A Phase II Observational Clinical Study on the Relationship Between Cerebrospinal Fluid Drug Concentration and Efficacy of Trastuzumab Deruxtecan in Central Nervous System Metastatic Breast Cancer

NCT07653893 | Recruiting

• 1 other identifier: BCBM-006
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Approximately 5-15% breast cancer patients develop brain metastases. Current local treatments (surgery/radiotherapy) are associated with significant complications, and systemic treatments have limited efficacy. Although new-generation ADC drugs, such as trastuzumab deruxtecan, have demonstrated breakthrough efficacy in patients with brain metastases, the mechanisms of action are not fully elucidated, moreover the current treatment regimens still have limitations for patients with HER2-low expressing, safer and more effective systemic treatment options are urgently needed to improve patient survival. BCBM-006 is an open-label, prospective, single-arm, single-center Phase II clinical study to evaluate the relationship between cerebrospinal fluid drug concentration and efficacy of trastuzumab deruxtecan in central nervous system metastatic breast cancer, and explore the incidence of leptomeningeal metastases diagnosed via lumbar puncture in patients with brain parenchymal metastases, facilitate early intervention to improve prognosis.

Conditions

Central Nervous System (CNS) Metastases; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Correlation between cerebrospinal fluid trastuzumab deruxtecan concentration and intracranial objective response

  Spearman correlation coefficient between cerebrospinal fluid trastuzumab deruxtecan concentration (ng/mL), measured by iquid chromatography-tandem mass spectrometry (LC-MS/MS), and intracranial objective response assessed according to RANO-BM criteria.

  Cerebrospinal fluid samples will be collected at baseline, 6 hours after initiation of trastuzumab deruxtecan infusion, and at disease progression. Intracranial efficacy will be assessed up to 24 months.

Secondary Outcomes (11)

• Objective Response Rate (ORR)

  Assessed up to 24 months.

• Intracranial Objective Response Rate (CNS-ORR)

  Assessed up to 24 months.

• Clinical Benefit Rate (CBR)

  Assessed up to 24 months.

• Intracranial Clinical Benefit Rate (CNS-CBR)

  Assessed up to 24 months.

• Progression-Free Survival (PFS)

  From first dose until disease progression or death from any cause, assessed up to 24 months.

Other Outcomes (2)

• Frequency of genomic alterations associated with intracranial efficacy

  Baseline, 6 hours after initiation of trastuzumab deruxtecan infusion, and at disease progression, assessed up to 24 months.

• Correlation between HER2 expression level and cerebrospinal fluid trastuzumab deruxtecan concentration

  Baseline, 6 hours after initiation of trastuzumab deruxtecan infusion, and at disease progression, assessed up to 24 months.

Study Arms (2)

Cohort 1 : Patients with recurrent metastatic breast cancer without central nervous system metastase

(Control Cohort, N=10)

Other: No Interventions

Cohort 2: Patients with breast cancer and central nervous system metastases

(Experimental Cohort, N=30-50)

Other: No Interventions

Interventions

No Interventions OTHER

no interventions

Cohort 1 : Patients with recurrent metastatic breast cancer without central nervous system metastase; Cohort 2: Patients with breast cancer and central nervous system metastases

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consisted of patients with recurrent metastatic breast cancer, divided into a control cohort without central nervous system metastases (N=10) and an experimental cohort with central nervous system metastases (N=30-50). Ptients in China

You may qualify if:

• \. ≥18 years（2007-06）, any gender. 2. ECOG Performance Status 0-2. 3. Evidence of local recurrence or metastatic breast cancer not amenable to curative surgery or radiotherapy, and planned for intravenous trastuzumab deruxtecan treatment.
• \. Expected survival time ≥8 weeks. 5. Provision of sufficient fresh tissue specimen or ≥10 unstained slides of tumor sample (primary and/or metastatic site) for biomarker analysis prior to treatment (intracranial metastatic lesion specimens preferred).
• \. Cohort 2 (Experimental Cohort): Presence of brain parenchymal metastases confirmed by contrast-enhanced brain MRI, with at least one measurable brain lesion not previously irradiated, evaluable per RECIST 1.1 criteria.
• \. Patients receiving mannitol, steroids, or anticonvulsant therapy prior to the first dose are eligible if the drug doses are stable for at least one week without requiring an increase, and neurological symptoms are stable for ≥1 week.
• \. Organ function levels must meet the following requirements:
• Hematology:
• ANC≥1.5×109/L;
• PLT≥75×109/L;
• Hb≥90 g/L (allowing blood transfusion or medication to ensure hemoglobin content);
• Coagulation function: APTT≤1.5×ULN；PT≤1.5×ULN;
• Blood Chemistry:
• TBIL≤1.5×ULN;
• ALT and AST≤3×ULN (≤ 5.0×ULN for liver metastases);
• Creatinine ≤1.5 × ULN or Creatinine Clearance ≥50 mL/min (Cockcroft-Gault formula);
• Cardiac Ultrasound: LVEF ≥50%;

You may not qualify if:

• \. Presence of uncontrolled third-space fluid accumulation (e.g., large pleural effusion or ascites) not manageable by drainage or other methods, deemed unsuitable for enrollment by the investigator.
• \. Previous treatment with an anti-HER2 ADC drug carrying the same payload resulting in resistance. Patients who discontinued prior ADC therapy for other reasons, including but not limited to toxicity, are eligible.
• \. Adverse reactions from prior anti-tumor therapy have not recovered to ≤ Grade 1 per CTCAE v5.0 (except for ≤ Grade 2 toxicities judged by the investigator as having no safety risk, such as alopecia or long-term toxicities from radiotherapy).
• \. History of other malignancies within the past 5 years, excluding cured carcinoma in situ of the cervix, basocellular skin carcinomas, or cutaneous squamous cell carcinoma.
• \. History of severe cardiovascular or cerebrovascular diseases, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities requiring clinical intervention, such as ventricular arrhythmia, II-III degree atrioventricular block, etc.
• Cardiac insufficiency of Class III\~IV according to the New York Heart Association (NYHA) criteria.
• Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular/cerebrovascular events within 6 months prior to the first dose.
• Clinically uncontrolled hypertension.
• Any factors increasing the risk of QTc prolongation or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, use of any concomitant medications known or suspected to prolong the QT interval; Known history of allergy to any component of the study drug.
• \. History of immunodeficiency disease, including other acquired or congenital immunodeficiency diseases, history of organ transplantation, allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation.
• \. HIV infection, active HBV or HCV infection. The following exceptions are allowed:
• Patients positive for hepatitis B surface antigen (HBsAg), with or without positive hepatitis B core antibody (anti-HBc), if HBV DNA \< 1000 IU/mL or below the lower limit of detection at the research center, and per investigator assessment excluding active infection based on clinical treatment and presentation.
• Hepatitis C (HCV) antibody-positive patients who are HCV RNA-negative. 8. History of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, or glomerulonephritis, except for autoimmune thyroid dysfunction treated with stable-dose hormone replacement therapy.
• \. Patients with known idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, interstitial lung disease, severe radiation pneumonitis, or evidence of active pneumonia on screening chest CT scan.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 28 Days
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief phisician

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: June 17, 2026
• Study Start: June 11, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 17, 2026

Record last verified: 2026-06

Locations

CN (1)