Dalpiciclib Plus Fulvestrant With Pyrotinib in Hormone Receptor-positive, HER2-low Advanced Breast Cancer That Progressed on Previous CDK4/6i Plus AI Therapy

NCT ID: NCT05806671

Last Updated: 2023-04-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-31
• Study Completion Date: 2025-12-31

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dalpiciclib, Fulvestrant With Pyrotinib

Pyrotinib 320mg/day Dalpiciclib 125 mg/day Fulvestrant 500mg

Group Type: EXPERIMENTAL

Dalpiciclib

Intervention Type: DRUG

Dalpiciclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off

Pyrotinib

Intervention Type: DRUG

Pyrotinib 320mg/day orally continuously

Fulvestrant

Intervention Type: DRUG

Fulvestrant 500mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

Interventions

Dalpiciclib

Dalpiciclib 125 mg/day orally continuously dosed for 3 weeks followed by 1 week off

Intervention Type: DRUG

Pyrotinib

Pyrotinib 320mg/day orally continuously

Intervention Type: DRUG

Fulvestrant

Fulvestrant 500mg intramuscularly on Days 1 and 15 of Cycle 1, and then on Day 1 of each subsequent 28 day cycle

Intervention Type: DRUG

Other Intervention Names

SHR6390

Eligibility Criteria

Inclusion Criteria

1. Men or women at least 18 years of age with histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease.

2. 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).

3. HER2-low breast cancer defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested). (as per the ASCO-CAP guidelines).

4. 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.

5. Patient must have either measurable disease by RECIST 1.1 or only bone lesions in absence of measurable disease.

6. Eastern Cooperative Group (ECOG) performance status of 0 or 1.

7. Previously treated on CDK 4/6 inhibitor(palbociclib, abemaciclib or ribociclib) with AI for at least 6 months

8. Adequate bone marrow and organ function.

Exclusion Criteria

1. Patient with symptomatic visceral disease or any disease burden.

2. Patient has received more than one line of chemotherapy for advanced disease.

3. Previous treatment with Dalpiciclib /Pyrotinib /ADCe for advanced disease.

4. Progressed on more than one CDK 4/6 inhibitor

5. Patients with persistent symptoms and unstable brain metastases;

6. Any condition that makes the patient ineligible for endocrine therapy per the investigator's best judgment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tianjin Cancer Hospital

Tianjin, , China

Countries

China

Other Identifiers

OBU-BC-II-086

Identifier Type: -

Identifier Source: org_study_id