A Phase Ib Dose Escalation Study of the Combination of LEE011 With Letrozole and Dose Expansion of LEE011 With Hormonal Therapy for the Treatment of Pre-(With Goserelin) and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

Novartis Pharmaceuticals88 enrolled

Overview

The purpose of the Phase Ib is to: 1. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and anti-tumor activity data in Asian non-Japanese patients 2. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and activity data in Japanese patients 3. evaluate the safety and anti-tumor activity of LEE011 at the RP2D established in the dose escalation part in combination with a standard dose of letrozole, fulvestrant or tamoxifen plus goserelin in Japanese patients.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

Interventions

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy (surgery and/or radiotherapy). * Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive breast cancer * Patient has HER2-negative breast cancer * Patient has adequate bone marrow and organ function Exclusion Criteria: * Patient who received any CDK4/6 inhibitor. * Patient has a known hypersensitivity to any of the excipients of LEE011 or letrozole * Patients with inflammatory breast cancer. * Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer * Patient is currently using other anti-cancer therapy * Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects. * Patient who has received radiotherapy ≤ 4 weeks * Patient has a concurrent malignancy or malignancy within 3 years * Patient has metastases to the central nervous system (CNS). * Patient has a known history of HIV infection Other protocol-defined inclusion/exclusion criteria may apply

Locations (15)

Novartis Investigative Site

Hong Kong, Hong Kong

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Sapporo, Hokkaido, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Osaka, Osaka, Japan

Novartis Investigative Site

Suita, Osaka, Japan

Novartis Investigative Site

Hidaka, Saitama, Japan

Novartis Investigative Site

Kitaadachi-gun, Saitama, Japan

Novartis Investigative Site

Sunto Gun, Shizuoka, Japan

Novartis Investigative Site

Bunkyo Ku, Tokyo, Japan

...and 5 more locations

Outcomes

Primary Outcomes

Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs)

DLTs at each dose level associated with administration of LEE011 and letrozole

Time frame: first cycle (28 days)

Phase Ib Dose Expansion: Number of participants with adverse events (AEs)

This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of AEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant

Time frame: 18 months

Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs)

This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of SAEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant

Time frame: 18 months

Secondary Outcomes

Number of participants with adverse events (AEs) - Phase Ib dose escalation

Time frame: 18 months

Number of participants with serious adverse events (SAEs) - Phase Ib dose escalation

Time frame: 18 months

Overall Response Rate (ORR) - Phase Ib dose expansion