Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers

July 28, 2022 updated by: Novartis Pharmaceuticals

A Phase I/Ib, Open Label Study of LSZ102 Single Agent and LSZ102 in Combination With Either LEE011 (LSZ102 + LEE011) or BYL719 (LSZ102 + BYL719) in Patients With Advanced or Metastatic ER+ Breast Cancer Who Have Progressed After Endocrine Therapy

To characterize the safety and tolerability, identify recommended doses and regimens for future studies, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LSZ102 as a single agent and in combination with either LEE011 or BYL719 in adult patients with locally advanced or metastatic ER+ breast cancer who have progressed after endocrine therapy.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

199

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Bruxelles, Belgium, 1200
        • Novartis Investigative Site
  • France
      • Lyon Cedex, France, 69373
        • Novartis Investigative Site
  • Germany
      • Ulm, Germany, 89081
        • Novartis Investigative Site
  • Italy
    • MI
      • Milano, MI, Italy, 20133
        • Novartis Investigative Site
      • Milano, MI, Italy, 20141
        • Novartis Investigative Site
  • Japan
    • Tokyo
      • Koto ku, Tokyo, Japan, 135 8550
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 169610
        • Novartis Investigative Site
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Massachusetts General Hospital
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center SC - LSZ102X2101

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Written informed consent must be obtained prior to any procedures
  • Histologically and/or cytologically confirmed diagnosis of ER+/HER2- breast cancer
  • Advanced or metastatic breast cancer
  • Must be able to swallow tablets and capsules

Exclusion Criteria:

  • Symptomatic CNS metastases
  • Patients whose laboratory values do not meet protocol criteria
  • Clinically significant cardiac disease
  • Impaired gastrointestinal function (GI) or GI disease that may significantly alter the absorption of oral medications

Other protocol defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm A
Patients will get LSZ102 single agent during dose escalation.
Drug: LSZ102
LSZ102
EXPERIMENTAL: Arm B
Patients will get LSZ102 in combination with LEE011 during dose escalation.
Drug: LSZ102
LSZ102
Drug: LEE011
LEE011
Other Names:
  • ribociclib, Kisqali
EXPERIMENTAL: Arm C
Patients will get LSZ102 in combination with BYL719 during dose escalation.
Drug: LSZ102
LSZ102
Drug: BYL719
BYL719
Other Names:
  • alpelisib
EXPERIMENTAL: Arm 1
Patients will get LSZ102 single agent during dose expansion
Drug: LSZ102
LSZ102
EXPERIMENTAL: Arm 2
Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion
Drug: LSZ102
LSZ102
Drug: LEE011
LEE011
Other Names:
  • ribociclib, Kisqali
EXPERIMENTAL: Arm 3
Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion
Drug: LSZ102
LSZ102
Drug: LEE011
LEE011
Other Names:
  • ribociclib, Kisqali
EXPERIMENTAL: Arm 4
Patient will get LSZ102 in combination with BYL719 during dose expansion
Drug: LSZ102
LSZ102
Drug: BYL719
BYL719
Other Names:
  • alpelisib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose limiting toxicities (DLTs)
Time Frame: Day 1 - Day 28 of Cycle 1 (28 day cycle)
The dose escalation part of the study will be guided by well-established statistical methods/models to estimate the maximum tolerated doses (MTD)and/or recommended doses for expansion (RDE). Safety, pharmacokinetic and pharmacodynamics data will guide dose escalation decisions.
Day 1 - Day 28 of Cycle 1 (28 day cycle)
Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
Time Frame: Approximately 3 years
Incidence and severity of adverse events, serious adverse events, clinical laboratory values, vital signs, ECGs, dose interruptions, dose reductions and dose intensity.
Approximately 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: Approximately 3 years
Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719. ORR is defined as the proportion of patients with a best overall response of complete response or partial response.
Approximately 3 years
Duration of Response (DOR)
Time Frame: 3 years
Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
3 years
Progression Free Survival (PFS)
Time Frame: 3 years
Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
3 years
Disease control rate (DCR)
Time Frame: 3 years
Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719
3 years
Plasma concentration of study medications
Time Frame: 1 cycle (28 day cycle)
Plasma concentration versus time
1 cycle (28 day cycle)
Plasma concentration under fasted condition and fed condition
Time Frame: Up to 2 cycles (28 day cycle)
Plasma concentration versus time under fasted and fed conditions
Up to 2 cycles (28 day cycle)
Levels of Pharmacodynamic marker Estrogen receptor (ER)
Time Frame: 3 years
To assess pharmacodynamics effect
3 years
Levels of Pharmacodynamic marker Progesterone receptor (PgR)
Time Frame: 3 years
To assess the pharmacodynamic effect
3 years
Levels of Pharmacodynamic marker pS6
Time Frame: 3 years
To assess the pharmacodynamic effect
3 years
Pharmacokinetics (PK) parameter AUC
Time Frame: 6 cycles (28 day cycle)
AUC = Area under curve
6 cycles (28 day cycle)
PK parameter Cmax
Time Frame: 6 cycles (28 day cycle)
Cmax = Maximum observed plasma concentration after drug administration
6 cycles (28 day cycle)
PK parameter Tmax
Time Frame: 6 cycles (28 day cycle)
Tmax = Time to reach Cmax
6 cycles (28 day cycle)
PK parameter Cmin
Time Frame: 6 cycles (28 day cycle)
Cmin = Minimum observed plasma concentration after drug administration
6 cycles (28 day cycle)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 14, 2016

Primary Completion (ACTUAL)

September 13, 2021

Study Completion (ACTUAL)

September 13, 2021

Study Registration Dates

First Submitted

March 23, 2016

First Submitted That Met QC Criteria

April 6, 2016

First Posted (ESTIMATE)

April 12, 2016

Study Record Updates

Last Update Posted (ACTUAL)

August 1, 2022

Last Update Submitted That Met QC Criteria

July 28, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLSZ102X2101
  • 2015-004016-38 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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