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

Fudan University

Status and phase: Not yet enrolling; Phase 2

Conditions: Breast Cancer; Brain Metastases; Radiotherapy

Treatments: Drug: Combination use of SRT with T-DXd

Study type: Interventional

Funder types: Other

Identifiers

NCT06088056

FDRT-BC021

Details and patient eligibility

About

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.

Enrollment: 17 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

Combination use of SRT with T-DXd

Experimental group

Description:

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

Treatment:

Drug: Combination use of SRT with T-DXd