Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Capecitabine

Trastuzumab

Lapatinib

Antimetabolites

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

BKM 120 plus capecitabine plus trastuzumab

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.

BMK120

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.

BYL719 200mg PO BID for 21 days (3 weeks) in combination with capecitabine 1000 mg/m2 PO BID for 2 weeks

BYL719

trastuzumab infusion on day 1 of each cycle.

lapatinib daily for 21 days in each cycle.

Claire Dees

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).

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.

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

Maximum Tolerated Dose (MTD) will be the highest does at which less than or equal to 1 out of 6 patients have experienced a dose limiting toxicity (DLT)

Dose-limiting toxicities (DLT) will be defined per NCI Common Terminology Criteria for Adverse Events version 4 (CTCAE v4)

Objective response is measured by assessing the tumor response using Recist 1.1 criteria

The best overall response is defined as the best response achieved across all time points prior to progression (for example, a patient who has SD at first assessment, PR at second assessment, and PD on last assessment has a best overall response of PR).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of BKM120 or BYL719 and Capecitabine in Patients With Metastatic Breast Cancer	NCT01300962	Metastatic Brea...	BMK120 Capecitabine BYL719 Trastuzumab Lapatinib	18 Years -	UNC Lineberger Comprehensive Cancer Center
Study of BKM120 or BYL719 and Capecitabine in Patients With Metastatic Breast Cancer	NCT01300962	Metastatic Brea...	BMK120 Capecitabine BYL719 Trastuzumab Lapatinib	18 Years -	UNC Lineberger Comprehensive Cancer Center

Spots Global Cancer Trial Database for bmk120

Every month we try and update this database with for bmk120 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bmk120

Every month we try and update this database with for bmk120 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bmk120 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.