Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase Ib/II Study of LEE011 in Combination With Fulvestrant and BYL719 or BKM120 in the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Recurrent or Advanced Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02088684
• Other study ID #: CLEE011X2108
• Status: Completed
• Phase: Phase 1
• Start date: May 19, 2014
• Est. completion date: April 17, 2018

Study information

• Verified date: April 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to explore the clinical utility of the three investigational agents in HR+, HER2- breast cancer. LEE011 (CDK4/6 inhibitor), BKM120 (PI3K-pan class I-inhibitor) and BYL719 (PI3K-alpha specific class I inhibitor) in combination with fulvestrant.

This is a multi-center, open-label Phase Ib/II study. The Phase Ib portion of the study is a dose escalation to estimate the MTD and/or RP2D for three regimens: LEE011 with fulvestrant; LEE011 and BKM120 with fulvestrant; LEE011and BYL719 with fulvestrant.

The Phase II portion of the study was planned to be a randomized study to assess the anti-tumor activity as well as safety and tolerability of LEE011 with fulvestrant to LEE011 and BKM120 with fulvestrant, and LEE011 and BYL719 with fulvestrant in patients with ER+/HER2- locally advanced or metastatic breast cancer.

Approximately 216 adult women with ER+/HER2- locally advanced or metastatic breast cancer were planned to be enrolled.

Description:

On 31-May-2016 Novartis's made the decision decision to not open the Phase II portion of the study, for business reasons. Sufficient data had already been collected and no additional data for the triplet combinations was needed. As a result, the Phase II portion of the trial was not opened.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: April 17, 2018
• Est. primary completion date: April 17, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Postmenopausal, Hormone receptor positive (HR+), HER2 negative breast cancer

• Unlimited number of lines of endocrine therapy and up to two lines of cytotoxic chemotherapy in the metastatic setting (Phase Ib)

• Unlimited number of lines of endocrine therapy and one line of cytotoxic chemotherapy in the metastatic setting (Phase II)

Exclusion Criteria:

• HER2-overexpression in the patient's tumor tissue

• Inadequate bone marrow function or evidence of end-organ damage

• Severe or uncontrolled medical issues

• Diabetes mellitus

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• LEE011
LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes
• BYL719
BYL719: supplied as tablets of dosage strength of 10 mg, 50 mg or 200 mg. Tablets will be differentiated through different sizes and/or colors.
• fulvestrant
Fulvestrant will be supplied according to local practice and regulation. Fulvestrant is a commercially available product, comes in 500 mg dose and is an injection for intramuscular (i.m.) administration.
• BKM120
BKM120: supplied as 10 mg or 50 mg capsules. The capsules will be differentiated through different sizes.

Locations

Country	Name	City	State
France	Novartis Investigative Site	Lyon Cedex
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Modena	MO
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Madrid
Taiwan	Novartis Investigative Site	Taipei	Taiwan ROC
United Kingdom	Novartis Investigative Site	Leicester
United States	University of Alabama at Birmingham/ Kirklin Clinic Dept Onc	Birmingham	Alabama
United States	Dana Farber Cancer Institute Onc. Dept.	Boston	Massachusetts
United States	Sarah Cannon Research Institute Onc Dept	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  France,  Italy,  Korea, Republic of,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose limiting toxicities (DLTs) - Phase lb only	Dose limiting toxicities	28 days
Primary	Progression free survival (PFS) - Phase ll only	Progression Free Survival per RECIST v 1.1 by local investigator assessment	36 months
Secondary	Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant	Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity	36 months
Secondary	Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant.	To characterize the PK profiles of LEE011, BKM120, BYL719, and fulvestrant when used in combination as well as to evaluate any other clinically significant metabolites that may be identified. PK parameters for LEE011, BKM120 and BYL719, including but not limited to Cmax, Cmin, Tmax, AUCtau, accumulation ratio (Racc),and Ctrough values for fulvestrant.	36 months
Secondary	Overall Response Rate (ORR)	ORR is defined as the proportion of patients with a best overall response of complete response or partial response.	36 months
Secondary	Duration of Response (DOR)	Duration of Response is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer.	36 months
Secondary	Progression Free Survival (PFS) (phase l only)	PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.	36 months
Secondary	Overall Survival (OS) - Phase II only	OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive.	36 months

External Links

•   link to Novartis Clinical Trial result Database