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.