assessed by the Investigator
Progression free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Secondary Outcome Measures
Overall Response Rate (ORR)
Evaluation of disease will be made according to RECIST criteria (version 1.1) in patients with measurable disease. As this study will enroll patients with measureable and un-measurable disease as defined by RECIST v1.1, ORR will only be assessed in evaluable patients. Response rates will be estimated as the proportion of enrolled patients who achieve complete or partial response rate.
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) is defined as the percentage of participants with a complete response (CR) or partial response (PR) or with stable disease (SD) as per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 or Non-Complete Response or Non-Progressive Disease (NCRNPD) during first 24 weeks of first dose. CR=disappearance of all non-nodal target lesions, PR=at least a 30% decrease in the sum of diameter of all target lesions, SD=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD), PD=at least a 20% increase in the sum of diameter of all target lesions.
Overall Survival (OS)
Overall survival is the time from date of first treatment to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the last date of contact.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)
An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Full Information
NCT ID
NCT05806671
First Posted
March 28, 2023
Last Updated
March 28, 2023
Sponsor
Tianjin Medical University Cancer Institute and Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05806671
Brief Title
Dalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy
Official Title
A Phase II, Single Arm, Open-label Trial of Dalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2023 (Anticipated)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tianjin Medical University Cancer Institute and Hospital
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
The purpose of this study is to determine if the triplet combination of dalpiciclib, fulvestrant, and pyrotinib is safe and effective in the treatment of hormone receptor-positive, HER2-low locally advanced/metastatic breast cancer following treatment with an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib abemaciclib or ribociclib).
The study will employ a Bayesian Optimal Phase II (BOP2) design which explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs, and has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dalpiciclib, Fulvestrant With Pyrotinib
Arm Type
Experimental
Arm Description
Pyrotinib 320mg/day Dalpiciclib 125 mg/day Fulvestrant 500mg
Intervention Type
Drug
Intervention Name(s)
Dalpiciclib
Other Intervention Name(s)
SHR6390
Intervention Description
Dalpiciclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off
Intervention Type
Drug
Intervention Name(s)
Pyrotinib
Intervention Description
Pyrotinib 320mg/day orally continuously
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Intervention Description
Fulvestrant 500mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) as Assessed by the Investigator
Description
Progression free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time Frame
From start date to date of first documentation of progression or death (assessed up to 12 months)
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Evaluation of disease will be made according to RECIST criteria (version 1.1) in patients with measurable disease. As this study will enroll patients with measureable and un-measurable disease as defined by RECIST v1.1, ORR will only be assessed in evaluable patients. Response rates will be estimated as the proportion of enrolled patients who achieve complete or partial response rate.
Time Frame
From start date to date of first documentation of progression or death (assessed up to 12 months)
Title
Clinical Benefit Rate (CBR)
Description
Clinical Benefit Rate (CBR) is defined as the percentage of participants with a complete response (CR) or partial response (PR) or with stable disease (SD) as per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 or Non-Complete Response or Non-Progressive Disease (NCRNPD) during first 24 weeks of first dose. CR=disappearance of all non-nodal target lesions, PR=at least a 30% decrease in the sum of diameter of all target lesions, SD=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD), PD=at least a 20% increase in the sum of diameter of all target lesions.
Time Frame
From start date to date of first documentation of progression or death (assessed up to 12 months)
Title
Overall Survival (OS)
Description
Overall survival is the time from date of first treatment to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the last date of contact.
Time Frame
From start date to date of death (assessed up to 24 months)
Title
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)
Description
An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
Time Frame
From the signing of the informed consent until 28 days after the last dose of study medication up to 14 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men or women at least 18 years of age with histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease.
Most recent tumor biopsy or surgical resection specimen must be either estrogen-receptor (ER) positive, progesterone receptors (PgR) positive, or both, as defined by immunohistochemistry (IHC) ≥1% (as per the American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines).
HER2-low breast cancer defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested). (as per the ASCO-CAP guidelines).
Postmenopausal status or receiving ovarian ablation with a GnRH agonist such as goserelin. Postmenopausal status is defined by any one of the following criteria:
Prior bilateral oophorectomy.
Age ≥60 years.
Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH, LH, and estradiol in the postmenopausal range per local normal If the patient does not meet criteria for postmenopausal status but is receiving ovarian ablation therapy with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin, the patient is eligible for this study, provided that the GnRH agonist is started at least 2 weeks prior to C1D1 of anti-estrogen therapy.
Patient must have either measurable disease by RECIST 1.1 or only bone lesions in absence of measurable disease.
Eastern Cooperative Group (ECOG) performance status of 0 or 1.
Previously treated on CDK 4/6 inhibitor(palbociclib, abemaciclib or ribociclib) with AI for at least 6 months
Adequate bone marrow and organ function.
Exclusion Criteria:
Patient with symptomatic visceral disease or any disease burden.
Patient has received more than one line of chemotherapy for advanced disease.
Previous treatment with Dalpiciclib /Pyrotinib /ADCe for advanced disease.
Progressed on more than one CDK 4/6 inhibitor
Patients with persistent symptoms and unstable brain metastases;
Any condition that makes the patient ineligible for endocrine therapy per the investigator's best judgment
Facility Information:
Facility Name
Tianjin Cancer Hospital
City
Tianjin
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Dalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy
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