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Completed

NCT Number: NCT02088684

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

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Lyon, France

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

LEE011

Drug

LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes

BYL719

Drug

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

Drug

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

Drug

BKM120: supplied as 10 mg or 50 mg capsules. The capsules will be differentiated through different sizes.

Primary outcomes

  1. Incidence of Dose limiting toxicities (DLTs) - Phase lb only

    Time frame: 28 days

    Dose limiting toxicities

  2. Progression free survival (PFS) - Phase ll only

    Time frame: 36 months

    Progression Free Survival per RECIST v 1.1 by local investigator assessment

Secondary outcomes

  1. Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant

    Time frame: 36 months

    Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity

  2. Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant.

    Time frame: 36 months

    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.

  3. Overall Response Rate (ORR)

    Time frame: 36 months

    ORR is defined as the proportion of patients with a best overall response of complete response or partial response.

  4. Duration of Response (DOR)

    Time frame: 36 months

    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.

  5. Progression Free Survival (PFS) (phase l only)

    Time frame: 36 months

    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.

  6. Overall Survival (OS) - Phase II only

    Time frame: 36 months

    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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2018
Study completion
2018
First posted
Mar 17, 2014
Registry last updated
Dec 17, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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