Trial of Paclitaxel/Bevacizumab +/- Everolimus for Patients With HER2-Negative Metastatic Breast Cancer

Completed · Phase 2 · Has a placebo group

Conditions studied: Metastatic Breast Cancer

In brief

This randomized, double blind, placebo controlled trial will evaluate the impact of adding everolimus to the combination of weekly paclitaxel plus bevacizumab in the first-line treatment of women with HER2-negative metastatic breast cancer. Patients will be randomized (1:1) to receive either paclitaxel/bevacizumab/everolimus (Treatment Arm 1) or paclitaxel/ bevacizumab/placebo (Treatment Arm 2). Patients will be evaluated for response to treatment every 8 weeks; responding and/or stable patients will continue treatment, with re-evaluations every 8 weeks, until tumor progression or intolerable toxicity occurs. Outcomes will be assessed for each treatment arm separately. This trial is not intended to compare treatment arms primarily. Any such analyses are exploratory and will be conducted without adjustment for multiple hypothesis testing.

Key facts

Study ID

NCT00915603

Run by

SCRI Development Innovations, LLC

People needed

113

Starts

2009-07-01

Expected to finish

2014-07-01

Last updated by the study team

2014-12-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Female or male patients >=18 years of age.
• Histologically confirmed invasive breast cancer, locally unresectable or metastatic.
• No prior chemotherapy for MBC. Patients may have received adjuvant or
• neoadjuvant chemotherapy (including taxanes and/or bevacizumab) as long as
• treated was completed >12 months prior to relapse. Prior hormonal therapy in the
• adjuvant or metastatic setting will be permitted.
• Prior hormonal therapy in the adjuvant or metastatic setting is permitted. Estrogen receptor positive patients should be considered candidates for chemotherapy.
• HER2-negative breast cancer, defined as follows:
• FISH-negative (FISH ratio <2.2), or
• IHC 0-1+, or
• IHC 2-3+ AND FISH-negative (FISH ratio <2.2).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate hematologic function, defined by:
• · Absolute neutrophil count (ANC) >1500/mm3
• Platelet count >=100,000/mm3
• Hemoglobin >9 g/dL
• Adequate liver function, defined by:
• · AST and ALT <=2.5 x the upper limit of normal (ULN) or <=5 x ULN in
• presence of liver metastases
• Total bilirubin <=1.5 x ULN
• Adequate renal function, defined by:
• · Serum creatinine <=1.5 x ULN or calculated creatinine clearance of
• >=40 ml/min
• International normalized ratio (INR) <=1.5 or prothrombin time (PT)/partial
• thromboplastin time (PTT) within normal limits (WNL) of the institution (if patient is not on anti-coagulation therapy). Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin are eligible if the INR is stable and within the therapeutic range prior to study treatment initiation.

You may not qualify if…

• Patients with active brain metastases or meningeal metastases. Patients who have had brain metastases resected, or have received brain radiation therapy >4 weeks prior to study entry are eligible, if they meet all of the following criteria: 1) residual symptoms < grade 2, 2) no dexamethasone requirement, and 3) follow-up MRI shows regression of lesions after treatment and no new lesions appearing.
• Previous treatment with an m-TOR inhibitor (sirolimus, temsirolimus, everolimus) or anti-angiogenesis agent unless:
• in the adjuvant setting, and
• >=12 months prior to recurrence.
• Previous radiotherapy for metastatic disease completed <2 weeks prior to study treatment initiation.
• Patients who are current receiving systemic cancer therapy or have received
• previous systemic therapy within 4 weeks of the start of study drug (e.g.
• chemotherapy, antibody therapy, targeted agents).
• Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.
• Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or
• diastolic pressure >100 mmHg, despite optimal medical management.
• Concurrent use of CYP3A4 inhibitors and inducers from 72 hours prior to initiation of study treatment until the end of treatment with everolimus.
• Cardiac disease, including: congestive heart failure (CHF) > Class II per New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• History of stroke or transient ischemic attack within 6 months prior to first
• bevacizumab dose.
• Patients with any non-healing wound, ulcer, or long-bone fracture.
• Patients with clinical history of hemoptysis or hematemesis.
• Patients with any history of a bleeding diathesis or coagulopathy.
• Patients with a PEG or G tube cannot be enrolled into this trial.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning bevacizumab.
• Patients with an impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Patients who have any severe and/or uncontrolled medical conditions or other
• conditions that could affect their participation such as:
• severe impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
• uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN.

Where it is running

• Wilshire Oncology Medical Group — LaVerne, California, United States
• Eastern Connecticut Hematology Oncology — Norwich, Connecticut, United States
• Aventura Medical Center — Aventura, Florida, United States
• Florida Cancer Specialists — Fort Myers, Florida, United States
• Mercy Hospital — Portland, Maine, United States
• Center for Cancer and Blood Disorders — Bethesda, Maryland, United States
• National Capital Clinical Research Associates — Bethesda, Maryland, United States
• Oncology Hematology Care — Cincinnati, Ohio, United States
• Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center — Columbus, Ohio, United States
• South Carolina Oncology Associates, PA — Columbia, South Carolina, United States
• Chattanooga Oncology Hematology Associates — Chattanooga, Tennessee, United States
• Tennessee Oncology, PLLC — Nashville, Tennessee, United States
• Texas Oncology — Dallas, Texas, United States
• Fairfax Northern Virginia Hem-Onc — Fairfax, Virginia, United States
• Virginia Cancer Institute — Richmond, Virginia, United States

Full record on ClinicalTrials.gov

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