Clinical Trial - NCT02734615

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

Recruiting

Sponsor: Novartis Pharmaceuticals

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02734615

Protocol Info

Short Description: Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers
Long Description: 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
MGH Status: Open
Sponsor: Novartis
Disease Program: Breast

Next Steps


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Purpose

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 Title Intervention Phase
Advanced or Metastatic ER+ Breast Cancer LSZ102 LEE011 BYL719 Phase 1
Study Type Interventional
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

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs) [Time Frame: Day 1 - Day 28 of Cycle 1 (28 day cycle)] [Designated as safety issue: ]

Safety and tolerability of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719 [Time Frame: Approximately 3 years] [Designated as safety issue: ]


Secondary Outcome Measures

Overall response rate (ORR) [Time Frame: Approximately 3 years] [Designated as safety issue: ]

Duration of Response (DOR) [Time Frame: 3 years] [Designated as safety issue: ]

Progression Free Survival (PFS) [Time Frame: 3 years] [Designated as safety issue: ]

Disease control rate (DCR) [Time Frame: 3 years] [Designated as safety issue: ]

Plasma concentration of study medications [Time Frame: 1 cycle (28 day cycle)] [Designated as safety issue: ]

Plasma concentration under fasted condition and fed condition [Time Frame: Up to 2 cycles (28 day cycle)] [Designated as safety issue: ]

Levels of Pharmacodynamic marker Estrogen receptor (ER) [Time Frame: 3 years] [Designated as safety issue: ]

Levels of Pharmacodynamic marker Progesterone receptor (PgR) [Time Frame: 3 years] [Designated as safety issue: ]

Levels of Pharmacodynamic marker pS6 [Time Frame: 3 years] [Designated as safety issue: ]

Pharmacokinetics (PK) parameter AUC [Time Frame: 6 cycles (28 day cycle)] [Designated as safety issue: ]

PK parameter Cmax [Time Frame: 6 cycles (28 day cycle)] [Designated as safety issue: ]

PK parameter Tmax [Time Frame: 6 cycles (28 day cycle)] [Designated as safety issue: ]

PK parameter Cmin [Time Frame: 6 cycles (28 day cycle)] [Designated as safety issue: ]

Estimated Enrollment: 420
Study Start Date: June 2016
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2020
Arms Assigned Interventions

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:LEE011
LEE011

Experimental:Arm C

Patients will get LSZ102 in combination with BYL719 during dose escalation.
Drug:BYL719
BYL719

Experimental:Arm 1

Patients will get LSZ102 single agent during dose expansion

Experimental:Arm 2

Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion

Experimental:Arm 3

Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion

Experimental:Arm 4

Patient will get LSZ102 in combination with BYL719 during dose expansion

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT02734615

Locations

  • United States, Maryland
    • Novartis Investigative Site Baltimore, Maryland, United States, 21287
  • United States, Massachusetts
    • Massachusetts General Hospital Massachusetts General Hospital Boston, Massachusetts, United States, 02114
  • United States, New York
    • Novartis Investigative Site New York, New York, United States, 10065
  • United States, Texas
    • Novartis Investigative Site Houston, Texas, United States, 77030
  • Belgium,
    • Novartis Investigative Site Bruxelles, , Belgium, 1200
  • Canada, Ontario
    • Novartis Investigative Site Toronto, Ontario, Canada, M5G 2M9
  • France,
    • Novartis Investigative Site Lyon Cedex, , France, 69373
  • Germany,
    • Novartis Investigative Site Frankfurt, , Germany, 60590
    • Novartis Investigative Site Heidelberg, , Germany, 69120
    • Novartis Investigative Site Ulm, , Germany, 89081
  • Italy, MI
    • Novartis Investigative Site Milano, MI, Italy, 20133
    • Novartis Investigative Site Milano, MI, Italy, 20141
  • Japan, Tokyo
    • Novartis Investigative Site Koto ku, Tokyo, Japan, 135 8550
  • Singapore,
    • Novartis Investigative Site Singapore, , Singapore, 169610
  • Spain, Catalunya
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08036
  • Spain,
    • Novartis Investigative Site Madrid, , Spain, 28009

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02734615
Other Study ID Numbers: 2015-004016-38
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Novartis:

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:

Breast Neoplasms

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019