Sacituzumab Govitecan Combined With Head Radiotherapy for Her2-negative Breast Cancer Brain Metastases

Phase 2

Not yet recruiting

• Conditions: Brain Metastasis
• Interventions: Drug: Sacituzumab Govitecan; Radiation: Radiotherapy

• Registration Number: NCT06462079
• Lead Sponsor: Guangzhou Medical University

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.

Study Timeline

• Status Verified: 2024-06
• Study First Submitted: 2024-06-12
• Study First Submitted QC: 2024-06-12
• Last Update Submitted: 2024-06-12
• Study Start: 2024-06-15
• Study First Posted: 2024-06-17
• Last Update Posted: 2024-06-17
• Primary Completion: 2027-01-15
• Study Completion: 2027-07-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 43

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group	Sacituzumab Govitecan	Patients were treated with Sacituzumab Govitecan 10 mg/kg in 21-day treatment cycles with intravenous infusions on days 1 and 8 and continued until disease progression or unacceptable toxicity. 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.
Group	Radiotherapy	Patients were treated with Sacituzumab Govitecan 10 mg/kg in 21-day treatment cycles with intravenous infusions on days 1 and 8 and continued until disease progression or unacceptable toxicity. 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.

Primary Outcome Measures

Name	Time	Method
1-year CNS progression-free survival (NPFS)	From the time patients receive this treatment until the next 1 year	Proportion of patients free of CNS progression at 1 year from the time the patient receives this treatment. Neurological progression was assessed according to the Response Assessment of Neuro-Oncology Brain Metastases (RANO-BM) criteria.

Secondary Outcome Measures

Name	Time	Method
Rate of new intracranial lesions	Assessed 2 months after the end of treatment or at the time of patient's death	The proportion of patients presenting with new brain metastases from the time the patient received treatment. New brain metastases are assessed according to the Response Assessment of Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Incidence of Treatment-Related Adverse Events	Assessments were performed 2 months after the end of treatment or at the time of the patient's death	The incidence of treatment-related adverse events was measured to determine tolerability and safety. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03).Grade 3-5 events were defined as moderate and severe adverse events.
Overall survival	Assessments were performed at least 7 months after diagnosis of brain metastases or before death	Survival time was recorded from the date of patient enrollment. All patients were followed until death or the end of the study.
Overall progression-free survival (PFS)	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.	The time from the time the patient receives this treatment to the time of disease progression or death. Assessment of extracranial lesions follows the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1).
Intracranial objective remission rate (IORR)	Assessed at 2 months after the end of treatment or at the time of patient death	The proportion of patients whose brain metastases shrink in volume to achieve complete remission/partial remission from the time the patient receives this treatment. Complete remission/partial remission is assessed according to the Response Assessment of Neuro-Oncology Brain Metastases (RANO-BM) criteria