Trial Title:
The Efficacy and Safety of Eutideron, Etoposide, and Bevacizumab in Patients With Brain Metastases From Breast Cancer.
NCT ID:
NCT05781633
Condition:
Mammary Neoplasms, Human
Conditions: Official terms:
Brain Neoplasms
Mammary Neoplasms, Animal
Breast Neoplasms
Bevacizumab
Etoposide
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
eutidrone etoposide bevacizumab
Description:
Eligible patients received a regimen of eutidrone(30mg/m2/d,iv,d1-5,21d/cycle),
etoposide(30mg/m2/d,iv,d1-3,21d/cycle), and bevacizumab (10mg/kg,d1,21d/cycle).At least 4
to 6 cycles were administered, and if patients had a response or stable disease,
bevacizumab was used as maintenance therapy until disease progression or intolerable
toxicity.MRI of the brain with contrast enhancement was performed at baseline and every 6
weeks after enrollment; thereafter, patients with stable disease or a response could be
assessed at a reduced frequency to every 9 weeks; central nervous system and noncentral
nervous system lesions were assessed according to RANO-BM criteria and RECIST v1.1
criteria until disease progression, respectively.
Arm group label:
eutidrone+ etoposide+ bevacizumab
Summary:
This study was a single-arm, open-label, phase II study of breast cancer patients with
brain metastases. Eligible patients received a regimen of
eutidrone(30mg/m2/d,iv,d1-5,21d/cycle), etoposide(30mg/m2/d,iv,d1-3,21d/cycle), and
bevacizumab (10mg/kg,d1,21d/cycle).At least 4 to 6 cycles were administered, and if
patients had a response or stable disease, bevacizumab was used as maintenance therapy
until disease progression or intolerable toxicity.
Detailed description:
The natural survival time of breast cancer patients with brain metastases is short and
the prognosis is poor. Although the treatment is progressing, but it is still limited.
The current domestic guidelines still recommend local therapy as a priority treatment
strategy. At the same time, about 80% of patients with brain metastasis will progress to
extracranial metastasis, so superior systemic treatment is particularly important, but
very lacking.Therefore, new systematic therapeutic drugs are urgently needed .Eutiderone
is a new generation of epirubicin anti-tumor drug with good efficacy and safety. In
pre-clinical studies, it has been shown that the drug concentration in most tissues is
higher than that in plasma, and the concentration of eutiderone in brain tissue is
higher, indicating that the drug is easy to cross the blood-brain barrier.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Signed informed consent form.
- Female,>18.
- Histologically or cytologically confirmed recurrent metastatic breast cancer.
- ECOG:0-2.
- There was at least one measurable lesion in the central nervous system.
- Based on screening brain magnetic resonance imaging (MRI), patients with CNS must
meet one of the following conditions：
- Untreated brain metastases from breast cancer do not require immediate local
treatment.
- Previously treated breast cancer brain metastases that have progressed after
previous central nervous system local treatment as assessed by the investigator and
that do not have clinical features requiring immediate local treatment.
- Previous anti-HER2 therapy and TKI therapy were required for HER2+ patients.
- Patients who had not received chemotherapy, radiotherapy, surgery, targeted therapy
or immunotherapy within 4 weeks before enrollment.
- All toxicity in patients associated with previous antitumor therapy must be restored
to ≤ grade 1 (CTCAE v5.0). However, patients with any grade of alopecia were
allowed.
- Routine blood tests were normal within 1 week before enrollment (according to the
normal range at the participating laboratory):White blood cell count (WBC) ≥ 3.0 ×
109/L; Neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 100 × 109/L;
Hemoglobin ≥ 9.0 g/dL; patients could receive blood transfusions or erythropoietin
to meet this criterion.
- Liver and kidney function were basically normal within 1 week before enrollment
(based on the normal values of the participating laboratory):Total bilirubin (TBIL)
≤ 2.5× upper limit of normal value (ULN); Alanine aminotransferase (SGPT/ALT)
≤2.5×ULN (≤5×ULN in patients with liver metastases); Aspartate aminotransferase
(SGOT/AST) ≤2.5×ULN (≤5×ULN in patients with liver metastases); Creatinine clearance
(Ccr) ≥60 ml/min
- Male or female patients of childbearing potential had to consent to use an effective
method of contraception, such as dual barrier methods, condoms, oral or injectable
contraceptives, intrauterine devices, etc., during the study period and up to 90
days after the last study medication was taken. Female patients of reproductive age
had to have a negative blood or urine pregnancy test before enrollment.
- Life expectancy ≥ 12 weeks.
Exclusion Criteria:
- Other malignant tumors (including primary brain or leptomeningeal related tumors)
within the past 5 years, except cured basal cell carcinoma of the skin and carcinoma
in situ of the cervix;
- Previous anti-tumor therapy, including chemotherapy, radical radiotherapy, hormone
therapy, biological therapy, immunotherapy or anti-tumor traditional Chinese
medicine therapy within 4 weeks before initiation of study treatment.
- Patients had previously used eutidrone injection, etoposide, or bevacizumab.
- Patients had undergone major organ surgery (excluding needle biopsies) or major
trauma within 4 weeks before the first dose of the study drug, or required elective
surgery during the trial.
- Patients with ≥grade 3 neurosystem-related severe adverse reactions after previous
use of anti-microtubules.
- Patients with any untreated > 2.0cm brain injury, unless discussed with the
investigator and approved for registration.
- Systemic corticosteroids were continued to control symptoms of brain metastases at a
total daily dose of >2mg dexamethasone (or equivalent). However, patients with
chronic stable doses ≤2mg daily of dexamethasone (or equivalent) may be discussed
and approved by the investigator.
- Any brain lesion deemed to require immediate local treatment, including (but not
limited ) increased lesion size at anatomical sites or possible treatment-related
edema, may pose a risk to the patient (e.g.brain stem lesions). Patients received
local treatment were still eligible for study based on lesions identified by
screening contrast brain MRI according to the criteria described in the CNS
inclusion criteria.
- More than 2 seizures within 4 weeks before enrollment.
- Poor control of hypertension; Or a previous history of hypertensive crisis or
hypertensive encephalopathy.
- Patients had a history of hemoptysis within 6 months before enrollment. Or evidence
of bleeding tendency or significant coagulopathy within the past 1 month.
- Currently receiving full-dose warfarin or equivalent, or aspirin (325mg/ day) within
10 days
- The need for major surgery, open biopsy, or major trauma was anticipated within 28
days or during the course of the study.
- Patients with a history of abdominal fistula or gastrointestinal perforation within
the previous 6 months; The presence of an unhealed wound, active ulcer, or untreated
fracture; Pregnant or lactating women.
- Patients with a history of psychotropic drug abuse and inability to abstain or with
mental disorders.
- Other nonmalignant systemic diseases (cardiovascular, renal, liver, etc.) that were
treated by any treatment regimen or prevented follow-up were excluded.
- Known or suspected allergies to any of the study drugs or excipients.
- No brain MRI for any reason.
- Any other condition considered by the investigator to be unsuitable for
participation in the trial.
- Other situations in which corticosteroid use is prohibited.
Gender:
Female
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Yehui Shi
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Recruiting
Contact:
Last name:
Yehui Shi
Phone:
18622221183
Email:
shiyehui@tjmuch.com
Start date:
July 20, 2022
Completion date:
July 20, 2025
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05781633
