Bevacizumab With Etoposide and Cisplatin in Breast Cancer Patients With Brain and/or Leptomeningeal Metastasis

NCT01281696 | Completed Phase 2 DMC

• 1 other identifier: 201010077M
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to investigate the efficacy of bevacizumab, etoposide and cisplatin in treating breast cancer patients with central nervous system metastasis (including brain parenchymal and leptomeningeal metastasis).

Conditions

Breast Neoplasms; Leptomeningeal Metastasis; Brain Metastases

Keywords

Breast cancer; CNS metastasis; Brain metastasis; Leptomeningeal metastasis; Bevacizumab; Etoposide; Cisplatin

Outcome Measures

Primary Outcomes (1)

• Response rate of central nervous system (CNS) metastasis

  The response criteria for brain parenchymal metastasis is measured according to the volumetric response criteria with modification. CNS lesion(s) which have a ≧ 50% volumetric reduction of in the absence of progressive neurologic signs and symptoms will be considered as responsive. The response criteria for leptomeningeal metastasis is defined as disappearance of carcinoma cells of three consecutive cytology examination of cerebrospinal fluid (CSF) after chemotherapy. For patients with both brain and leptomeningeal metastases, both criteria need to be met to be considered as responsive.

  1 year

Secondary Outcomes (9)

• Number of participants with adverse events

  Baseline to until one month after last course of chemotherapy protocol treatment

• To evaluate the response rate of breast cancer patients with brain parenchymal metastasis after receiving B-EP

  1 year

• To evaluate the response rate of breast cancer patients with leptomeningeal carcinomatosis after receiving B-EP

  1 year

• To evaluate the response rate of extra-CNS lesions according to RECIST

  1 year

• Vascular activity of brain metastatic tumors after bevacizumab treatment

  4 weeks

Study Arms (1)

Bevacizumab, etoposide, cisplatin (BEEP)

EXPERIMENTAL

Drug: Bevacizumab, etoposide, cisplatin; Drug: Intrathecal methotrexate

Interventions

Bevacizumab, etoposide, cisplatin DRUG

Bevacizumab (15mg/kg) on D1, etoposide (70mg/m2) on D2-D4, cisplatin (70mg/m2) on D2; 21 days a cycle, for a maximum of 6 cycles

Also known as: Bevacizumab (Avastin)

Bevacizumab, etoposide, cisplatin (BEEP)

Intrathecal methotrexate DRUG

Additional intrathecal methotrexate only given in patients with leptomeningeal metastasis

Also known as: Methotrexate

Bevacizumab, etoposide, cisplatin (BEEP)

Eligibility Criteria

• Age: 18 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
• Patient with at least one measurable brain metastatic tumor (≧10mm on T1-weighted gadolinium enhanced MRI or contrast-enhanced CT) or leptomeningeal metastasis with positive CSF cytology study.
• Patient whose brain parenchymal metastatic tumors either progress after WBRT, develop new lesions after WBRT, or CNS metastatic tumor do not response to WBRT according to image study 3 months after treatment. Patients with leptomeningeal metastasis does not necessarily need whole brain radiotherapy before enrollment.
• Patients with Her2/neu overexpression or amplification will be allowed but will be informed about other available treatment options such as lapatinib plus capecitabine.
• Patients must have adequate organ and marrow reserve measured within 14 days prior to randomization as defined below:
• Absolute neutrophil count ≧1,000/mcL
• Platelets ≧75,000/mcL
• Total bilirubin ≦ 1.5 X upper normal limit
• AST(SGOT)/ALT(SGPT) ≦ 2.5 X upper normal limit; for patients with liver metastases AST(SGOT)/ALT(SGPT) ≦ 5 X is allowed
• Serum creatinine ≦ upper normal limit or creatinine clearance ≧50ml/min
• Hemoglobin≧8.0 gm/dL
• PTT ≦ upper normal limit; INR ≦ 1.5
• Proteinuria ≤ 1+, if \> 1+, urine protein must be ≦ 1 g/24 hours
• Patient age 18 to 75 years
• Patient's life expectancy is more than 2 months

You may not qualify if:

• Prior therapy with bevacizumab, sorafenib, sunitinib, or other VEGF pathway-targeted therapy
• Patients whose CNS metastasis progressed or developed during prior cisplatin treatment
• 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
• 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 disease
• Arterial thromboembolic event within the past 6 months, including transient ischemic attack, cerebrovascular accident, unstable angina, or myocardial infarction
• History of gross hemoptysis (i.e. ≥ 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

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Taipei Veterans General Hospital, Taiwan: collaborator
• Taichung Veterans General Hospital: collaborator
• Chang Gung Memorial Hospital: collaborator

Study Sites (1)

Department of Oncology, National Taiwan University Hospital

Taipei, Taipei City, 100, Taiwan

Location

Related Publications (2)

• Chen BB, Lu YS, Lin CH, Chen WW, Wu PF, Hsu CY, Yu CW, Wei SY, Cheng AL, Shih TT. A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer. BMC Cancer. 2016 Jul 13;16:466. doi: 10.1186/s12885-016-2494-8.

  PMID: 27412562 DERIVED

• Wu PF, Lin CH, Kuo CH, Chen WW, Yeh DC, Liao HW, Huang SM, Cheng AL, Lu YS. A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis. BMC Cancer. 2015 Apr 17;15:299. doi: 10.1186/s12885-015-1290-1.

  PMID: 25928457 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Meningeal Carcinomatosis; Brain Neoplasms

Interventions

Bevacizumab; Etoposide; Cisplatin; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Brain Diseases; Central 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; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Yen-Shen Lu, MD, PhD

  Department of Oncology, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 24, 2010
• First Posted: January 24, 2011
• Study Start: January 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 16, 2013

Record last verified: 2013-10

Locations

TW (1)