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

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ClinicalTrials.gov Identifier: NCT02734615
Recruitment Status : Active, not recruiting
First Posted : April 12, 2016
Last Update Posted : April 13, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic ER+ Breast Cancer Drug: LSZ102 Drug: LEE011 Drug: BYL719 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 199 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 14, 2016
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Ribociclib

Arms and Interventions
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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 Name: ribociclib, Kisqali
Experimental: Arm C
Patients will get LSZ102 in combination with BYL719 during dose escalation.
 Drug: LSZ102
LSZ102

Drug: BYL719
BYL719
Other Name: 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 Name: ribociclib, Kisqali
Experimental: Arm 3
Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion
 Drug: LSZ102
LSZ102

Drug: LEE011
LEE011
Other Name: ribociclib, Kisqali
Experimental: Arm 4
Patient will get LSZ102 in combination with BYL719 during dose expansion
 Drug: LSZ102
LSZ102

Drug: BYL719
BYL719
Other Name: alpelisib


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. Duration of Response (DOR) [ Time Frame: 3 years ]
    Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719

  3. Progression Free Survival (PFS) [ Time Frame: 3 years ]
    Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719

  4. Disease control rate (DCR) [ Time Frame: 3 years ]
    Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719

  5. Plasma concentration of study medications [ Time Frame: 1 cycle (28 day cycle) ]
    Plasma concentration versus time

  6. 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

  7. Levels of Pharmacodynamic marker Estrogen receptor (ER) [ Time Frame: 3 years ]
    To assess pharmacodynamics effect

  8. Levels of Pharmacodynamic marker Progesterone receptor (PgR) [ Time Frame: 3 years ]
    To assess the pharmacodynamic effect

  9. Levels of Pharmacodynamic marker pS6 [ Time Frame: 3 years ]
    To assess the pharmacodynamic effect

  10. Pharmacokinetics (PK) parameter AUC [ Time Frame: 6 cycles (28 day cycle) ]
    AUC = Area under curve

  11. PK parameter Cmax [ Time Frame: 6 cycles (28 day cycle) ]
    Cmax = Maximum observed plasma concentration after drug administration

  12. PK parameter Tmax [ Time Frame: 6 cycles (28 day cycle) ]
    Tmax = Time to reach Cmax

  13. PK parameter Cmin [ Time Frame: 6 cycles (28 day cycle) ]
    Cmin = Minimum observed plasma concentration after drug administration


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02734615


Locations
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United States, Massachusetts
Massachusetts General Hospital Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center SC - LSZ102X2101
Houston, Texas, United States, 77030
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1200
France
Novartis Investigative Site
Lyon Cedex, France, 69373
Germany
Novartis Investigative Site
Ulm, Germany, 89081
Italy
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Milano, MI, Italy, 20141
Japan
Novartis Investigative Site
Koto ku, Tokyo, Japan, 135 8550
Singapore
Novartis Investigative Site
Singapore, Singapore, 169610
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02734615    
Other Study ID Numbers: CLSZ102X2101
2015-004016-38 ( EudraCT Number )
First Posted: April 12, 2016    Key Record Dates
Last Update Posted: April 13, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
LSZ102
LEE011
ribociclib
Kisqali
BYL719
alpelisib
ER+ breast cancer
advanced ER+ breast cancer
metastatic ER+ breast cancer
SERD
 SERM
fulvestrant
tamoxifen
aromatase inhibitor
ESR1
mtESR1
wtESR1
estrogen receptor
endocrine therapy
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases