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

Metastatic Breast Cancer Clinical Trial

Official title: 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

Clinical Trial 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).

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

• NCT number: NCT01300962
• Study type: Interventional
• Source: UNC Lineberger Comprehensive Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: August 2011
• Completion date: December 31, 2018