Treatment for brain metastases in triple-negative breast cancer

A Prospective, Single-arm, Single-center, Phase II Clinical Study of Triple-negative Breast Cancer Brain Metastases

This study is testing a new combination treatment for people with triple-negative breast cancer that has spread to the brain to see if it helps them feel better and stay safe.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Fudan University (other)
• Drugs / interventions: bevacizumab, chemotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT04303988 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effectiveness and safety of a combination treatment involving SHR 1316, bevacizumab, and cisplatin/carboplatin for patients with brain metastases from triple-negative breast cancer. The study follows a prospective, single-arm design and will enroll participants who meet specific eligibility criteria, including age and cancer characteristics. Patients will receive the treatment until disease progression, intolerable toxicity, or other specified discontinuation criteria are met, with data collected on drug efficacy and safety.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with confirmed triple-negative breast cancer and MRI-confirmed brain metastases.

Not a fit: Patients who have previously received platinum drugs or those with HER2-positive breast cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with triple-negative breast cancer brain metastases.

How similar studies have performed: Other studies have explored treatments for brain metastases in breast cancer, but this specific combination approach is novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years old, and ≤ 70 years old, both genders;
2. ECOG performance status 0-2;
3. Pathological tests confirm HR-negative / HER2-negative breast cancer; there is evidence of local recurrence or metastasis；not suitable with curative surgery or radiation therapy；HR negative is defined as: ER-negative and PR-negative, the proportion of positively stained tumor cells in all tumor cells is \<1%；HER2- negative is defined as: histologically confirmed to be HER2 IHC (0) or HER2 IHC(1+) or HER2 IHC (2+) and FISH(-);
4. It is required that no platinum drugs have been used before, or platinum drugs have been used (cisplatin/carboplatin only one regimen) and platinum sensitive: no progression during at least 4 cycles of treatment, more than 3 months period between last platinum regimen and the progression of disease；
5. MRI confirmed brain metastases, at least one intracranial parenchymal metastatic lesion with a longest diameter ≥ 1.0 cm without prior radiotherapy；
6. Mannitol or steroid hormone therapy is allowed before enrollment, but the dose of steroid hormone should be stable for at least one week;
7. Adequate function of major organs meets the following requirements:

(1)Blood routine ANC≥1.5×109/L； PLT≥75×109/L； Hb≥90 g/L(Allows blood transfusion or the use of medication to ensure that the content of hemoglobin) (2)Coagulation: INR≤1.5，APTT≤1.5×ULN, PT does not exceed the upper limit of normal (3)Blood biochemistry TBIL≤1.5 × ULN; ALT and AST≤3 × ULN (liver metastasis≤5.0 × ULN); Urea nitrogen ≤ 1.5 × ULN; Cr≤1.5 × ULN or creatinine clearance ≥50 mL / min (Cockcroft-Gault formula) (4)Cardiac ultrasound: LVEF≥50%; (5)12-lead ECG: females QTcF interval \<470msec and males \<450ms; 8.Willing to join the study, sign informed consent, have good compliance and cooperate with follow-up.

Exclusion Criteria:

1. Leptomeningeal or cystic metastases confirmed by MRI or lumbar puncture.
2. Presence of third interstitial fluid that cannot be controlled by drainage or other methods (e.g., a large amount of pleural effusion and ascites);
3. Whole brain radiotherapy, chemotherapy or surgery within 14 days prior to enrollment. Has received prior therapy with Targeted therapy or Endocrine therapy within the previous week；
4. Subjects with HR-/HER2- who has received prior therapy with bevacizumab or PD-1/PD-L1；
5. Participation in any other clinical trials within 2 weeks of enrollment；
6. Concurrent use of any other Anti-cancer drugs；
7. Other malignancies within 5 years, except cured in-situ of uterine cervix carcinoma , skin basal cell carcinoma and squamous-cell carcinoma；
8. History of heart disease: (1) Arrhythmias requiring medical treatment or clinical significance, (2) Myocardial infarction, (3) Heart failure, (4)Any heart diseases that investigator believes not suitable for this study;
9. History of allergy or hypersensitivity to any of the study drugs or study drug components；
10. History of immunodeficiency including HIV-positive, active hepatitis B/C, other acquired, congenital immunodeficiency disease or history of organ transplantation；
11. A clear history of neurological or mental disorders, including epilepsy or dementia；
12. Pregnant or breastfeeding women. Women of childbearing potential who have a positive pregnancy test or unwilling to use adequate contraception prior to enrollment and for the duration of study participation；
13. According to the investigator's judgment, there is a concomitant disease that seriously endangers the safety of subjects or affects the completion of the study (including but not limited to severe hypertension, severe diabetes, active infection, thyroid disease that cannot be controlled by drugs)；
14. Any condition which in the investigator's opinion makes the subjects unsuitable for the study participation.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Jian Zhang, MD — Fudan University
• Study coordinator: Jian Zhang, MD

Conditions: Breast Cancer