Clinical trial NCT02333370: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer
Keywords: Advanced breast cancer
Hormone receptor positive
HER2-negative
LEE011,
Letrozole
Tamoxifen
Fulvestrant
Postmenopausal Asian women
Pre and Postmenopausal Japanese women
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-01-07
Enrollment: 88
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs)
timeFrame: first cycle (28 days)
measure: Phase Ib Dose Expansion: Number of participants with adverse events (AEs)
timeFrame: 18 months
measure: Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs)
timeFrame: 18 months
Secondary outcomes:
measure: Number of participants with adverse events (AEs) - Phase Ib dose escalation
timeFrame: 18 months
measure: Number of participants with serious adverse events (SAEs) - Phase Ib dose escalation
timeFrame: 18 months
measure: Overall Response Rate (ORR) - Phase Ib dose expansion
timeFrame: 18 months
measure: Clinical Benefit Rate (CBR) - Phase Ib dose expansion
timeFrame: 18 months
measure: Composite Plasma pharmacokinetics (PK) parameters of LEE011 (and relevant metabolites) and letrozole - Phase Ib
timeFrame: C1D1, C1D2, C1D8, C1D15, C1D21, C1D22, C2D15, C3D15
measure: Progression Free Survival (PFS) as per RECIST v1.1- phase Ib dose expansion
timeFrame: 18 months
measure: Overall Survival (OS) - Phase Ib dose expansion
timeFrame: 18 months
measure: Disease Control Rate (DCR) - Phase Ib dose expansion
timeFrame: 18 months
measure: Duration of Response (DOR) - Phase Ib dose expansion
timeFrame: 18 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Hidaka-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Kitaadachi-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Sunto Gun
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Yap YS, Chiu J, Ito Y, Ishikawa T, Aruga T, Kim SJ, Toyama T, Saeki T, Saito M, Gounaris I, Su F, Ji Y, Han Y, Gazdoiu M, Masuda N. Ribociclib, a CDK 4/6 inhibitor, plus endocrine therapy in Asian women with advanced breast cancer. Cancer Sci. 2020 Sep;111(9):3313-3326. doi: 10.1111/cas.14554. Epub 2020 Jul 28.