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

Brain Metastasis Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06462079
• Other study ID #: 2024-KY-028-01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 15, 2024
• Est. completion date: July 15, 2027

Study information

• Verified date: June 2024
• Source: Guangzhou Medical University
• Contact: Zhenyu Pan
• Phone: +8618718178286
• Email: dr-zypan[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 43
• Est. completion date: July 15, 2027
• Est. primary completion date: January 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Metastasis
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

Drug:
• 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.

Radiation:
• Radiotherapy
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Medical University

References & Publications (5)

Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortes J, O'Shaughnessy J, Dieras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi: 10.1056/NEJMoa2028485. — View Citation

Ocean AJ, Starodub AN, Bardia A, Vahdat LT, Isakoff SJ, Guarino M, Messersmith WA, Picozzi VJ, Mayer IA, Wegener WA, Maliakal P, Govindan SV, Sharkey RM, Goldenberg DM. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Cancer. 2017 Oct 1;123(19):3843-3854. doi: 10.1002/cncr.30789. Epub 2017 May 30. — View Citation

Rugo HS, Bardia A, Marme F, Cortes J, Schmid P, Loirat D, Tredan O, Ciruelos E, Dalenc F, Gomez Pardo P, Jhaveri KL, Delaney R, Valdez T, Wang H, Motwani M, Yoon OK, Verret W, Tolaney SM. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023 Oct 21;402(10411):1423-1433. doi: 10.1016/S0140-6736(23)01245-X. Epub 2023 Aug 23. — View Citation

Tarantino P, Carmagnani Pestana R, Corti C, Modi S, Bardia A, Tolaney SM, Cortes J, Soria JC, Curigliano G. Antibody-drug conjugates: Smart chemotherapy delivery across tumor histologies. CA Cancer J Clin. 2022 Mar;72(2):165-182. doi: 10.3322/caac.21705. Epub 2021 Nov 12. — View Citation

Xu B, Ma F, Wang T, Wang S, Tong Z, Li W, Wu X, Wang X, Sun T, Pan Y, Yao H, Wang X, Luo T, Yang J, Zeng X, Zhao W, Cong XJ, Chen J. A Phase IIb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments. Int J Cancer. 2023 May 15;152(10):2134-2144. doi: 10.1002/ijc.34424. Epub 2023 Jan 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year CNS progression-free survival (NPFS)	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.	From the time patients receive this treatment until the next 1 year
Secondary	Intracranial objective remission rate (IORR)	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	Assessed at 2 months after the end of treatment or at the time of patient death
Secondary	Rate of new intracranial lesions	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.	Assessed 2 months after the end of treatment or at the time of patient's death
Secondary	Overall progression-free survival (PFS)	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).	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.
Secondary	Overall survival	Survival time was recorded from the date of patient enrollment. All patients were followed until death or the end of the study.	Assessments were performed at least 7 months after diagnosis of brain metastases or before death
Secondary	Incidence of Treatment-Related Adverse Events	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.	Assessments were performed 2 months after the end of treatment or at the time of the patient's death