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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Brain Metastases; Radiotherapy
• Intervention / Treatment: Drug: Combination use of SRT with T-DXd

• Study Type: Interventional
• Enrollment (Estimated): 17
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhaozhi Yang; Phone Number: +8618017317126; Email: yzzhi2014@163.com

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
    • Contact: Zhaozhi yang, PhD; Phone Number: +8618017317126; Email: yzzhi2014@163.com
    • Principal Investigator: Zhaozhi Yang, PhD
    • Contact: Jin Meng, PhD; Phone Number: +8618121299532; Email: jinmeng@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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

Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial objective response rate(IC-ORR)	Proportion of participants with a complete response (CR) or partial response (PR) for intracranial tumors as defined by response assessment in neuro-oncology brain metastases (RANO-BM) criteria.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial CNS Progression Free Survival(IC-PFS)	Time from treatment until the first date of intracranial disease progression or death due any cause. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment.	2 years
Progression Free Survival(PFS)	Time from treatment until the first date of intracranial or extracranial disease progression or death due any cause. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment.	2 years
Overall survival(OS)	Time from the treatment until to the date of death, regardless of the cause of death	3 years
Percentage of Participants With Adverse Events Percentage of Participants With Adverse Events	Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0	2 years
Health-related quality of life per FACT-BR	Health-related quality of life was evaluated using the QLQ-C30 questionnaires to assess Health-related quality of life was evaluated using the FACT-BR questionnaires to assess the quality of life	2 years
Local control rate	The percentage of participants who have achieved complete response, partial response and stable disease according to RANO-BM criteria after treatment	2 years
Neurocognitive function per HVLT-R	Neurocognitive function was evaluated using HVLT-R test	2 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Zhaozhi Yang, Fudan University; Principal Investigator: Jiayi Chen, Ruijin Hospital affiliated to Shanghai Jiaotong University

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 30, 2023
• First Submitted That Met QC Criteria: October 14, 2023
• First Posted (Actual): October 18, 2023

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 14, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: FDRT-BC021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No