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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03822468

Studienbeginn:
Juni 2019

Letztes Update:
19.12.2020

Wirkstoff:
Ribociclib, Letrozole or Anastrozole, Goserelin

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals

Kontakt

Studienlocations (3 von 108)

Novartis Investigative Site
80637 Muenchen
(Bayern)
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Novartis Investigative Site
63225 Langen
(Hessen)
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Novartis Investigative Site
42551 Velbert
(Nordrhein-Westfalen)
GermanyZurückgezogen» Google-Maps
Novartis Investigative Site
23563 Luebeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
86150 Augsburg
(Bayern)
GermanyRekrutierend» Google-Maps
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13581 Berlin
(Berlin)
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Novartis Investigative Site
53111 Bonn
(Nordrhein-Westfalen)
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01127 Dresden
(Sachsen)
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01307 Dresden
(Sachsen)
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45136 Essen
(Nordrhein-Westfalen)
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Novartis Investigative Site
72076 Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
92637 Weiden
(Bayern)
GermanyRekrutierend» Google-Maps
Rocky Mountain Cancer Centers Rocky Mountain Cancer Ctr (50)
80111 Greenwood Village
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Rebecca Desjarlais
Phone: 714-835-1800
E-Mail: rebecca.desjarlais@usoncology.com
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Weinberg Cancer Institute at Franklin Square Hospital
21237-3998 Baltimore
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Sally Brown
Phone: 443-777-7364
E-Mail: sally.brown@medstar.net
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Nebraska Hematology-Oncology, P.C.
68506 Lincoln
United StatesAktiv, nicht rekrutierend» Google-Maps
Nebraska Cancer Specialists Oncology Hematology West
68154 Omaha
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Marsha Ketcham
Phone: +1 402 334 4773
E-Mail: mketcham@nebraskacancer.com
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Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)
89109 Las Vegas
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Khin Win
Phone: 702-856-1401
E-Mail: Khin.Win@usoncology.com
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Mount Sinai School of Medicine CFTY720D2306
10029 New York
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Christopher Hickson
Phone: 212-241-4264
E-Mail: christopher.hickson@mssm.edu
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Novartis Investigative Site
C1280AEB Caba
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J5402DIL San Juan
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A-6020 Innsbruck
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1200 Bruxelles
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1340 Ottignies
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74605-070 Goiania
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59075 740 Natal
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88034 000 Florianopolis
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01317 000 Sao Paulo
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Novartis Investigative Site
03102-002 Sao Paulo
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15090 000 Sao Jose do Rio Preto
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N1R 3G2 Cambridge
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P3E 5J1 Sudbury
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5602310 Valledupar
ColombiaRekrutierend» Google-Maps
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730006 Ibague
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110221 Bogota
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230002 Monteria
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San Jose
Costa RicaAktiv, nicht rekrutierend» Google-Maps
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656 53 Brno
CzechiaAktiv, nicht rekrutierend» Google-Maps
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150 06 Praha 5
CzechiaAktiv, nicht rekrutierend» Google-Maps
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00029 Helsinki
FinlandAktiv, nicht rekrutierend» Google-Maps
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FIN-33521 Tampere
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25030 Besancon Cedex
FranceAktiv, nicht rekrutierend» Google-Maps
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14021 Caen Cedex
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63011 Clermont-Ferrand
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69373 Lyon Cedex 08
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13273 Marseille
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34298 Montpellier Cedex 5
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44805 Saint Herblain cedex
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F 67085 Strasbourg
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59300 Valenciennes
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H 1122 Budapest
HungaryAktiv, nicht rekrutierend» Google-Maps
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4032 Debrecen
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H-5000 Szolnok
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600035 Tamil Nadu
IndiaRekrutierend» Google-Maps
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751007 Bhubaneshwar
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11941 Amman
JordanAktiv, nicht rekrutierend» Google-Maps
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LT 50161 Kaunas
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LT-08660 Vilnius
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Trujillo
PeruAktiv, nicht rekrutierend» Google-Maps
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41 San Borja
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27 San Isidro
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32 San Miguel
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Arequipa
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1400 038 Lisbon
PortugalAktiv, nicht rekrutierend» Google-Maps
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2674514 Loures
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Novartis Investigative Site
4200-072 Porto
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163045 Arkhangelsk
Russian FederationAktiv, nicht rekrutierend» Google-Maps
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111123 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
115478 Moscow
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197758 St Petersburg
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
189646 St-Petersburg
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
7500 Cape Town
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2196 Johannesburg
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2193 Parktown
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Novartis Investigative Site
112 19 Stockholm
SwedenAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
SE-118 83 Stockholm
SwedenAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
751 85 Uppsala
SwedenAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
SE-351 85 Vaxjo
SwedenZurückgezogen» Google-Maps
Novartis Investigative Site
10700 Bangkok
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Novartis Investigative Site
50200 Chiang Mai
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Studien-Informationen

Brief Summary:

QT interval prolongation and neutropenia are considered to be important identified risks for

ribociclib (Kisqali® Prescribing Information, Investigator Brochure). 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).

Ein-/Ausschlusskriterien

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:

- QTc interval at screening < 450 ms (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).

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.

Studien-Rationale

Primary outcome:

1. Overall Response Rate (ORR) (Time Frame - 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:

1. Δ QTcF at Cycle 1 Day 15 (at 2h post-dose) (Key Secondary Endpoint) (Time Frame - 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) (Time Frame - Approximately 36 months):
PFS per RECIST 1.1

3. Clinical benefit rate (CBR) (Time Frame - Approximately 36 months):
CBR per RECIST 1.1

4. Time to response (TTR) (Time Frame - Approximately 36 months):
TTR per RECIST 1.1

5. Duration of response (DOR) (Time Frame - Approximately 36 months):
DOR per RECIST 1.1

6. Pharmacokinetics (PK) of ribociclib: Cmax (Time Frame - Cycle 1 Day 15):
when given in combination with NSAI

7. Pharmacokinetics (PK) of ribociclib: Tmax (Time Frame - Cycle 1 Day 15):
when given in combination with NSAI

8. Pharmacokinetics (PK) of ribociclib: AUC0 - 24h (Time Frame - Cycle 1 Day 15):
when given in combination with NSAI

Studien-Arme

  • Experimental: Ribociclib 400 mg
    Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
  • Active Comparator: Ribociclib 600 mg
    Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)

Geprüfte Regime

  • Ribociclib (LEE011):
    Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.
  • Letrozole or Anastrozole:
    Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)
  • Goserelin:
    Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

Quelle: ClinicalTrials.gov


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