Overview

Bevacizumab, Etoposide and Cisplatin Followed by Whole Brain Radiotherapy in Breast Cancer With Brain Metastases

Status:
Active, not recruiting
Trial end date:
2022-11-01
Target enrollment:
0
Participant gender:
Female
Summary
The primary objective of A-PLUS trial is to evaluate and compare the efficacy of induction BEEP (bevacizumab preconditioning followed by etoposide and cisplatin) followed by whole bran radiotherapy (WBRT) with WBRT alone in the controlling of brain metastases (BM) in metastatic breast cancer (MBC) patients who have not previously received WBRT. In past 2 years, the research team has demonstrated that BEEP regimen is a highly effective treatment for brain metastases of breast cancer progressing from WBRT by a multi-center phase II study (ClinicalTrials.gov Identifier: NCT01281696). The basic concept of preconditioning, as referred to starting bevacizumab 1 day before chemotherapy, is that the effect of bevacizumab induced tumor vascular normalization takes time to mature. The investigators hypothesized that as induction BEEP decreased the size of brain tumors, the effectiveness of WBRT would be maximized. The investigators expect this integrated approach will do greater benefit to MBC patients with BM, irrespective of subtype.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Taiwan University Hospital
Treatments:
Bevacizumab
Cisplatin
Etoposide
Etoposide phosphate
Criteria
Inclusion criteria:

- A histological confirmed invasive breast cancer.

- At least one measurable brain metastatic tumor. If the measurable brain lesion has
previously received stereotactic radiosurgery, the tumor must be a progressive lesion
after radiosurgery.

- Patients who had not received WBRT.

- Patients with HER2/neu overexpression or amplification and had received trastuzumab
before the diagnosis of BM will be allowed but will be informed about other available
treatment options such as lapatinib plus capecitabine.

- Karnofsky performance score (KPS) higher or equal to 30%.

- Patients must have adequate organ function and marrow reserve measured within 14 days
prior to randomization

- Age 20 to 75 years.

- Patient's life expectancy is more than 3 months.

- All women of childbearing potential must have a negative pregnancy test obtained
within 72 hours before starting therapy.

- Patients with reproductive potential must use effective contraception (hormone or
barrier method of birth control; abstinence) prior to study entry, for the duration of
study participation, and for 6 months after the completion of therapy.

- Patients (or a surrogate) must be able to comply with study procedures and sign
informed consent.

Exclusion criteria:

- Prior therapy with bevacizumab, sorafenib, sunitinib, or other VEGF pathway-targeted
therapy.

- Patients who have history of disease progression or disease developed during prior
cisplatin treatment.

- Patients who had leptomeningeal metastasis, either diagnosed by brain imaging study or
confirmed by cerebrospinal fluid cytology examination.

- Patients who are eligible for and willing to receive brain surgery or stereotactic
radiosurgery (SRS) as the initial treatment of BM.

- History or evidence of inherited bleeding diathesis or coagulopathy with the risk of
bleeding.

- History of thrombotic disorders.

- Active gastrointestinal bleeding.

- Patients with a history of self-reported intra-cranial hemorrhage or evidence of
bleeding in previous cranial imaging.

- Patients with clinical signs or symptoms of gastrointestinal obstruction and who
require parenteral hydration and/or nutrition because of obstruction.

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 6 months of first dose of bevacizumab.

- Clinically significant peripheral artery occlusive disease.

- Arterial thromboembolic event within the past 6 months, including transient ischemic
attack, cerebrovascular accident, unstable angina, or myocardial infarction.

- History of gross hemoptysis (e.g., ≥ 1 teaspoon of bright red blood).

- Other malignancy within 5 years except cured basal cell or squamous cell skin cancer
or carcinoma in situ of the cervix.

- Psychiatric illness or social situation that would preclude study compliance.

- Serious non-healing wound, ulcer, or bone fracture.

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to enrollment.

- Prior minor surgery within 7 days.

- Concurrent chronic daily aspirin (> 325 mg/day), dipyridamole, ticlopidine,
clopidogrel, cilostazol, non-steroidal anti-inflammatory agents known to inhibit
platelet function.

- Concurrent therapeutic anticoagulation, but prophylactic anti-coagulation of venous
access devices is allowed.

- History of allergic reaction to compounds of similar chemical composition to the study
drugs.

- Pregnancy or lactation.