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Hormone Receptor Positive, HER2-negative, Advanced Breast CancerPhase 1NCT02333370

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

A Phase 1 study testing LEE011, Letrozole and Tamoxifen in people with Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer, run by Novartis Pharmaceuticals at 15 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
LEE011, Letrozole and Tamoxifen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
15 sitesin 3 countries
Study dates
4 Feb 2015to 29 Sep 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 11Show fewer
  • 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

Trial locations and contacts

15 sites in 3 countries.

15 sites in 3 countries

Japan13 sites

  • Novartis Investigative Site

    Bunkyo Ku, Tokyo, 113-8431

  • Novartis Investigative Site

    Bunkyo Ku, Tokyo, 113-8677

  • Novartis Investigative Site

    Hidaka, Saitama, 350-1298

  • Novartis Investigative Site

    Kitaadachi-gun, Saitama, 362-0806

  • Novartis Investigative Site

    Koto Ku, Tokyo, 135 8550

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 467-8602

  • Novartis Investigative Site

    Osaka, Osaka, 540-0006

  • Novartis Investigative Site

    Sapporo, Hokkaido, 003-0804

  • Novartis Investigative Site

    Shinagawa-ku, Tokyo, 142-8666

  • Novartis Investigative Site

    Shinjuku-ku, Tokyo, 160-0023

  • Novartis Investigative Site

    Suita, Osaka, 565 0871

  • Novartis Investigative Site

    Sunto Gun, Shizuoka, 411 8777

  • Novartis Investigative Site

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

Singapore1 site

  • Novartis Investigative Site

    Singapore, 168583

Other trials in Singapore

About this study

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.
Being tested
LEE011, Letrozole, Tamoxifen, Fulvestrant, goserelin
Keywords
Advanced breast cancer, Hormone receptor positive, HER2-negative, LEE011,, Letrozole, Tamoxifen, Fulvestrant, Postmenopausal Asian women, Pre and Postmenopausal Japanese women

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LEE011Drug

    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.

  • LetrozoleDrug

    25mg

  • TamoxifenDrug

    20 mg

  • FulvestrantDrug

    500 mg

  • goserelinDrug

Study groups in NCT02333370
Study groupRoleWhat they receive
LEE011 +LetrozoleExperimentalLEE011 - 3 weeks on 1 week off Letrozole 2.5mg - Once daily
Receives: Drug: LEE011; Drug: Letrozole
LEE011 + TamoxifenExperimentalLEE011 - 3 weeks on 1 week off Tamoxifen 20mg - Once daily
Receives: Drug: Tamoxifen; Drug: goserelin
LEE011 + FulvestrantExperimentalLEE011 - 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
Receives: Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: first cycle (28 days)

  2. 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

    Measured: 18 months

  3. 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

    Measured: 18 months

Secondary outcomes (9)

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

    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

    Measured: 18 months

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

    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

    Measured: 18 months

  3. Overall Response Rate (ORR) - Phase Ib dose expansion

    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

    Measured: 18 months

  4. Clinical Benefit Rate (CBR) - Phase Ib dose expansion

    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

    Measured: 18 months

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

    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

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

  6. Progression Free Survival (PFS) as per RECIST v1.1- phase Ib dose expansion

    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

    Measured: 18 months

  7. Overall Survival (OS) - Phase Ib dose expansion

    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

    Measured: 18 months

  8. Disease Control Rate (DCR) - Phase Ib dose expansion

    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

    Measured: 18 months

  9. Duration of Response (DOR) - Phase Ib dose expansion

    Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2015 (estimated)
  2. Study start4 Feb 2015
  3. Primary completion29 Sep 2022
  4. Study completion29 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
88 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02333370
Sponsor's protocol ID
CLEE011A2115C
Status last verified
Jun 2023
First submitted
5 Jan 2015
Last updated
8 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37580773

  • 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.

    PubMed 32619077

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LEE011, Letrozole and Tamoxifen in people with Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer, run by Novartis Pharmaceuticals at 15 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Japan, Hong Kong, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs) (time frame: first cycle (28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02333370, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2023.

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