A Study Of Everolimus, Trastuzumab And Vinorelbine In HER2-Positive Breast Cancer Brain Metastases

Completed · Phase 2

Conditions studied: HER-2 Positive Breast Cancer

In brief

Purpose: This study is a single-arm, open-label phase II clinical trial testing the hypothesis that daily everolimus plus weekly vinorelbine and trastuzumab will be effective, safe, and tolerable among patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases. Once enrolled, patients will receive everolimus PO daily in combination with weekly intravenous (IV) vinorelbine and trastuzumab. Cycles will be repeated every 3 weeks (21 days). At the time of progression, patients will come off study. Participants: Up to 35 adults over 21 with HER-2 positive breast cancer that has metastasized to the brain.

Key facts

Study ID

NCT01305941

Run by

UNC Lineberger Comprehensive Cancer Center

People needed

32

Starts

2011-09-01

Expected to finish

2017-10-16

Last updated by the study team

2018-12-17

Who can join

Age: 21 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically-confirmed HER2-positive (IHC 3+ or fluorescence in situ hybridization (FISH) amplified; by clinical assay on either primary or metastatic tumor) adenocarcinoma of the breast with at least one progressive and/or new metastatic brain lesion (>/=5 mm on radiographic imaging) after receipt of intracranial radiation therapy (whole brain radiation therapy, stereotactic radiosurgery, gamma knife, or equivalent). Patients in whom brain metastases (BM) are asymptomatic and detected during routine brain MRI screening per institutional protocols are eligible.
• Prior intracranial radiation therapy (whole brain radiation therapy, stereotactic radiosurgery, gamma knife or equivalent) is allowed but not required.
• Patients with no prior treatment with intracranial Response (ICR) may be included unless ICR is emergently indicated (in consultation with a local therapist, ie neurosurgeon or radiation oncologist)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Life expectancy >12 weeks.
• At least 21 years of age.
• No prior mTOR inhibitors
• Prior navelbine allowed provided navelbine therapy discontinued >/= 12 months from Day 1 of treatment under this protocol.
• Last anti-cancer treatment (including any investigational drug) >/= 2 weeks from initiation of protocol based therapy, provided all adverse events (AEs) (other than alopecia) have resolved to ≤grade 1 at baseline.
• No active serious infection or other comorbid illness which would impair ability to participate in the trial.
• Left ventricular ejection fraction assessment (echocardiogram or multigated acquisition scan (MUGA) scan) performed within 4 weeks prior to study initiation, showing a Left ventricular ejection fraction (LVEF) value ≥ lower limit of normal (LLN).
• If patient is on dexamethasone, must be on stable or decreasing dose of dexamethasone for ≥7 days. If patient is on different glucocorticoid e.g., prednisone, must be converted to dexamethasone prior to enrollment. Refer to dose modification of everolimus for patients taking dexamethasone.
• Interval ≥4 weeks between open brain biopsy and initiation of protocol-based therapy.
• international normalized ratio (INR) ≤2.0. Anticoagulation is allowed if target INR ≤2.0 on a stable dose of warfarin or if patient on a stable dose of Low-molecular-weight (LMW) heparin for >1 weeks at time of enrollment.
• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN. Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Patients must have adequate organ function as evidenced by:
• Absolute neutrophil count ≥1.5/µL
• Platelet count ≥100,000/µL
• Hg ≥9 g/dL
• Bilirubin ≤1.5 x upper limit of normal (ULN)
• aspartate aminotransferase (AST) or Alanine transaminase (ALT) ≤2.5 x ULN (≤5 x ULN if liver metastases are present)
• Serum creatinine ≤1.5 x ULN
• Archived, paraffin-embedded tissue block (primary or metastatic) available for genomic studies is required.
• Signed, institutional review board (IRB)-approved written informed consent.

You may not qualify if…

• Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus); patients who have received prior treatment with navelbine within prior 12 months.
• patients with a known hypersensitivity to everolimus or other rapamycins (e.g. sirolimus, temsirolimus) or to its excipients.
• Patients requiring treatment with any other systemic glucocorticoid. Note: This restriction regarding choice of glucocorticoid does not apply should patient need <2 week course of glucocorticoid for treatment of non-infectious pneumonitis during study (see section 4.5.2).
• Patients with a known hypersensitivity to vinorelbine or to its excipients.
• Prior allergic reaction to trastuzumab for the treatment of metastatic breast cancer.
• Concurrent or planned radiation, hormonal, chemotherapeutic, experimental or targeted biologic therapy.
• Peripheral neuropathy ≥grade 3.
• Evidence of frank hemorrhage or impending herniation on baseline brain imaging. Note: asymptomatic micro-hemorrhage is allowed.
• Evidence of diffuse leptomeningeal disease on brain MRI or by previously documented Cerebrospinal fluid (CSF) cytology. Note: discrete dural metastases are permitted.
• Active cardiac disease including any of the following:
• Angina pectoris that requires the use of anti-anginal medication;
• Ventricular arrhythmias except for benign premature ventricular contractions;
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication;
• Conduction abnormality requiring a pacemaker;
• Valvular disease with documented compromise in cardiac function;
• Symptomatic pericarditis
• History of cardiac dysfunction including any one of the following:
• Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function;
• History of documented congestive heart failure (New York Heart Association functional classification III-IV);
• Documented cardiomyopathy
• Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients that may require major surgery during the course of the study.
• Patients should not receive immunization with attenuated live vaccines within 1 week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guérin (BCG), yellow fever, varicella, and Typhoid Vaccine Live Oral (TY21a) typhoid vaccines.
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• severely impaired lung function, defined as spirometry and diffusion lung capacity for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is ≤88% at rest on room air

Where it is running

• University Of Alabama at Birmingham — Birmingham, Alabama, United States
• UNC Lineberger Comprehensive Cancer Center — Chapel Hill, North Carolina, United States
• Carolinas Healthcare System — Charlotte, North Carolina, United States
• Vanderbilt-Ingram Cancer Center — Nashville, Tennessee, United States

Full record on ClinicalTrials.gov

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