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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06088056
• Other study ID #: FDRT-BC021
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 2023
• Est. completion date: July 2026

Study information

• Verified date: October 2023
• Source: Fudan University
• Contact: Zhaozhi Yang
• Phone: +8618017317126
• Email: yzzhi2014[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 17
• Est. completion date: July 2026
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Breast Cancer
• Breast Neoplasms
• Neoplasm Metastasis
• Radiotherapy

Intervention

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

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Overall survival(OS)	Time from the treatment until to the date of death, regardless of the cause of death	3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Neurocognitive function per HVLT-R	Neurocognitive function was evaluated using HVLT-R test	2 years