Clinical trial · Interventional

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

A Phase II Clinical Study of Sacituzumab Govitecan Combined With Head Radiotherapy for the Treatment of Brain Metastases From Her2-negative Breast Cancer

NCT06462079CI-TRIAL-00078012not yet recruitingPhase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Brain Metastasis	—	UNRESOLVED	—

Interventions

Interventions (2)

Intervention	Type	Mapped drug	Match
Radiotherapy	Radiation	—	UNRESOLVED
Sacituzumab Govitecan	Drug	Sacituzumab Govitecan	ALIAS

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Group
description
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.
interventionNames
1. Drug: Sacituzumab Govitecan
2. Radiation: Radiotherapy

Primary outcomes (1)

measure
1-year CNS progression-free survival (NPFS)
timeFrame
From the time patients receive this treatment until the next 1 year
description
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.

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 75 Years

Show eligibility criteria text

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.

References

Publications (5)

BACKGROUNDTarantino 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. PMID 34767258
BACKGROUNDOcean 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. PMID 28558150
BACKGROUNDRugo 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. PMID 37633306
BACKGROUNDBardia 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. PMID 33882206
BACKGROUNDXu 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.