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About
This is a phase 1b/2 study to evaluate the safety and clinical activity of the combination of lapatinib, everolimus and capecitabine for the treatment of participants with HER2+ breast cancer with metastases in the brain who have progressed on trastuzumab.
The combination of 2 drugs able to reach the brain (lapatinib and everolimus) that target different parts of the HER2 signaling pathway plus chemotherapy (capecitabine) that has proven benefits in metastatic breast cancer may lead to improved clinical outcomes for participants with CNS metastasis.
Participants will undergo brain MRIs and CT scans of the chest and abdomen to evaluate response to the treatment, regular laboratory tests and echocardiogram or Multi Gated Acquisition Scan (MUGA) to assess cardiac activity
Full description
PRIMARY OBJECTIVES:
I. Central nervous system (CNS) objective response rate at 12 weeks: defined as either a complete response or partial response provided there is no progression of extra-CNS disease, increasing steroid requirements, or worsening of neurologic signs and symptoms (NSS)^34 Lesions will be measured using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
SECONDARY OBJECTIVES:
I. Safety and tolerability. II. Median progression free survival. III. Median overall survival. IV. CNS objective response rate and clinical benefit rate (complete response, partial response and stable disease lasting at least 6 months).
V. Extra-CNS objective response rate according to RECIST1.1.
OUTLINE:
Patients receive lapatinib ditosylate orally (PO) once daily (QD) and everolimus PO QD on days 1-21, and capecitabine PO twice daily (BID) on days 1-14. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment or treatment discontinuation, patients will complete 2 follow up visits within 7 days and at 30 days and then will be followed for survival every 3 months for up to 12 months.
Enrollment
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Inclusion criteria
Exclusion criteria
Patients who have never received trastuzumab
Prior treatment with an mammalian target of rapamycin (MTOR) inhibitor (including everolimus, sirolimus, temsirolimus)
Leptomeningeal carcinomatosis as only site of CNS disease
Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
Patients with clinically significant interstitial lung disease or history of cardiac disease
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
Prior treatment with any investigational drug within the preceding 4 weeks prior to starting study drug
Patients receiving chronic, systemic treatment with corticosteroids (more than 20 mg/day prednisone equivalent, see inclusion criteria) or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
Patients should not receive immunization with attenuated live vaccines within one week of starting study drug 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 (TY)21a 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:
A known history of human immunodeficiency virus (HIV) seropositivity
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus/lapatinib (lapatinib ditosylate) (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
Patients with an active, bleeding diathesis
Patients on warfarin (patients on injectable blood thinners, such as Lovenox, are able to continue those)
Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes; (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of study drug)
Male patient whose sexual partner(s) are women of childbearing potential (WOCBP) who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
Patients with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients
History of noncompliance to medical regimens
Patients unwilling to or unable to comply with the protocol
Primary purpose
Allocation
Interventional model
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9 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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