Trial Title:
NEOadjuvant Abemaciclib and GIredestrant triaL in Patients With ER-positive, HER2-negative Early Breast Cancer
NCT ID:
NCT06259929
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Abemaciclib 150 MG + Giredestrant 30 MG
Description:
Enrolled patients will receive 6 cycles of treatment in the absence of disease
progression or unacceptable toxicity for a total of 24 weeks (2 weeks of opportunity
phase and 22 weeks of neoadjuvant phase) before surgery
Arm group label:
Patients with ER-positive, HER2-negative Early breast cancer
Summary:
The objective of the study is to evaluate the efficacy and the safety of abemaciclib and
giredestrant before surgery in participants with early stage, oestrogen receptor-positive
(ER+), human epidermal receptor 2 negative (HER2-) breast cancer (BC).
Primary objective:
● To evaluate the efficacy of abemaciclib and giredestrant in complete cell cycle arrest
(CCCA) rate at Week 2.
Secondary objectives:
- To evaluate the efficacy of abemaciclib and giredestrant in reducing the relative
Ki67 expression from baseline to Week 2
- To evaluate the efficacy of abemaciclib and giredestrant in risk of recurrence (ROR)
score reduction, clinical and radiological tumor response;
- To evaluate the safety of abemaciclib and giredestrant.
Exploratory objectives:
- To evaluate the mechanisms of response and resistance to therapy;
- To evaluate the correlation between Ki-67% reduction and 18- Fluorothymidine (FLT)
uptake reduction;
- To evaluate the pathological complete response (pCR) rate (ypT0/is, ypN0) of
giredestrant plus abemaciclib
Detailed description:
This is a phase II, multicentre, single-arm neoadjuvant study in post- menopausal women
with ER-positive and HER2-previously untreated early BC. The trial will include
approximately 10 sites in Italy.
The study plan will include a maximum 28-day screening period prior to start treatment.
During the 6 cycles of the on-study intervention period, participants will return to the
clinic every 2 weeks (14 ± 3 days) for the first 2 cycles, and then on Day 1 of the
subsequent 4 cycles.
Surgery should be performed as soon as possible after at least 7 days, from the last dose
of abemaciclib and giredestrant, and no later than 30 days.
During the short-term follow-up, participants should return for an in-clinic visit 28
days (± 5 days) after surgery. After the short-term follow-up visit, all participants
will enter the long-term follow-up period, which will begin the day after the short-term
follow-up visit and will continue up to Year1. Visits during the long-term follow-up
visits should occur approximately every 3 months for a total of one year. For
participants who are unable to attend the required clinic visits, long-term follow-up
visits can take place as a phone visit.
Blood and tumor samples will be used to investigate the mechanisms of response and
resistance to therapy in ER+ and HER2- early BC. For each patient enrolled in the present
study, blood samples (mandatory) and tumor biopsies (mandatory) are required and
collected at entry in the study, following 14 days and 12 weeks of treatment, and prior
to or during surgery. Blood samples are also required to be collected at the short follow
up visit, at the end of the long follow-up period after on year (± 28 days) from the last
short follow-up visit and at disease progression (suggested but not mandatory).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Female patients willing and able to give written informed consent;
2. Women≥18 years of age;
3. Postmenopausal women, as defined by at least one of the following criteria:
- ≥12 months of amenorrhea without an alternate medical cause plus
follicle-stimulating hormone (FSH) and plasma estradiol levels within
postmenopausal range by local laboratory assessment, in the absence of oral
contraceptive pills, hormone replacement therapy, or gonadotropin-releasing
hormone agonist or antagonist. However, in the absence of 12 months of
amenorrhea, a single FSH measurement is insufficient;
- Documented bilateral oophorectomy (≥ 14 days prior to first treatment on Day 1
of Cycle 1 and recovery from surgery to baseline);
4. Patients with cT1c (≥1.0 cm)-cT4a-c BC at presentation; a-c primary tumor must be ≥
1.0 cm in longest diameter by ultrasound;
5. Confirmed ER+ disease by local testing on primary disease specimen: tumor must be ER
≥ 10% defined by immunohistochemistry (IHC) according to American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for
hormone receptor testing;
6. Confirmed HER2- disease by local testing on primary disease specimen: tumor must be
HER2- according to ASCO/CAP 2023 guidelines for HER2 testing;
7. Patients with multifocal or multicentric breast cancer with at least one tumor
lesion ≥1.0 cm in the longest diameter by ultrasound (reference lesion) are also
eligible if the two largest tumor lesions have been histologically confirmed in the
clinical evaluation and meet pathologic criteria for ER positivity and HER2
negativity.
8. No previous treatment of the disease by chemotherapy, hormone therapy, surgery or
radiotherapy;
9. Patients considered appropriate for endocrine therapy according to physician
judgment;
10. Ki67 score ≥10% analyzed locally and centrally confirmed. Ki67 will be analyzed
locally at the time of inclusion. Patients with basal Ki67≥20% will be assessed
locally and centrally confirmed retrospectively and patients with 10-19% will be
assessed centrally before inclusion.
11. Patients with breast cancer eligible for primary surgery;
12. Eastern Cooperative Oncology Group (ECOG) performance status≤1;
13. Adequate bone marrow and coagulation and adequate organ function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
- Platelets count ≥100x 109/L;
- Haemoglobin ≥9 g/dL (90 g/L);
- Serum creatinine≤1.5 x upper limit of normal (ULN) or estimated creatinine
clearance≥60 ml/min as calculated using the standard method for the
institution;
- Total serum bilirubin ≤1.5 x ULN (Patients with Gilbert's syndrome with a total
bilirubin ≤2.0 times ULN and direct bilirubin within normal limits could be
included);
- AST and/or ALT ≤3 x ULN;
- Alkaline phosphatase ≤2.5 x ULN;
14. Patients able to swallow oral medications.
Exclusion Criteria:
1. Patients with bilateral invasive BC;
2. Patients with metastatic BC (local spread to axillary lymph nodes is permitted
(cN1_cN2a);
3. Patients with inflammatory BC;
4. Non post-menopausal patients;
5. Patients having received previous systemic or local treatment for BC, in particular
history of any prior treatment with aromatase inhibitors (AIs), tamoxifen, selective
estrogen receptor down regulator, or cyclin-dependent kinase 4 and 6 inhibitors;
6. Participants who have active cardiac disease or history of cardiac dysfunction,
including any of the following:
- History (within 2 years of screening) or presence of idiopathic bradycardia or
resting heart rate < 50 beats per minute at screening
- History of angina pectoris or symptomatic coronary heart disease within 12
months prior to randomization
- History of documented congestive heart failure (New York Heart Association
Class III or IV) or cardiomyopathy
- QT interval corrected through use of Fridericia's formula >470 ms for women >
450 ms for men 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
- 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, or sick sinus syndrome o Participants with
first-degree heart block may be considered for inclusion following consultation
with a cardiologist and determination that no additional cardiac risks are
present.
- Participants with pacemakers to treat more severe heart blocks and other
arrhythmias are permitted.
- Patients with history of well-controlled atrial fibrillation are eligible.
- History (within 12 months) or presence of ventricular dysrhythmias or risk
factors for ventricular dysrhythmias, such as significant structural heart
disease (e.g., severe left ventricular systolic dysfunction, restrictive
cardiomyopathy, hypertrophic cardiomyopathy, infiltrative cardiomyopathy,
moderate-to-severe valve disease), or family history of long QT syndrome) o
Clinically significant electrolyte abnormalities (e.g., hypokalemia,
hypomagnesemia, hypocalcemia) should be corrected prior to enrollment.
7. Patients with known clinically significant history of liver disease consistent with
Child-Pugh Class B or C, including hepatitis;
8. Patients with history of invasive BC, ductal carcinoma in situ or lobular carcinoma
in situ and other malignancy within 5 years prior to screening;
9. Patients with documented history of haemorrhagic diathesis, coagulopathy, or
thromboembolism;
10. Patients on concurrent treatment with exogenous reproductive hormone therapy (for
example, birth control pills, hormone replacement therapy, or megestrol acetate);
11. Patients with active systemic bacterial infection (requiring intravenous antibiotics
at time of initiating study treatment), fungal infection, or detectable viral
infection (such as known human immunodeficiency virus positivity or with known
active hepatitis B or C [for example, hepatitis B surface antigen positive];
12. Patients with serious and/or uncontrolled pre-existing medical condition(s) that, in
the judgment of the investigator, would preclude participation in this study, e.g.
interstitial lung disease (ILD), severe dyspnoea at rest requiring oxygen therapy,
severe renal impairment (i.e. estimated creatinine clearance <30 ml/min), history of
major surgical resection involving the stomach or small bowel, or preexisting
Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting
in baseline Grade 2 or higher diarrhea);
13. Patients with known allergy or hypersensitivity to any of the study drugs or any of
their excipients;
14. Patients with history of non-compliance to medical regimens;
15. Patients refusing to perform liquid and tissue biopsy;
16. Patients unwilling to or unable to comply with the protocol;
17. Patients having had major surgery within 14 days prior to screening;
18. Pregnant or lactating females prior to treatment;
19. Patients having received an experimental treatment in a clinical trial within the
last 30 days or 5 half-lives, whichever is longer, prior to initiation of study
treatment, or is currently enrolled in any other type of medical research (for
example: medical device) judged by the sponsor not to be scientifically or medically
compatible with this study;
20. Patients should be excluded if they have a known history of testing positive for
human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
(AIDS).
Gender:
Female
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
IRCCS Centro di Riferimento Oncologico (CRO)
Address:
City:
Aviano
Zip:
33081
Country:
Italy
Contact:
Last name:
Fabio Puglisi, MD
Phone:
0434659253
Email:
fabio.puglisi@cro.it
Facility:
Name:
Humanitas Istituto Clinico Catanese
Address:
City:
Catania
Zip:
95045
Country:
Italy
Contact:
Last name:
Paolo Vigneri, MD
Phone:
0957339000
Email:
vigneri.p@unict.it;vigneripaolo@gmail.com
Facility:
Name:
IRCCS Ospedale Policlinico San Martino
Address:
City:
Genova
Zip:
16132
Country:
Italy
Contact:
Last name:
Lucia Del Mastro, MD
Phone:
010.5558904 - 8908
Email:
lucia.delmastro@hsanmartino.it
Facility:
Name:
AOU Federico II
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Contact:
Last name:
Grazia Arpino, MD
Phone:
0817463772/7251
Email:
grazia.arpino@unina.it
Facility:
Name:
Istituto Nazionale Tumori "G. Pascale"
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Contact:
Last name:
Michelino De Laurentiis, MD
Phone:
08117770442
Email:
m.delaurentiis@istitutotumori.na.it;delauren@breastunit.org
Facility:
Name:
Istituto Oncologico Veneto IRCCS
Address:
City:
Padova
Zip:
35128
Country:
Italy
Contact:
Last name:
Valentina Guarneri, MD
Phone:
0498215291
Email:
valentina.guarneri@unipd.it
Facility:
Name:
Fondazione Universitaria Policlinico Gemelli IRCCS
Address:
City:
Roma
Zip:
00168
Country:
Italy
Contact:
Last name:
Alessandra Fabi, MD
Phone:
0630157337
Email:
alessandra.fabi@policlinicogemelli.it
Facility:
Name:
Ospedale Fatebenefratelli - Isola Tiberina
Address:
City:
Roma
Zip:
00186
Country:
Italy
Contact:
Last name:
Francesco Cognetti, MD
Email:
f.cognetti1@gmail.com
Start date:
April 1, 2024
Completion date:
April 1, 2027
Lead sponsor:
Agency:
Fondazione Oncotech
Agency class:
Other
Source:
Fondazione Oncotech
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06259929
