Clinical trial NCT06462079: Sacituzumab Govitecan Combined With Head Radiotherapy for Her2-negative Breast Cancer Brain Metastases
Official title: A Phase II Clinical Study of Sacituzumab Govitecan Combined With Head Radiotherapy for the Treatment of Brain Metastases From Her2-negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Brain Metastasis
Keywords: Breast cancer
Her2- (Human Epidermal Growth Factor Receptor 2 Negative)
Brain metastasis
Sacituzumab Govitecan
Radiation therapy
Lead sponsor: Guangzhou Medical University
Sponsor class: OTHER
First posted: 2024-06-17
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The incidence of brain metastasis of Her2-negative breast cancer is high, which seriously affects the prognosis of patients.The treatment of brain metastasis of Her2-negative breast cancer is still tricky. The local efficacy of head radiotherapy for breast cancer brain metastases is remarkable, and systemic tumor progression in patients with brain metastases is the main reason for treatment failure. Sacituzumab Govitecan is the only Trop-2 antibody-coupled drug (ADC) approved for the treatment of unresectable locally advanced or metastatic Her2-negative breast cancer. However, the objective remission rate of Sacituzumab Govitecan for intracranial metastatic lesions has not been satisfactory. This study is an open, uncontrolled phase II clinical study to observe the efficacy and safety of Sacituzumab Govitecan combined with intracranial radiotherapy in the treatment of patients with brain metastases from Her2-negative breast cancer, in order to find a more effective treatment method.

Detailed description: This study is a single-arm open phase II clinical trial. It aims to observe the effectiveness and safety of Sacituzumab Govitecan combined with head radiotherapy in the treatment of Her2-negative breast cancer brain metastases, and to search for a more effective treatment option for Her2-negative breast cancer brain metastases. Patients were treated with Sacituzumab Govitecan 10mg/kg every 21 days as a treatment cycle, which was infused intravenously on day 1 and day 8, and the treatment was continued until the disease progressed or unacceptable toxicity occurred. Radiotherapy was administered after the second infusion of Sacituzumab Govitecan, on day 9 after the start of this regimen. The radiotherapy regimen was: brain metastases at a dose of 60 Gy/20 doses. For lesions located adjacent to the brainstem and optic nerve, 54 Gy/20 doses were given. For patients with ≥5 lesions, whole-brain radiotherapy at 40 Gy/20 doses was synchronized with radiotherapy to localized brain metastases.

Eligibility criteria: Inclusion Criteria:

1. Have a definitive pathologic diagnosis of breast cancer with subtype Her2- (including IHC 0, IHC 1+ or IHC 2+ and ISH negative);
2. Have a measurable intracranial lesion;
3. Age ≥ 18 years;

Exclusion Criteria:

1. Patients with cerebrospinal membrane metastases;
2. Patients with acute/subacute hemorrhagic metastasis;
3. Inadequate organ function: 1) Blood tests: ANC ≤ 1.5 x 10\^9/L, PLT ≤ 90 x 10\^9/L, Hb ≤ 90g/L; 2) Blood biochemistry tests: TBIL ≥ 1.5 times the upper limit of normal; 3) ALT and AST ≥ 2.5 times the upper limit of normal;
4. Presence of serious and/or uncontrolled comorbidities that may affect participation: 1) allergy to study medications or adjuvant materials; 2) history of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiency diseases; 3) serious concomitant illnesses;
5. Pregnant and lactating female patients; female patients of childbearing age who are unwilling to use effective contraception during the trial period;
6. Patients who are unable to complete enhanced contrast MRI;
7. Patients who have been treated with Sacituzumab Govitecan and are resistant to the drug;
8. Any other condition that, in the opinion of the investigator, makes the patient ineligible for study participation.

Primary outcomes:
measure: 1-year CNS progression-free survival (NPFS)
timeFrame: From the time patients receive this treatment until the next 1 year
Secondary outcomes:
measure: Intracranial objective remission rate (IORR)
timeFrame: Assessed at 2 months after the end of treatment or at the time of patient death
measure: Rate of new intracranial lesions
timeFrame: Assessed 2 months after the end of treatment or at the time of patient's death
measure: Overall progression-free survival (PFS)
timeFrame: All patients received at least 6 months of follow-up, and NPFS was assessed from the start of treatment to the date of the first documented progression of an extracranial lesion or the date of death from any cause, whichever came first.
measure: Overall survival
timeFrame: Assessments were performed at least 7 months after diagnosis of brain metastases or before death
measure: Incidence of Treatment-Related Adverse Events
timeFrame: Assessments were performed 2 months after the end of treatment or at the time of the patient's death
Other outcomes:
Locations:
Study officials:
affiliation: Huizhou Hospital of Guangzhou Medical University
name: Zhenyu Pan
role: PRINCIPAL_INVESTIGATOR
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