NCT01339442

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

A Phase 1 Trial of BKM 120, a Novel Oral Selective Phosphatidylinositol-3-kinase (PI3K) Inhibitor, in Combination With Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive Metastatic Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of BKM120 (PI3K inhibitor BKM120) in combination with fulvestrant. II. To evaluate the toxicity profile of BKM120 in combination with fulvestrant. SECONDARY OBJECTIVES: I. To evaluate the toxicity profile of BKM120 in combination with fulvestrant when administered for at least 3 months. II. To determine the steady state blood concentrations of BKM120 when combined with fulvestrant. III. To evaluate the anti-tumor effect (partial response \[PR\], complete response \[CR\], stable disease \[SD\], and progressive disease \[PD\]) of BKM120 in combination with fulvestrant in patients with ER+ metastatic breast cancer. TERTIARY OBJECTIVES: I. To examine baseline tumor specimens for phosphatidylinositol 3-kinase (PI3K) pathway abnormalities, and to correlate with treatment response. II. To examine the PIK3 catalytic alpha polypeptide (PIK3CA) mutation status in circulating deoxyribonucleic acid (DNA) at baseline and following study therapy and to correlate with tumor tissue PIK3CA status and treatment response. III. To determine effects of study therapy on fasting C-peptide and glucose. IV. To evaluate target inhibition by BKM120 on serial tumor biopsies collected before and following study therapy. V. To evaluate the effect of BKM120 in combination with fulvestrant on tumor cell proliferation and apoptosis. VI. To obtain preliminary pilot data to evaluate the effect of BKM120 on tumor cell proliferation, as measured by FLT-PET/CT (Phase IB) OUTLINE: This is a dose-escalation study of PI3K inhibitor BKM120. Patients receive PI3K inhibitor BKM120 orally (PO) once daily (QD) on days 1-28 (if enrolled in Phase IA or Cohort C) or on a 5 days on/2 days off schedule (if enrolled in Phase IB). All patients will receive fulvestrant intramuscularly (IM) on days 1 and 15 of Cycle 1 and day 1 of all subsequent cycles. Cycles repeat ever 28 days in the absence of disease progression or unacceptable toxicity. Two OPTIONAL FLT-PET/CT scans: the first one done at baseline before the start of BKM120 and the second one done between Day 16 and Day18 after BKM120 is started. After completion of study treatment, patients are followed up for 28 days.

Conditions

• Estrogen Receptor-positive Breast Cancer
• Recurrent Breast Cancer
• Stage IV Breast Cancer

Interventions

Type	Name	Description
DRUG	BKM120
DRUG	Fulvestrant
PROCEDURE	biopsy	Correlative studies

Timeline

• Start date: 2011-11-14
• Primary completion: 2016-12-21
• Completion: 2016-12-28
• First posted: 2011-04-20
• Last updated: 2017-01-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study