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

NCT02185352 | Unknown Phase 2 DMC

• 1 other identifier: 201402059MIPD
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Breast Cancer; Brain Metastases

Keywords

Bevacizumab; Brain Metastases; Breast Cancer; Chemotherapy; Whole Brain Radiotherapy

Outcome Measures

Primary Outcomes (1)

• The Brain-specific progression free survival (BS-PFS)

  To evaluate and compare the brain-specific progression free survival (BS-PFS) of the two treatment arms based on RECIST 1.1.

  2.5 years

Secondary Outcomes (1)

• The 2-month brain-specific objective response rate (BS-ORR)

  2 months

Other Outcomes (8)

• The BS-PFS based on volumetric analysis (CNS composite response criteria)

  2.5 years

• The 8-month BS-PFSR based on volumetric analysis (CNS composite response criteria)

  8 months

• The BS-ORR based on volumetric analysis (CNS composite response criteria)

  5 months

Study Arms (2)

Inductional BEEP regimen

EXPERIMENTAL

Induction BEEP regimen: Every 3 weeks a cycle for a total of 3 cycles (around 2 months) * Bevacizumab 15mg/kg IVF on D1 * Etoposide 70 mg/m2 IVF QD, D2-4 * Cisplatin 70 mg/m2 IVF on D2 WBRT: 3000cGy in 10 fractions

Drug: BEEP regimen

WBRT alone

NO INTERVENTION

standard WBRT: 3000cGy in 10 fractions

Interventions

BEEP regimen DRUG

Bevacizumab 15mg/kg IVF on D1, Etoposide 70 mg/m2 IVF QD, D2-4, Cisplatin 70 mg/m2 IVF on D2, repeat every 3 weeks, for 3 cycles

Also known as: Bevacizumab, Etoposide, Cisplatin

Inductional BEEP regimen

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (8)

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Taiwan

Location

Shuang Ho Hospital

New Taipei City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Tri-Service General Hospital

Taipei, 114, Taiwan

Location

Mackay Memorial Hospital

Taipei, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital-LinKou

Taoyuan District, Taiwan

Location

Related Publications (1)

• Chen TW, Dai MS, Tseng LM, Chen SC, Chao TY, Chao TC, Chang YC, Chiu CF, Liu CT, Lin CH, Liu CY, Chen YF, Chang DY, Yu JC, Rau KM, Hsieh YY, Shen SC, Huang SM, Cheng AL, Lu YS. Whole-Brain Radiotherapy Alone vs Preceded by Bevacizumab, Etoposide, and Cisplatin for Untreated Brain Metastases From Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2024 Mar 1;10(3):325-334. doi: 10.1001/jamaoncol.2023.5456.

  PMID: 38127335 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

Bevacizumab; Etoposide; Cisplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yen-Shen Lu, M.D, Ph.D.

  National Taiwan Unversity Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: July 9, 2014
• Study Start: April 21, 2014
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2022
• Last Updated: May 7, 2021

Record last verified: 2021-05

Locations

TW (8)