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AMALEE: Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03822468
Collaborator
(none)
376
Enrollment
92
Locations
2
Arms
78.7
Anticipated Duration (Months)
4.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

QT interval prolongation and neutropenia are considered to be important identified risks for ribociclib. The approved dosing regimen of ribociclib is 600 mg daily (QD) on a 3 weeks on/1 week off schedule.

The purpose of the study is to explore whether a reduced dosing regimen of 400 mg ribociclib orally QD 3 weeks on/1 week off may decrease the risk of QTc prolongation without compromising the efficacy of ribociclib in combination with an NSAI in pre- and postmenopausal women with HR-positive, HER2-negative aBC who have received no prior therapy for advanced disease. The risks of other AEs of special interest, such as neutropenia and hepatobiliary toxicity will be evaluated in this study as well.

Approximately 350 patients will be randomly assigned to one of the below treatment arms in a 1:1 ratio: Experimental arm (Arm 1) - Ribociclib 400 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Control arm (Arm 2) - Ribociclib 600 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Randomization will be stratified by the presence of lung and/or liver metastases (yes versus no).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
376 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Multicenter, Randomized, Open-label Study to Evaluate the Safety and Efficacy of 400 mg of Ribociclib in Combination With Non-steroidal Aromatase Inhibitors for the Treatment of Pre- and Postmenopausal Women With Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease
Actual Study Start Date :
Jun 11, 2019
Actual Primary Completion Date :
Jun 11, 2021
Anticipated Study Completion Date :
Dec 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ribociclib 400 mg

Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)

Drug: Ribociclib
Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.
Other Names:
  • LEE011

    • Drug: Letrozole or Anastrozole
    Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)

    Drug: Goserelin
    Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)
    Active Comparator: Ribociclib 600 mg

    Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)

    Drug: Ribociclib
    Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.
    Other Names:
  • LEE011

    • Drug: Letrozole or Anastrozole
    Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)

    Drug: Goserelin
    Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [At least 6 months]

      ORR is based on local tumor assessments (RECIST version 1.1) for all patients that have been treated for at least 6 months or have discontinued the study treatment.

    Secondary Outcome Measures

    1. Δ QTcF at Cycle 1 Day 15 (at 2h post-dose) (Key Secondary Endpoint) [Cycle 1 Day 15 (2 hours post dose)]

      To evaluate QTc (with Fridericia's correction) prolongation in the experimental arm

    2. Progression-free survival (PFS) [Approximately 36 months]

      PFS per RECIST 1.1

    3. Clinical benefit rate (CBR) [Approximately 36 months]

      CBR per RECIST 1.1

    4. Time to response (TTR) [Approximately 36 months]

      TTR per RECIST 1.1

    5. Duration of response (DOR) [Approximately 36 months]

      DOR per RECIST 1.1

    6. Pharmacokinetics (PK) of ribociclib: Cmax [Cycle 1 Day 15]

      when given in combination with NSAI

    7. Pharmacokinetics (PK) of ribociclib: Tmax [Cycle 1 Day 15]

      when given in combination with NSAI

    8. Pharmacokinetics (PK) of ribociclib: AUC0 - 24h [Cycle 1 Day 15]

      when given in combination with NSAI

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Key Inclusion criteria:

    Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable to curative therapy.

    Patient has a histologically and/or cytologically confirmed diagnosis of ER-positive and/or PgR-positive breast cancer based on the most recently analyzed tissue sample, and all tested by local laboratory.

    Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample.

    Patient must have measurable disease, i.e., at least one measurable lesion according to RECIST version 1.1. (a lesion in a previously irradiated site may only be counted as a target lesion if there is clear evidence of progression since the irradiation).

    Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

    Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory:

    • QTcF interval at screening < 450 ms (QT interval using Fridericia's correction)

    • Mean resting heart rate 50 to 90 bpm (determined from the ECG)

    Women of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant, must have confirmed negative serum pregnancy test (for β-hCG) within 14 days prior to randomization.

    Women of CBP must be willing to use highly effective methods of contraception.

    Key Exclusion Criteria:

    Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's judgment.

    Patient who received any prior systemic anti-cancer therapy(including endocrine therapy, chemotherapy, prior CDK4/6 inhibitors) for aBC. Patients who received neo-/adjuvant therapy for breast cancer are eligible.

    Patient is concurrently using other anti-cancer therapy.

    Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major toxicities.

    Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization, and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). Patients in whom ≥ 25% of the bone marrow has been previously irradiated are also excluded.

    Patient has a concurrent malignancy or malignancy within 3 years of the randomization date, with the exception of adequately treated basal or squamous cell skin carcinoma, or curatively resected cervical carcinoma in situ.

    Patients with central nervous system (CNS) involvement unless they meet specific stability criteria.

    Patient has clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.

    Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, and has not fully recovered from side effects of such treatment.

    Other protocol-defined Inclusion/Exclusion may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Southern Cancer Center PC Mobile Alabama United States 36608
    2 Marin Cancer Care Greenbrae California United States 94904
    3 Rocky Mountain Cancer Centers Rocky Mountain Cancer Ctr (50) Denver Colorado United States 80501
    4 Florida Retina Institute Orlando Florida United States 32804
    5 Emory University School of Medicine/Winship Cancer Institute Atlanta Georgia United States 30322
    6 Weinberg Cancer Institute at Franklin Square Hospital Baltimore Maryland United States 21237-3998
    7 Nebraska Hematology-Oncology, P.C. Lincoln Nebraska United States 68506
    8 Nebraska Cancer Specialists Oncology Hematology West Omaha Nebraska United States 68154
    9 Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4) Las Vegas Nevada United States 89109
    10 New York Oncology Hematology SC Albany New York United States 12208
    11 Montefiore Medical Center Bronx New York United States 10467
    12 Mount Sinai School of Medicine CFTY720D2306 New York New York United States 10029
    13 Northwest Cancer Ctr Houston Texas United States 77090
    14 Texas Oncology McAllen Texas United States 78503
    15 Northwest Medical Specialties Dept.ofNW Med. Specialties Tacoma Washington United States 98405
    16 Novartis Investigative Site San Juan Argentina J5402DIL
    17 Novartis Investigative Site Innsbruck Austria A-6020
    18 Novartis Investigative Site Linz Austria 4010
    19 Novartis Investigative Site Salzburg Austria 5020
    20 Novartis Investigative Site Vienna Austria 1090
    21 Novartis Investigative Site Edegem Antwerpen Belgium 2650
    22 Novartis Investigative Site Namur Belgium 5000
    23 Novartis Investigative Site Goiania GO Brazil 74605-070
    24 Novartis Investigative Site Natal RN Brazil 59075 740
    25 Novartis Investigative Site Florianopolis Santa Catarina Brazil 88034 000
    26 Novartis Investigative Site Sao Paulo SP Brazil 01317 000
    27 Novartis Investigative Site Sao Paulo SP Brazil 03102-002
    28 Novartis Investigative Site Sao Jose do Rio Preto Brazil 15090 000
    29 Novartis Investigative Site Plovdiv Bulgaria 4004
    30 Novartis Investigative Site Sofia Bulgaria 1303
    31 Novartis Investigative Site Sofia Bulgaria 1756
    32 Novartis Investigative Site Cambridge Ontario Canada N1R 3G2
    33 Novartis Investigative Site Valledupar Cesar Colombia 5602310
    34 Novartis Investigative Site Ibague Tolima Colombia 730006
    35 Novartis Investigative Site Bogota Colombia 110221
    36 Novartis Investigative Site Bogota Colombia
    37 Novartis Investigative Site Monteria Colombia 230002
    38 Novartis Investigative Site San Jose Costa Rica
    39 Novartis Investigative Site Brno Czech Republic Czechia 656 53
    40 Novartis Investigative Site Praha 5 Czechia 150 06
    41 Novartis Investigative Site Helsinki Finland 00029
    42 Novartis Investigative Site Tampere Finland FIN-33521
    43 Novartis Investigative Site Besancon Cedex France 25030
    44 Novartis Investigative Site Caen Cedex France 14021
    45 Novartis Investigative Site Clermont Ferrand France 63011
    46 Novartis Investigative Site Lyon Cedex 08 France 69373
    47 Novartis Investigative Site Marseille France 13273
    48 Novartis Investigative Site Montpellier Cedex 5 France 34298
    49 Novartis Investigative Site Saint Herblain cedex France 44805
    50 Novartis Investigative Site Strasbourg France F 67085
    51 Novartis Investigative Site Valenciennes France 59300
    52 Novartis Investigative Site Langen Hessen Germany 63225
    53 Novartis Investigative Site Augsburg Germany 86150
    54 Novartis Investigative Site Berlin Germany 13581
    55 Novartis Investigative Site Bonn Germany 53111
    56 Novartis Investigative Site Dresden Germany 01127
    57 Novartis Investigative Site Dresden Germany 01307
    58 Novartis Investigative Site Essen Germany 45136
    59 Novartis Investigative Site Tübingen Germany 72076
    60 Novartis Investigative Site Weiden Germany 92637
    61 Novartis Investigative Site Budapest Hungary H 1122
    62 Novartis Investigative Site Debrecen Hungary 4032
    63 Novartis Investigative Site Szolnok Hungary H-5000
    64 Novartis Investigative Site Raipur Chhattisgarh India 492001
    65 Novartis Investigative Site Nagpur Maharashtra India 441108
    66 Novartis Investigative Site Bhubaneshwar Orissa India 751007
    67 Novartis Investigative Site Delhii India 110 085
    68 Novartis Investigative Site Mumbai India 400 012
    69 Novartis Investigative Site Amman Jordan 11941
    70 Novartis Investigative Site Kaunas LTU Lithuania LT 50161
    71 Novartis Investigative Site Vilnius Lithuania LT-08660
    72 Novartis Investigative Site Trujillo La Libertad Peru
    73 Novartis Investigative Site San Borja Lima Peru 41
    74 Novartis Investigative Site San Isidro Lima Peru 27
    75 Novartis Investigative Site San Miguel Lima Peru 32
    76 Novartis Investigative Site Arequipa Peru
    77 Novartis Investigative Site Lisbon Portugal 1400 038
    78 Novartis Investigative Site Loures Portugal 2674514
    79 Novartis Investigative Site Porto Portugal 4200-072
    80 Novartis Investigative Site Arkhangelsk Russian Federation 163045
    81 Novartis Investigative Site Moscow Russian Federation 111123
    82 Novartis Investigative Site Moscow Russian Federation 115478
    83 Novartis Investigative Site St Petersburg Russian Federation 197758
    84 Novartis Investigative Site St-Petersburg Russian Federation 189646
    85 Novartis Investigative Site Cape Town South Africa 7500
    86 Novartis Investigative Site Johannesburg South Africa 2196
    87 Novartis Investigative Site Parktown South Africa 2193
    88 Novartis Investigative Site Stockholm Sweden 112 19
    89 Novartis Investigative Site Stockholm Sweden SE-118 83
    90 Novartis Investigative Site Uppsala Sweden 751 85
    91 Novartis Investigative Site Bangkok Thailand 10700
    92 Novartis Investigative Site Chiang Mai Thailand 50200

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03822468
    Other Study ID Numbers:
    • CLEE011A2207
    • 2018-004234-15
    First Posted:
    Jan 30, 2019
    Last Update Posted:
    May 13, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Breast Cancer
    HR-positive
    HER2-negative
    ER-positive
    advanced breast cancer
    ribociclib
    LEE011
    premenopausal
    postmenopausal
    Additional relevant MeSH terms:
    Breast Neoplasms
    Letrozole
    Anastrozole
    Goserelin

    Study Results

    No Results Posted as of May 13, 2022