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

NCT06088056 | Not Yet Recruiting Phase 2

• 1 other identifier: FDRT-BC021
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Intracranial CNS Progression Free Survival(IC-PFS)

  2 years

• Progression Free Survival(PFS)

  2 years

• Overall survival(OS)

  3 years

• Percentage of Participants With Adverse Events Percentage of Participants With Adverse Events

  2 years

• Health-related quality of life per FACT-BR

  2 years

Study Arms (1)

Combination use of SRT with T-DXd

EXPERIMENTAL

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

Interventions

Combination use of SRT with T-DXd 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

Combination use of SRT with T-DXd

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases
• Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN)
• LVEF ≥ 50%
• QTcF \< 480 ms
• INR≤1.5×ULN，APTT≤1.5×ULN
• Signed the informed consent form prior to patient entry

You may not qualify if:

• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Zhaozhi Yang

  Fudan University

  PRINCIPAL INVESTIGATOR

• Jiayi Chen

  Ruijin Hospital affiliated to Shanghai Jiaotong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhaozhi Yang

CONTACT

+8618017317126; yzzhi2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: July 30, 2023
• First Posted: October 18, 2023
• Study Start: November 1, 2023
• Primary Completion: June 1, 2024
• Study Completion (Estimated): July 1, 2026
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)