Last updated 9 days ago
Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
895 patients around the world
Available in Spain, United States, Argentina
This Phase Ib/III study (CAPItello-292) aims to evaluate the efficacy, safety and the
degree of added benefit of capivasertib combined with CDK4/6i and fulvestrant in
participants with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer.
Although the dosing regimens of capivasertib + fulvestrant and of CDK4/6i + fulvestrant
are established separately, the dose and schedule for the triplet combinations
(capivasertib + CDK4/6i + fulvestrant) need to be confirmed. Therefore, the initial dose
finding Phase Ib part of the study will determine the recommended Phase III doses (RP3D)
of the triplet combinations. The Phase III part of the study will evaluate the efficacy,
safety and the degree of added benefit of the triplet combinations of capivasertib and
fulvestrant with investigator's choice of CDK4/6i (either palbociclib or ribociclib at
safe and tolerable doses, once identified) in comparison with a control arm (fulvestrant
+ investigator's choice of CDK4/6i [palbociclib or ribociclib]) in a ER+ HER2- maC high
risk population that did not receive prior endocrine therapy in the advanced setting.
AstraZeneca
7Research sites
895Patients around the world
This study is for people with
Breast Cancer
Requirements for the patient
To 99 Years
All Gender
Medical requirements
- Adult females (pre-/peri-/ and post-menopausal), and adult males.Histologically confirmed HR+/ HER2- breast cancer determined from the most recent tumour sample (primary or metastatic) per the American Society of Clinical Oncology and College of American Pathologists guideline. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.Eligible for fulvestrant therapy and at least one of the following: palbociclib, ribociclib, or abemaciclib, as per local investigator assessment. Previous tolerance to specific CDK4/6 inhibitors and dose levels required.Adequate organ and bone marrow functions.Consent to provide a mandatory FFPE tumour sample.Previous treatment with an ET (tamoxifen, AI, or oral SERD) as a single agent or in combination, with radiological evidence of breast cancer recurrence or progression while on, or within 12 months of, completing a (neo)adjuvant ET regimen.Provision of mandatory blood samples at screening for central testing using an investigational ctDNA test to be stratified based on PIK3CA/AKT1/PTEN status.Be eligible for fulvestrant and at least one out of palbociclib or ribociclib (depending on the available CDK4/6i options at time of enrolment), as per local investigator assessment.Have measurable lesion(s) according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) or, in the absence of measurable disease, lytic or mixed bone lesions that can be assessed by computed tomography (CT) or magnetic resonance imaging (MRI).
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.Radiotherapy within 2 weeks prior to study treatment initiation.Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment.Persistent toxicities (CTCAE Grade >1) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included after consultation with the AstraZeneca study physician.Spinal cord compression, brain metastases or leptomeningeal metastases unless these lesions are definitively treated and clinically stable off steroids for management of symptoms for at least 4 weeks prior to study treatment initiation.Any of the following cardiac criteria at screening.Mean resting corrected QT interval (QTcF):Participants to be treated with palbociclib: QTcF ≥ 470 ms obtained from the average of 3 consecutive ECGs.Participants to be treated with ribociclib: QTcF ≥ 450 ms obtained from the average of 3 consecutive ECGs.Participants to be treated with abemaciclib (Phase Ib only): QTcF ≥ 470 ms obtained from the average of 3 consecutive ECGs.Any clinically important abnormalities in cardiac rhythm, conduction or morphology of resting ECG.Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥ 2.Uncontrolled hypotension.Uncontrolled hypertension.Cardiac ejection fraction outside institutional range of normal or < 50%.Uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation.Any of these clinically significant abnormalities of glucose metabolism at screening.Diabetes mellitus type I or type II requiring insulin treatment.Glycated haemoglobin (HbA1c) ≥ 8.0%.Previous allogeneic bone marrow transplant or solid organ transplant.Any prior treatment with, AKT, PI3K or mTOR inhibitors.Prior treatment with CDK4/6 inhibitors in the metastatic setting.More than 1 line of chemotherapy for metastatic disease.
Sites
Instituto Médico de la Fundación Estudios Clínicos - Rosario
Recruiting
Investigaciones Clínicas Moleculares - ICM
Recruiting
Sanatorio Chivilcoy
Recruiting
Hospital General de Agudos Dra. Cecilia Grierson
Recruiting
Fundación CENIT para la Investigación en Neurociencias
Recruiting
Centro Médico Fleischer
Recruiting
Centro Médico Focus - CECIC
StudyCAPItello-292
SponsorAstraZeneca
Conditions
Breast Cancer
Requirements
To 99 YearsAll Gender
Unique study IDclinicaltrials.gov
NCT04862663
