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A Phase Ib Dose Escalation Study of the Combination of LEE011 With Letrozole and Dose Expansion of LEE011 With Hormonal Therapy for the Treatment of Pre-(With Goserelin) and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT02333370
Recruitment Status : Completed
First Posted : January 7, 2015
Last Update Posted : October 26, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:

The purpose of the Phase Ib is to:

  1. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and anti-tumor activity data in Asian non-Japanese patients
  2. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and activity data in Japanese patients
  3. evaluate the safety and anti-tumor activity of LEE011 at the RP2D established in the dose escalation part in combination with a standard dose of letrozole, fulvestrant or tamoxifen plus goserelin in Japanese patients.

Condition or disease Intervention/treatment Phase
Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer Drug: LEE011 Drug: Letrozole Drug: Tamoxifen Drug: Fulvestrant Drug: goserelin Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Dose Escalation Study of the Combination of LEE011 With Letrozole and Dose Expansion of LEE011 With Hormonal Therapy for the Treatment of Pre-(With Goserelin) and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer
Actual Study Start Date : February 4, 2015
Actual Primary Completion Date : September 30, 2022
Actual Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: LEE011 +Letrozole
LEE011 - 3 weeks on 1 week off Letrozole 2.5mg - Once daily
 Drug: LEE011
LEE011 as 50 mg and 200 mg hard gelatin oral capsules as individual patient supply packaged in bottles. LEE011 will be taken QD - days 1-21 of each 28 days cycle.

Drug: Letrozole
25mg
Experimental: LEE011 + Tamoxifen
LEE011 - 3 weeks on 1 week off Tamoxifen 20mg - Once daily
 Drug: Tamoxifen
20 mg

Drug: goserelin
Experimental: LEE011 + Fulvestrant
LEE011 - 3 weeks on 1 week off Fulvestrant 500 mg - Dosed every 28 days (Day 1 for each cycle) with 1 additional dose on Day 15 of Cycle 1
 Drug: Fulvestrant
500 mg


Outcome Measures
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Primary Outcome Measures :
  1. Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs) [ Time Frame: first cycle (28 days) ]
    DLTs at each dose level associated with administration of LEE011 and letrozole

  2. Phase Ib Dose Expansion: Number of participants with adverse events (AEs) [ Time Frame: 18 months ]

    This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of AEs, lab abnormalities and other safety parameters.

    For LEE011 and letrozole or tamoxifen or fulvestrant


  3. Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs) [ Time Frame: 18 months ]

    This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of SAEs, lab abnormalities and other safety parameters.

    For LEE011 and letrozole or tamoxifen or fulvestrant



Secondary Outcome Measures :
  1. Number of participants with adverse events (AEs) - Phase Ib dose escalation [ Time Frame: 18 months ]

    This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of AEs, lab abnormalities and other safety parameters.

    For LEE011 and letrozole or tamoxifen or fulvestrant


  2. Number of participants with serious adverse events (SAEs) - Phase Ib dose escalation [ Time Frame: 18 months ]

    This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of SAEs, lab abnormalities and other safety parameters.

    For LEE011 and letrozole or tamoxifen or fulvestrant


  3. Overall Response Rate (ORR) - Phase Ib dose expansion [ Time Frame: 18 months ]
    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

  4. Clinical Benefit Rate (CBR) - Phase Ib dose expansion [ Time Frame: 18 months ]
    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

  5. Composite Plasma pharmacokinetics (PK) parameters of LEE011 (and relevant metabolites) and letrozole - Phase Ib [ Time Frame: C1D1, C1D2, C1D8, C1D15, C1D21, C1D22, C2D15, C3D15 ]
    As assessed by PK parameters such as Cmax, Tmax, AUC0-24hours, accumulation ratio and Ctrough for LEE011 (and relevant metabolites) and letrozole, tamoxifen and fulvestrant

  6. Progression Free Survival (PFS) as per RECIST v1.1- phase Ib dose expansion [ Time Frame: 18 months ]
    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

  7. Overall Survival (OS) - Phase Ib dose expansion [ Time Frame: 18 months ]
    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

  8. Disease Control Rate (DCR) - Phase Ib dose expansion [ Time Frame: 18 months ]
    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

  9. Duration of Response (DOR) - Phase Ib dose expansion [ Time Frame: 18 months ]
    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant


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

Inclusion Criteria:

  • Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy (surgery and/or radiotherapy).
  • Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive breast cancer
  • Patient has HER2-negative breast cancer
  • Patient has adequate bone marrow and organ function

Exclusion Criteria:

  • Patient who received any CDK4/6 inhibitor.
  • Patient has a known hypersensitivity to any of the excipients of LEE011 or letrozole
  • Patients with inflammatory breast cancer.
  • Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer
  • Patient is currently using other anti-cancer therapy
  • Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects.
  • Patient who has received radiotherapy ≤ 4 weeks
  • Patient has a concurrent malignancy or malignancy within 3 years
  • Patient has metastases to the central nervous system (CNS).
  • Patient has a known history of HIV infection

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): NCT02333370


Locations
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Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Japan
Novartis Investigative Site
Nagoya-city, Aichi, Japan, 467-8602
Novartis Investigative Site
Sapporo-city, Hokkaido, Japan, 003-0804
Novartis Investigative Site
Yokohama-city, Kanagawa, Japan, 241-8515
Novartis Investigative Site
Osaka-city, Osaka, Japan, 540-0006
Novartis Investigative Site
Suita city, Osaka, Japan, 565 0871
Novartis Investigative Site
Hidaka-city, Saitama, Japan, 350-1298
Novartis Investigative Site
Kitaadachi-gun, Saitama, Japan, 362-0806
Novartis Investigative Site
Sunto Gun, Shizuoka, Japan, 411 8777
Novartis Investigative Site
Bunkyo ku, Tokyo, Japan, 113-8431
Novartis Investigative Site
Bunkyo ku, Tokyo, Japan, 113-8677
Novartis Investigative Site
Koto ku, Tokyo, Japan, 135 8550
Novartis Investigative Site
Shinagawa-ku, Tokyo, Japan, 142-8666
Novartis Investigative Site
Shinjuku-ku, Tokyo, Japan, 160-0023
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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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02333370    
Other Study ID Numbers: CLEE011A2115C
First Posted: January 7, 2015    Key Record Dates
Last Update Posted: October 26, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Advanced breast cancer
Hormone receptor positive
HER2-negative
LEE011,
Letrozole
 Tamoxifen
Fulvestrant
Postmenopausal Asian women
Pre and Postmenopausal Japanese women
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Letrozole
Fulvestrant
Goserelin
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists