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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
199

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 14, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 13, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 13, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 23, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 6, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 12, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 1, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings