Study of BKM120 or BYL719 and Capecitabine in Patients With Metastatic Breast Cancer

Completed · Phase 1

Conditions studied: Metastatic Breast Cancer

In brief

This phase I study has been designed to establish the safety, tolerability and maximum tolerated dose (MTD) of four separate regimens for patients with metastatic breast cancer: dose- escalating BKM120 when combined with capecitabine (Arm A), with capecitabine and trastuzumab (Arm C), or with capecitabine and lapatinib (Arm D) and dose- escalating BEZ235 when combined with capecitabine (Arm B).

Key facts

Study ID

NCT01300962

Run by

UNC Lineberger Comprehensive Cancer Center

People needed

47

Starts

2011-08-01

Expected to finish

2018-12-31

Last updated by the study team

2023-12-04

Who can join

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

You may not qualify if…

• Subjects meeting any of the exclusion criteria listed below at baseline will be excluded from study participation:
• Receiving concurrent endocrine, cytotoxic, or biologic agent(s) or within time limits specified above prior to study day 1
• Receiving any other investigational agents currently, or within time limits specified above prior to study day 1
• Received wide field radiotherapy ≤4 weeks, or SRS or gamma knife for brain metastasis ≤ 2 weeks or limited field radiation for palliation ≤2 weeks prior to starting either BYL719 or BKM120 or have not recovered from side effects of such therapy
• Have undergone major surgery ≤2 weeks prior to starting BKM120 or BYL719 or have not recovered from side effects of such therapy
• Prior treatment with treatment doses of capecitabine (prior radio-sensitizing doses of capecitabine are allowed as long as the patient did not progress on capecitabine)
• Prior treatment with a PI3K inhibitor
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
• Currently receiving treatment with medication known to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
• Patients currently receiving chronic systemic treatment with steroids or another immunosuppressive agent; 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, or if ARM C patient with brain metastases treated with glucocorticoid is enrolled. Topical applications (e.g., rash), inhaled sprays, eye drops or local injections of steroids are allowed.
• Known coagulopathies, and those who require therapeutic anticoagulation with coumarin-derivative anticoagulants
• Presence of acute or chronic liver, renal disease, or pancreatitis
• For all Arms, patients with poorly controlled diabetes mellitus, and/or with clinical signs, and/or steroid-induced diabetes mellitus; for Arm B, patients requiring insulin treatment
• History of gestational diabetes mellitus
• Known diagnosis of human immunodeficiency virus (HIV) infection
• For Arms A, C or D, patients with the following mood disorders as judged by the investigator or a psychiatrist, or as result of patient's mood assessment questionnaire:
• Medically documented history of major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) or patients with active severe personality disorders (defined according to DSM-IV). NOTE: for patients with psychotropic treatments ongoing at baseline, the dose and schedule should not be modified within the previous 6 weeks prior to D1 of treatment with BKM120
• ≥ CTCAE grade 3 anxiety
• At screening, meets the cut-off score of ≥10 in the Patient Health Questionnaire (PHQ-9) or a cut-off of ≥ 15 in the Generalized Anxiety Disorder (GAD-7) mood scale, respectively, or selects a positive response of 1, 2 or 3 to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study unless overruled by the psychiatric assessment
• Note: The psychiatric judgment overrules the mood assessment questionnaire result/investigator's judgment.
• Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication and during the entire study due to potential CYP3A4 interaction with the study medication. Orange juice is allowed
• Intake of any herbal preparations or medications (e.g., including, but not limited to, Saint-Johns Wort and ginkgo biloba) and dietary supplements within 7 days prior to first dose of study drug
• For ARMS A, C and D, unable or unwilling to discontinue use of any drug known to be a strong or moderate inhibitor or inducer of CYP3A4 (prohibited inducers and inhibitors must be discontinued within 2 weeks prior to first dose of study drug) (see Appendix B); please note that co-treatment with weak inhibitors of CYP3A4 is allowed.
• Patients who received live vaccines or who have close contact with people who have received live vaccines within 7 days of day 1 of study treatment (see Appendix B)

Where it is running

• Lineberger Comprehensive Cancer Center — Chapel Hill, North Carolina, United States
• Duke Comprehensive Cancer Center — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

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