BKM120 and Fulvestrant for Treating Postmenopausal Patients With Estrogen Receptor-Positive Stage IV Breast Cancer

Completed · Phase 1

Conditions studied: Estrogen Receptor-positive Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer

In brief

This phase I trial will determine the Maximum Tolerated Dose (MTD) of BKM120 when given together with fulvestrant in treating postmenopausal patients with estrogen receptor-positive (ER+) stage IV breast cancer. The toxicity profile of this combination therapy will also be described. Inhibition of PI3K by BKM120 may enhance programmed cell death (apoptosis) in estrogen receptor positive (ER+) breast cancer cells. Giving fulvestrant together with BKM 120 may enhance this apoptotic effect, providing a novel therapeutic strategy for patients with metastatic ER+ breast cancer.

Key facts

Study ID

NCT01339442

Run by

Washington University School of Medicine

People needed

31

Starts

2011-11-14

Expected to finish

2016-12-28

Last updated by the study team

2017-01-25

Who can join

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

You may qualify if…

• Patient must be ≥ 18 years of age
• Patient must be a postmenopausal woman, defined by one of the following criteria:
• Women ≥ 60 years
• Women aged 45-59 years with spontaneous cessation of menses ≥ 12 months prior to registration
• Women aged 45-59 years with cessation of menses of duration < 12 months or secondary to hysterectomy AND an follicle-stimulating hormone (FSH) level in the postmenopausal range according to institutional standards (or > 34.4 IU/L if institutional range is not available) prior to registration
• Women aged 45-59 years on hormonal replacement therapy who have discontinued hormonal therapy AND an FSH level in the postmenopausal range according to institutional standards (or > 34.4 IU/L if institutional range is not available) prior to registration
• Status post bilateral surgical oophorectomy
• Patient must have a negative serum pregnancy test within 48 hours before starting study treatment (if a woman of childbearing potential)
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patient must have histologically or cytologically confirmed invasive breast cancer that is stage IV or metastatic (histologic/cytologic confirmation of recurrence preferred, but not required)
• Patient must have a representative tumor tissue specimen available; archival tissue is allowed
• Either the primary or the metastatic tumor must be positive for estrogen receptor (>= 1% tumor cell staining by immunohistochemistry or an Allred Score of >= 3 by immunohistochemistry)
• Patient must have at least one site of measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
• Patient must have had no more than 3 lines of systemic therapy (including endocrine therapy) for metastatic disease to be eligible for phase IB and the last 10 patients of Cohort C; there is no limitation on the numbers of prior systemic therapies for phase IA and the first 2 patients of Cohort C
• Patients who are currently taking fulvestrant without disease progression are eligible
• Patient must have a life expectancy of >= 12 weeks
• Patient must have adequate oran function as defined as:
• Absolute neutrophil count (ANC) >= 1500/uL
• Platelet count >= 100,000/uL
• Hemoglobin >= 9 g/dL
• Serum creatinine =< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3.0 x ULN if liver metastases are present)
• Serum bilirubin =< ULN (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
• Serum amylase =< ULN
• Serum lipase =< ULN

You may not qualify if…

• Patient must not have received prior treatment with a P13K inhibitor
• Patient must not have a known hypersensitivity to BKM120 or to its excipients
• Patient must not have untreated brain metastases; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial if the patient is:
• 4 weeks from therapy completion (including radiation and/or surgery)
• Clinically stable at the time of study entry
• Not receiving corticosteroid therapy
• Patient must not have acute or chronic liver disease, renal disease, or pancreatitis
• Patient must not have any of the following mood disorders as judged by the Investigator or a Psychiatrist
• Medically documented history of or active 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)
• Greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
• Patient must not meet 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 select 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)
• Patient must not have >= grade 2 diarrhea
• Patient must not have active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)
• QTc > 480 msec on screening electrocardiogram (ECG) (using the QTcF formula)
• 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 document compromise in cardiac function
• Symptomatic pericarditis
• Patient must not have a history of cardiac dysfunction including any of the following:
• Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Documented cardiomyopathy

Where it is running

• Washington University School of Medicine — St Louis, Missouri, United States

Full record on ClinicalTrials.gov

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