Clinical Trials /

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

NCT02088684

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer
  • 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 IDs

  • ORG STUDY ID: CLEE011X2108
  • NCT ID: NCT02088684

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
LEE011LEE011 + BKM120 + fulvestrant
BYL719LEE011 + BYL719 + fulvestrant
fulvestrantLEE011 + BKM120 + fulvestrant
BKM120LEE011 + BKM120 + fulvestrant

Purpose

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 will 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 will be enrolled.

Trial Arms

NameTypeDescriptionInterventions
LEE011 + BKM120 + fulvestrantExperimentalLEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
  • LEE011
  • fulvestrant
  • BKM120
LEE011 + BYL719 + fulvestrantExperimentalLEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
  • LEE011
  • BYL719
  • fulvestrant
LEE011 + fulvestrantExperimentalLEE011 - 28 day cycles (3 weeks on, 1 week off) or (continuous daily dosing - dose escalating) fulvestrant - 500 mg i.m. given on Day 1 and Day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
  • LEE011
  • fulvestrant

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose limiting toxicities (DLTs) - Phase lb only
Time Frame:28 days
Safety Issue:
Description:Dose limiting toxicities

Secondary Outcome Measures

Measure:Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant
Time Frame:36 months
Safety Issue:
Description:Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity
Measure:Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant.
Time Frame:36 months
Safety Issue:
Description: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.
Measure:Overall Response Rate (ORR)
Time Frame:36 months
Safety Issue:
Description:ORR is defined as the proportion of patients with a best overall response of complete response or partial response.
Measure:Duration of Response (DOR)
Time Frame:36 months
Safety Issue:
Description: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.
Measure:Progression Free Survival (PFS) (phase l only)
Time Frame:36 months
Safety Issue:
Description: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.
Measure:Overall Survival (OS) - Phase II only
Time Frame:36 months
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Hormone receptor positive, HER2 negative

Last Updated

July 24, 2017