A Phase II Study of T-DXd Plus SRT in HER2-positive Breast Cancer Brain Metastases

NCT ID: NCT06088056

Last Updated: 2023-10-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-30
• Study Completion Date: 2026-07-31

Brief Summary

This research study will evaluate the efficacy and safety of stereotactic radiotherapy (SRT) combined with Trastuzumab-Deruxtecan (T-DXd; DS-8201a) in HER2-positive Breast Cancer Patients with newly diagnosed or progressing Brain Metastases.

Conditions

Breast Cancer; Brain Metastases; Radiotherapy

Study Design

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

Study Groups

Combination use of SRT with T-DXd

Radiation therapy SRT will be implemented according to investigator's clinical practice(based on brain metastases number and tumor volume). T-DXd(5.4mg/kg, once per 21 days, initiated within 2 weeks after SRT) will be provided to patients with confirmed HER2 positive breast cancer and brain metastasis until tumor progression, a severe adverse event deemed related to the study drug, or death. All dose adjustments should be based on the most severe toxicity level (CTCAE version 5.0) that occurred. Two doses are allowed to be reduced.

Dose Level 0: 5.4mg/kg Dose Level 1 :4.4mg/kg Dose Level 2: 3.2mg/kg

Group Type: EXPERIMENTAL

Combination use of SRT with T-DXd

Intervention Type: DRUG

Radiation therapy SRT will be implemented according to investigator's clinical practice(based on brain metastases number and tumor volume). T-DXd(5.4mg/kg, once per 21 days, initiated within 2 weeks after SRT) will be provided to patients with confirmed HER2 positive breast cancer and brain metastasis until tumor progression, a severe adverse event deemed related to the study drug, or death. All dose adjustments should be based on the most severe toxicity level (CTCAE version 5.0) that occurred. Two doses are allowed to be reduced.

Dose Level 0: 5.4mg/kg Dose Level 1 :4.4mg/kg Dose Level 2: 3.2mg/kg

Interventions

Combination use of SRT with T-DXd

Radiation therapy SRT will be implemented according to investigator's clinical practice(based on brain metastases number and tumor volume). T-DXd(5.4mg/kg, once per 21 days, initiated within 2 weeks after SRT) will be provided to patients with confirmed HER2 positive breast cancer and brain metastasis until tumor progression, a severe adverse event deemed related to the study drug, or death. All dose adjustments should be based on the most severe toxicity level (CTCAE version 5.0) that occurred. Two doses are allowed to be reduced.

Dose Level 0: 5.4mg/kg Dose Level 1 :4.4mg/kg Dose Level 2: 3.2mg/kg

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Pathologically confirmed HER2 positive advanced breast cancer
• Age>18 years.
• Brain metastases confirmed by enhanced brain MRI. Metastases number less than 15.
• KPS≥70 or KPS ≥60 with neurologic symptoms caused by BM
• Life expectancy of more than 6 months
• Prior therapy of oral dexamethasone not exceeding 16mg/d
• Time interval from prior therapy was more than 2 weeks, and evaluation of adverse events is no more than grade 1.
• Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration):

1. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L

2. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases

3. Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN)

4. LVEF ≥ 50%

5. QTcF < 480 ms

6. INR≤1.5×ULN，APTT≤1.5×ULN

• Signed the informed consent form prior to patient entry

Exclusion Criteria

• Leptomeningeal or hemorrhagic metastases
• Uncontrolled epilepsy
• Severe or uncontrolled disease: severe cardiovascular disease, end-stage renal disease, severe hepatic disease, history of immunodeficiency, including HIV positive, active HBV/HCV or other acquired congenital immunodeficiency disease, or organ transplantation history, active infection, etc.
• History of allergy to treatment regimens
• Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures.
• Inability to complete enhanced MRI
• Not suitable for inclusion for specific reasons judged by sponsor

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

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xiaoli Yu

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhaozhi Yang

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Jiayi Chen

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital affiliated to Shanghai Jiaotong University

Locations

Fudan University Shanghai Cancer Center

Shanghai, , China

Countries

China

Central Contacts

Zhaozhi Yang

Role: CONTACT

yzzhi2014@163.com

+8618017317126

Facility Contacts

Zhaozhi yang, PhD

Role: primary

yzzhi2014@163.com

+8618017317126

Jin Meng, PhD

Role: backup

jinmeng@fudan.edu.cn

+8618121299532

Other Identifiers

FDRT-BC021

Identifier Type: -

Identifier Source: org_study_id