Montag, 6. Mai 2024
Navigation öffnen
Anzeige:
Wefra Programatic
 
JOURNAL ONKOLOGIE – STUDIE
PREcoopERA

A Window-of-Opportunity Trial of Giredestrant +/- Triptorelin vs. Anastrozole + Triptorelin in Premenopausal Patients With ER-positive/HER2-negative Early Breast Cancer

Rekrutierend

NCT-Nummer:
NCT05896566

Studienbeginn:
Januar 2024

Letztes Update:
05.04.2024

Wirkstoff:
Giredestrant, Triptorelin, Anastrozole

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
ETOP IBCSG Partners Foundation

Collaborator:
Hoffmann-La Roche

Studienleiter

Elisabetta Munzone, MD
Study Chair
European Institute of Oncology, Milano

Kontakt

Studienlocations
(3 von 44)

Darmkrebszentrum am Universitätsklinikum Schleswig-Holstein, Campus Lübeck
Ratzeburger Allee 160
23562 Lübeck
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Marion van Mackelenbergh
E-Mail: MarionTina.vanMackelenbergh@uksh.de» Ansprechpartner anzeigen
Pankreaskarzinomzentrum am Klinikum Südstadt Rostock
Südring 81
18059 Rostock
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Toralf Reimer
E-Mail: toralf.reimer@kliniksued-rostock.de» Ansprechpartner anzeigen
Leberkrebszentrum Universitätsklinikum Ulm
Albert-Einstein-Allee 23
89081 Ulm
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Brigitte Rack
E-Mail: Rack_Studien.UFK@uniklinik-ulm.de» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

The primary objectives are:

- to determine if 4 weeks of giredestrant plus triptorelin provides greater

anti-proliferative activity than anastrozole plus triptorelin among premenopausal

patients with ER-positive/HER2-negative operable invasive breast cancer.

- to determine if 4 weeks of giredestrant without triptorelin provides anti-proliferative

activity that is similar (non-inferior) to giredestrant plus triptorelin among

premenopausal patients with ER-positive/HER2-negative operable invasive breast cancer.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Premenopausal women age ≥18 years, premenopausal status defined as:

Estradiol (E2) in the premenopausal range (according to institution parameters) or Patient

has been menstruating regularly during the 6 months prior to screening and has not used any

form of hormonal contraception or any other hormonal treatments during this time.

- Histologically confirmed, operable invasive breast carcinoma.

- Eligible for upfront breast conservative surgery or upfront mastectomy: stage I, stage

II or operable stage III (excludes T4) (AJCC Cancer Staging Manual 8th edition

2017).46 Tumor size must be ≥1.0 cm Multicentric and multifocal tumors and bilateral

breast cancers are allowed but investigators must ensure the same tumor foci is

biopsied pre-treatment and post-treatment (e.g., via clipping of the biopsied tumor

foci).

- Documented estrogen receptor (ER)-positive tumor in accordance to ASCO/CAP guidelines

(Allison et al. 2020),47 assessed locally and defined as ≥1% of tumor cells stained

positive.

- Documented human epidermal growth factor receptor-2 (HER2)-negative tumor in

accordance to 2018 ASCO/CAP guidelines (Wolff et al. 2018)48, as determined per local

assessment.

- Ki 67 ≥10% in diagnostic biopsy as determined per local assessment.

- Eastern Cooperative Oncology Group Performance Status 0-1.

- Resting heart rate ≥40 bpm.

- Normal hematologic status

- Normal renal function

- Normal liver function

- INR <1.5× ULN and PTT <1.5x ULN Except for patients receiving anticoagulation therapy.

For patients receiving warfarin, a stable INR between 2 and 3 is required. For

patients receiving heparin, PTT between 1.5 and 2.5 x ULN (or value before patient

started heparin treatment) is required.

If anticoagulation therapy is required for a prosthetic heart valve, stable INR between 2.5

and 3.5 is permitted.

- Negative serum or urine beta HCG pregnancy test within 5 weeks prior to randomization.

Pregnancy test will be repeated on day 1, before the first dose of WOO treatment.

Women of childbearing potential must use highly effective contraceptive methods during the

treatment period and for 10 days after the final dose.

- Written Informed Consent (IC) must be signed and dated by the patient and the

Investigator prior to randomization.

- The patient has been informed of and agrees to data transfer and handling, in

accordance with national data protection guidelines.

- The patient agrees to the submission of tumor (diagnostic pre-treatment core biopsy

and post-treatment re-biopsy) and blood samples for central pathology review (CPR) and

for translational studies as part of this protocol.

Exclusion Criteria:

- Stage IV (metastatic) breast cancer.

- Inflammatory breast cancer (cT4d).

- Previous systemic or local treatment for the primary breast cancer currently under

investigation.

- Received any GnRH/LHRH analog within 12 months prior to randomization

- Major surgery within 4 weeks prior to randomization.

- Known clinically significant history of liver disease consistent with Child-Pugh Class

B or C, including hepatitis.

- Other severe acute or chronic medical or psychiatric condition or laboratory

abnormality that may increase the risk associated with study participation or

investigational product administration or may interfere with the interpretation of

study results and, in the judgment of the investigator, would make the patient

inappropriate for entry into this study.

- History of documented hemorrhagic diathesis, coagulopathy, or thromboembolism.

- Active cardiac disease or history of cardiac dysfunction, including any of the

following:

History or presence of symptomatic bradycardia or resting heart rate <50 bpm at screening.

Patients on stable dose of a beta-blocker or calcium channel antagonist for pre-existing

baseline conditions (e.g., hypertension) may be permitted if resting heart rate is ≥50 bpm.

History of angina pectoris, symptomatic pericarditis, myocardial infarction, or any cardiac

arrhythmias (e.g., ventricular, supraventricular, nodal arrhythmias, or conduction

abnormality) within 12 months prior to study entry History of documented congestive heart

failure (New York Heart Association Class II-IV) or cardiomyopathy Left ventricular

ejection fraction <50% as determined by multiple-gated acquisition scan or echocardiogram

QT interval corrected through use of Fridericia's formula (QTcF) >470 ms based on mean

value of triplicate ECGs, history of long or short QT syndrome, Brugada syndrome or known

history of corrected QT interval prolongation, or torsades de pointes History or presence

of an abnormal ECG that is clinically significant in the investigator's opinion, including

complete left bundle branch block, second- or third-degree heart block, sick sinus

syndrome, or evidence of prior myocardial infarction

- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such

as structural heart disease (e.g., severe left ventricular systolic dysfunction, left

ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia

demonstrated by diagnostic testing), clinically significant electrolyte abnormalities

(e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of long QT

syndrome.

- Current treatment with medications that are well known to prolong the QT interval.

- Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug

elimination half-lives (whichever is longer) prior to initiation of study treatment.

- Known issues with swallowing oral medication.

- Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or major

upper gastrointestinal surgery including gastric resection.

- Serious infection requiring oral or IV antibiotics, or other clinically significant

infection within 14 days prior to screening.

- Any active tumor of non-breast-cancer histology.

- Women who are pregnant or in the period of lactating.

- Any concurrent disease or serious medical condition or abnormality in clinical

laboratory tests that, in the investigator's judgment, precludes the patient's safe

participation in and completion of the study.

- Judgement by the investigator that the patient should not participate in the study if

the patient is unlikely to comply with study procedures, restrictions and

requirements.

- Contraindications or known hypersensitivity to the trial medication or excipients.

- Treatment with any investigational agents within 30 days prior to expected start of

trial treatment.

Studien-Rationale

Primary outcome:

1. Change in Ki 67 (Time Frame - From date of randomisation until 29 ±3 days post-randomisation):
The primary endpoint is the change in Ki 67 (Ki 67-labeling index, the percentage immunostaining cells measured by IHC in central laboratory) between the pre-treatment tumor biopsy and a post-treatment tumor re-biopsy (analyzed on the natural logarithm scale).



Secondary outcome:

1. Complete cell cycle arrest (CCCA) (Time Frame - From date of randomisation until 29 ±3 days post-randomisation):
Complete cell cycle arrest (CCCA), defined as Ki 67 ≤2.7% on the post -treatment tumor re-biopsy on day 29 (±3 days), by visual image analysis.

2. Adverse events according to CTCAE v5.0 (Time Frame - From the date of enrolment until last patient last visit (approximately 28 months after randomisation of the first patient)]):
Record all AEs (including SAEs and AESIs) and assign the appropriate grade according to the CTCAE v5.0.

Studien-Arme

  • Experimental: Arm A: Giredestrant
    Giredestrant
  • Experimental: Arm B: Giredestrant plus triptorelin
    Giredestrant plus triptorelin
  • Active Comparator: Arm C: Anastrozole plus triptorelin
    Anastrozole plus triptorelin

Geprüfte Regime

  • Giredestrant:
    Giredestrant: 30 mg daily, PO from day 1 until the day of re-biopsy/surgery.
  • Triptorelin:
    Triptorelin: 3.75 mg IM on day 1. Note: If re-biopsy/surgery cannot be done on day 29 (±3 days) from the first injection, then a second dose of triptorelin should be given on day 29 (±3 days).
  • Anastrozole:
    Anastrozole: 1 mg daily, PO from day 1 until the day of re-biopsy/surgery.

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"A Window-of-Opportunity Trial of Giredestrant +/- Triptorelin vs. Anastrozole + Triptorelin in Premenopausal Patients With ER-positive/HER2-negative Early Breast Cancer"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!

Die Verwendung Ihrer Daten für den Newsletter können Sie jederzeit mit Wirkung für die Zukunft gegenüber der MedtriX GmbH - Geschäftsbereich rs media widersprechen ohne dass Kosten entstehen. Nutzen Sie hierfür etwaige Abmeldelinks im Newsletter oder schreiben Sie eine E-Mail an: rgb-info[at]medtrix.group.