NCT01300962

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

A Four Part, Phase I Dose-Escalation Study of the Combinations of Concurrent BKM120 and Capecitabine, or Concurrent BYL719 and Capecitabine, or Concurrent BKM120 and Capecitabine and Trastuzumab, or Concurrent BKM120 and Capecitabine and Lapatinib in Patients With Metastatic Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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).

Detailed description

STUDY OBJECTIVES Primary Objectives * To determine the safety, DLT, and MTD of BKM120 when administered concomitantly with capecitabine in patients with metastatic breast cancer (ARM A) * To determine the safety, DLT, and MTD of BYL719 when administered concomitantly with capecitabine in patients with metastatic breast cancer (ARM B) * To determine the safety, DLT, and MTD of BKM120 when administered concomitantly with capecitabine and trastuzumab in patients with metastatic breast cancer (ARM C) * To determine the safety, DLT, and MTD of BKM120 when administered concomitantly with capecitabine and lapatinib in patients with metastatic breast cancer (ARM D) Secondary Objectives * To characterize the safety and tolerability of BKM120 in combination with capecitabine including acute and chronic toxicities * To characterize the safety and tolerability ofBYL719 in combination with capecitabine including acute and chronic toxicities * To characterize the safety and tolerability of BKM120 in combination with capecitabine and trastuzumab, including acute and chronic toxicities * To characterize the safety and tolerability of BKM120 in combination with capecitabine and lapatinib, including acute and chronic toxicities Exploratory Objectives * To obtain primary, archived paraffin-embedded tissues to evaluate intrinsic breast cancer subtype (i.e., HER2, luminal B, etc.) and other important predictive biomarkers (PI3K activating mutations, pAKT, p-mTOR), and explore correlations with therapeutic response to BKM120 or BYL719 in combination with capecitabine, with or without the addition of lapatinib or trastuzumab * To evaluate the PK profile of BKM120 with concomitant capecitabine * To examine other signaling pathway signatures * To examine drug effect in pre- and post-treatment core biopsy specimens (optional) from appropriate patients * To explore patient motivators for enrolling in early phase studies through patient interview Outline: This study is a four-arm multi-center, open-label phase I clinical trial testing the hypothesis that the addition of BKM120 to capecitabine (ARM A); the addition of BYL719 to capecitabine (ARM B); the addition of BKM120 to capecitabine plus trastuzumab (ARM C); or the addition of BKM120 to capecitabine plus lapatinib (ARM D) will be safe and tolerable as evidenced by the DLT seen. Following screening and informed consent, treatment will be initiated with one of the following: ARM A: BKM120 PO daily for 21 days (3 weeks) plus capecitabine PO BID for 2 weeks (no capecitabine is administered during the third week). ARM B: BYL719 PO BID for 21 days (3 weeks) plus capecitabine PO BID for 2 weeks (no capecitabine is administered during the third week of the cycle) ARM C: BKM120 PO daily for 21 days (3 weeks) plus capecitabine PO BID for 2 weeks (no capecitabine is administered during the third week) plus trastuzumab by intravenous infusion on Day 1 ARM D: BKM120 PO daily for 21 days (3 weeks) plus capecitabine PO BID for 2 weeks (no capecitabine is administered during the third week) plus lapatinib PO daily for 21 days. The consents are separate documents and the patient and the study team know ahead of time which Arm is open and enrolling and can therefore focus their discussion with the patient on that ARM. Cycles in each arm will be repeated every 3 weeks (21 days). Patients will continue on protocol-based therapy until progression, unacceptable toxicity, study withdrawal, or patient death.

Conditions

• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	BMK120	BKM120 PO 50, 80 or 100mg every day for each day of each 21 day cycle. Number of cycles: until progression of disease; unacceptable toxicity, withdrawal or death.
DRUG	Capecitabine	875-1250mg/m2 PO BID for two weeks followed by one week rest every three week cycle. Number of cycles: until progression of disease, unacceptable toxicity, withdrawal or death.
DRUG	BYL719	BYL719 200mg PO BID for 21 days (3 weeks) in combination with capecitabine 1000 mg/m2 PO BID for 2 weeks
DRUG	Trastuzumab	trastuzumab infusion on day 1 of each cycle.
DRUG	Lapatinib	lapatinib daily for 21 days in each cycle.

Timeline

• Start date: 2011-08-01
• Primary completion: 2017-02-07
• Completion: 2018-12-31
• First posted: 2011-02-23
• Last updated: 2023-12-04

Locations

2 sites across 1 country: United States