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

NCT06462079 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2024-KY-028-01
• Study Type: interventional
• Target: 43
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Brain Metastasis

Keywords

Breast cancer; Her2- (Human Epidermal Growth Factor Receptor 2 Negative); Brain metastasis; Sacituzumab Govitecan; Radiation therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Intracranial objective remission rate (IORR)

  Assessed at 2 months after the end of treatment or at the time of patient death

• Rate of new intracranial lesions

  Assessed 2 months after the end of treatment or at the time of patient's death

• 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.

• Overall survival

  Assessments were performed at least 7 months after diagnosis of brain metastases or before death

• 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

Study Arms (1)

Group

EXPERIMENTAL

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.

Drug: Sacituzumab Govitecan; Radiation: Radiotherapy

Interventions

Sacituzumab Govitecan DRUG

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.

Also known as: Trodelvy

Group

Radiotherapy RADIATION

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients with cerebrospinal membrane metastases;
• Patients with acute/subacute hemorrhagic metastasis;
• 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;
• 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;
• Pregnant and lactating female patients; female patients of childbearing age who are unwilling to use effective contraception during the trial period;
• Patients who are unable to complete enhanced contrast MRI;
• Patients who have been treated with Sacituzumab Govitecan and are resistant to the drug;
• Any other condition that, in the opinion of the investigator, makes the patient ineligible for study participation.

Sponsors & Collaborators

• Guangzhou Medical University: lead

Related Publications (5)

• 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.

  PMID: 34767258 BACKGROUND

• 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.

  PMID: 28558150 BACKGROUND

• 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.

  PMID: 37633306 BACKGROUND

• 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.

  PMID: 33882206 BACKGROUND

• 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.

  PMID: 36621000 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms; Breast Neoplasms

Interventions

sacituzumab govitecan; Radiotherapy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Zhenyu Pan

  Huizhou Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenyu Pan

CONTACT

+8618718178286; dr-zypan@163.com

Guozi Yang

CONTACT

+8615804302755; guoziyang_1982@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 12, 2024
• First Posted: June 17, 2024
• Study Start: June 15, 2024
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): July 15, 2027
• Last Updated: June 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Starting 6 months after publication.
• Access Criteria: Individual participant data will be public accessable via contacting with principal investigator by email within 6 months after the trial complete.