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

NCT02333370 | Completed Phase 1

• 1 other identifier: CLEE011A2115C
• Study Type: interventional
• Target: 88
• Locations: 3 countries
• Sites: 15

Brief Summary

The purpose of the Phase Ib is to:

1. 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. 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. 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.

Conditions

Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

Keywords

Advanced breast cancer; Hormone receptor positive; HER2-negative; LEE011,; Letrozole; Tamoxifen; Fulvestrant; Postmenopausal Asian women; Pre and Postmenopausal Japanese women

Outcome Measures

Primary Outcomes (3)

• Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs)

  DLTs at each dose level associated with administration of LEE011 and letrozole

  first cycle (28 days)

• Phase Ib Dose Expansion: Number of participants with adverse events (AEs)

  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

  18 months

• Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs)

  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

  18 months

Secondary Outcomes (9)

• Number of participants with adverse events (AEs) - Phase Ib dose escalation

  18 months

• Number of participants with serious adverse events (SAEs) - Phase Ib dose escalation

  18 months

• Overall Response Rate (ORR) - Phase Ib dose expansion

  18 months

• Clinical Benefit Rate (CBR) - Phase Ib dose expansion

  18 months

• Composite Plasma pharmacokinetics (PK) parameters of LEE011 (and relevant metabolites) and letrozole - Phase Ib

  C1D1, C1D2, C1D8, C1D15, C1D21, C1D22, C2D15, C3D15

Study Arms (3)

LEE011 +Letrozole

EXPERIMENTAL

LEE011 - 3 weeks on 1 week off Letrozole 2.5mg - Once daily

Drug: LEE011; Drug: Letrozole

LEE011 + Tamoxifen

EXPERIMENTAL

LEE011 - 3 weeks on 1 week off Tamoxifen 20mg - Once daily

Drug: Tamoxifen; Drug: goserelin

LEE011 + Fulvestrant

EXPERIMENTAL

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

Interventions

LEE011 DRUG

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.

LEE011 +Letrozole

Letrozole DRUG

25mg

LEE011 +Letrozole

Tamoxifen DRUG

20 mg

LEE011 + Tamoxifen

Fulvestrant DRUG

500 mg

LEE011 + Fulvestrant

goserelin DRUG

LEE011 + Tamoxifen

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 467-8602, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 003-0804, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 241-8515, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 540-0006, Japan

Location

Novartis Investigative Site

Suita, Osaka, 565 0871, Japan

Location

Novartis Investigative Site

Hidaka, Saitama, 350-1298, Japan

Location

Novartis Investigative Site

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

Novartis Investigative Site

Sunto Gun, Shizuoka, 411 8777, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 113-8431, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 113-8677, Japan

Location

Novartis Investigative Site

Koto Ku, Tokyo, 135 8550, Japan

Location

Novartis Investigative Site

Shinagawa-ku, Tokyo, 142-8666, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 160-0023, Japan

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Related Publications (2)

• Chiu J, Su F, Joshi M, Masuda N, Ishikawa T, Aruga T, Zarate JP, Babbar N, Balbin OA, Yap YS. Potential value of ctDNA monitoring in metastatic HR + /HER2 - breast cancer: longitudinal ctDNA analysis in the phase Ib MONALEESASIA trial. BMC Med. 2023 Aug 15;21(1):306. doi: 10.1186/s12916-023-03017-z.

  PMID: 37580773 DERIVED

• Yap YS, Chiu J, Ito Y, Ishikawa T, Aruga T, Kim SJ, Toyama T, Saeki T, Saito M, Gounaris I, Su F, Ji Y, Han Y, Gazdoiu M, Masuda N. Ribociclib, a CDK 4/6 inhibitor, plus endocrine therapy in Asian women with advanced breast cancer. Cancer Sci. 2020 Sep;111(9):3313-3326. doi: 10.1111/cas.14554. Epub 2020 Jul 28.

  PMID: 32619077 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

ribociclib; Letrozole; Tamoxifen; Fulvestrant; Goserelin

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2015
• First Posted: January 7, 2015
• Study Start: February 4, 2015
• Primary Completion: September 29, 2022
• Study Completion: September 29, 2022
• Last Updated: June 8, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); JP (13); SG (1)