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Bevacizumab, Etoposide and Cisplatin Followed by Whole Brain Radiotherapy in Breast Cancer With Brain Metastases (A-Plus)

This study is currently recruiting participants.
Verified January 2017 by National Taiwan University Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT02185352
First Posted: July 9, 2014
Last Update Posted: January 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Taiwan University Hospital
  Purpose

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.


Condition Intervention Phase
Breast Cancer Brain Metastases Drug: BEEP regimen Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Induction Bevacizumab, Etoposide and Cisplatin Followed by Whole Brain Radiotherapy (WBRT) Versus WBRT Alone in Breast Cancer With Untreated Brain Metastases

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • The Brain-specific progression free survival (BS-PFS) [ Time Frame: 2.5 years ]
    To evaluate and compare the brain-specific progression free survival (BS-PFS) of the two treatment arms based on RECIST 1.1.


Secondary Outcome Measures:
  • The 2-month brain-specific objective response rate (BS-ORR) [ Time Frame: 2 months ]
    To compare the 2-month brain-specific objective response rate (BS-ORR) of the two treatment arms based on volumetric analysis (CNS composite response criteria).


Other Outcome Measures:
  • The BS-PFS based on volumetric analysis (CNS composite response criteria) [ Time Frame: 2.5 years ]
    To compare the BS-PFS of the two treatment arms based on volumetric analysis (CNS composite response criteria).

  • The 8-month BS-PFSR based on volumetric analysis (CNS composite response criteria) [ Time Frame: 8 months ]
    To compare the 8-month BS-PFSR of the two treatment arms based on volumetric analysis (CNS composite response criteria).

  • The BS-ORR based on volumetric analysis (CNS composite response criteria) [ Time Frame: 5 months ]
    To evaluate and compare the BS-ORR of the two treatment arms based on volumetric analysis (CNS composite response criteria).

  • The 8-month BS-PFSR based on RECIST 1.1 [ Time Frame: 8 months ]
    To compare the 8-month BS-PFSR of the two treatment arms based on RECIST 1.1.

  • The progression free survival (PFS) and overall survival (OS) [ Time Frame: 2.5 years ]
    To observe the difference of the PFS and OS between the two treatment arms.

  • The extra-CNS tumor progression free survival (PFS) based on RECIST 1.1 [ Time Frame: 2.5 years ]
    To evaluate and compare extra-CNS tumor progression free survival (PFS) of the two treatment arms (and followed by physician/investigator choice of systemic therapy) based on RECIST 1.1.

  • The time-to-improvement of neurological function [ Time Frame: 3 months ]
    To evaluate the difference of time-to-improvement of neurological function between the two treatment arms.

  • Number of participants with adverse events [ Time Frame: 3 months ]
    To evaluate and compare the safety profile of the two treatment arms according CTCAE 4.0.


Estimated Enrollment: 126
Study Start Date: September 2014
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inductional BEEP regimen

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
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
Other Names:
  • Bevacizumab
  • Etoposide
  • Cisplatin
No Intervention: WBRT alone

standard WBRT:

3000cGy in 10 fractions


  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02185352


Contacts
Contact: Yen-Shen Lu, M.D., Ph.D. +886-2-23123456 ext 71673 yslu@ntu.edu.tw

Locations
Taiwan
Kaohsiung Chang Gung Memorial Hospital Recruiting
Kaohsiung, Taiwan
Contact: Kun-Ming Rau, MD    +886-7-7317123 ext 8303    kmrau58@adm.cgmh.org.tw   
Principal Investigator: Kun-Ming Rau, MD         
Shuang Ho Hospital Recruiting
New Taipei City, Taiwan
Contact: Tsu-Yi Chao, MD    +886-2-22490088 ext 8402    10575@shh.org.tw   
Principal Investigator: Tsu-Yi Chao, MD         
China Medical University Hospital Recruiting
Taichung, Taiwan
Contact: Chang-Fang Chiu, MD    +886-4-22052121 ext 1921    d5686@mail.cmuh.org.tw   
Principal Investigator: Chang-Fang Chiu, MD         
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Yen-Shen Lu, MD, PhD    +886-2-23123456 ext 71673    yslu@ntu.edu.tw   
Principal Investigator: Yen-Shen Lu, MD, PhD         
Tri-Service General Hospital Recruiting
Taipei, Taiwan, 114
Contact: Jyh-Cherng Yu, MD    +886-2-89723311 ext 16020    doc20106@ndmctsgh.edu.tw   
Contact: Ming-Shen Dai, MD, PhD    +886-2-89723311 ext 12623    dms1201@gmail.com   
Principal Investigator: Jyh-Cherng Yu, MD         
Mackay Memorial Hospital Active, not recruiting
Taipei, Taiwan
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan
Contact: Ling-Ming Tseng, MD    +886-2-28757535 ext 134    lmtseng@vghtpe.gov.tw   
Contact: Ta-Chung Chao, MD       tcchao@vghtpe.gov.tw   
Principal Investigator: Ling-Ming Tseng, MD         
Chang Gung Memorial Hospital-LinKou Recruiting
Taoyuan, Taiwan
Contact: Shin-Cheh Chen, MD    +886-2-27135211 ext 3141    chensc@adm.cgmh.org.tw   
Principal Investigator: Shin-Cheh Chen, MD         
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Yen-Shen Lu, M.D, Ph.D. National Taiwan Unversity Hospital
  More Information

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02185352     History of Changes
Other Study ID Numbers: 201402059MIPD
First Submitted: June 25, 2014
First Posted: July 9, 2014
Last Update Posted: January 19, 2017
Last Verified: January 2017

Keywords provided by National Taiwan University Hospital:
Bevacizumab
Brain Metastases
Breast Cancer
Chemotherapy
Whole Brain Radiotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Etoposide phosphate
Cisplatin
Bevacizumab
Etoposide
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action