Trastuzumab Deruxtecan With or Without Neratinib for HER2-positive Unresectable and/or Metastatic Breast Cancer With Brain Metastasis: A Multicenter, Randomized, Open Label, Phase II Trial (THUNDER Trial)
A phase II, open-label, multicenter, randomized controlled trial exploring the efficacy and safety of Trastuzumab Deruxtecan combined with or without Neratinib in HER2-positive breast cancer with brain metastasis
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• Participants must meet all of the following inclusion criteria in order to be enrolled in this study:
• Female, aged 18-70 years old.
• ECOG score ranges from 0 to 1.
• Expected survival period is greater than 12 weeks.
• Histologically confirmed invasive HER2 positive breast cancer (HER2 IHC+++or FISH/CISH positive, all samples need to be verified by the pathology department of the research center).
• Tumor staging: recurrent or metastatic breast cancer; Patients with local recurrence need to be confirmed by the researcher that radical surgical resection cannot be performed.
• The subject has at least one lesion (measurable and/or unmeasurable) that has not received radiation therapy in the past.
• MRI or CT shows brain metastasis and meets one of the following conditions:
• i) Untreated brain parenchymal metastases detected through imaging screening;
• Ii) Stable or progressive brain parenchymal metastases that have undergone previous local treatment and meet one of the following conditions:
‣ Stable imaging for ≥ 4 weeks;
‣ New brain parenchymal metastases detected by MR or CT.
• Transfer treatment ≤ 2 lines, and did not receive T-DXd or nalatinib.
• The main organ functions are basically normal, meeting the following conditions:
∙ The standard for blood routine examination should meet: HB ≥ 90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L；PLT≥75×109/L；
‣ Biochemical tests must meet the following standards: TBIL ≤ 1.5 × ULN (upper limit of normal value); ALT and AST ≤ 3 × ULN; If there is liver metastasis, ALT and AST should be ≤ 5 × ULN; Serum Cr ≤ 1.5 × ULN, endogenous creatinine clearance rate ≥ 30mL/min (Cockcroft Gault formula).
⁃ Prior to enrollment, the use of mannitol and hormone therapy is allowed, but the medication dosage should be stable for at least one week without the need for an increase.
⁃ Female participants with fertility agreed to take effective contraceptive measures until 3 months after the last use of medication.
⁃ The subjects voluntarily joined this study, signed informed consent forms, had good compliance, and cooperated with follow-up.