Phase Ib/III Study of Capivasertib + CDK4/6i + Fulvestrant as Treatment for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
- Conditions
- Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast CancerMedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004637-20-PL
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 850
Key inclusion criteria for both phases: 1. Adult females (pre- and/or post-menopausal), and adult males.2. 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 breastcancer must express ER with or without co-expression of progesterone receptor. 3. Adequate organ and bone marrow functions.4. Consent to provide a mandatory FFPE tumour sample.
Inclusion criteria only for phase I: 1. Eligible for fulvestrant therapy and at least one of the following: palbociclib, ribociclib, or abemaciclib, as per local investigator assessment.
Inclusion criteria only for phase III: 1. Radiologic measurable relapse during neoadjuvant / adjuvant endocrine therapy or evidence of relapse within 12 months of completionof adjuvant therapy or disease progression during the initial 12 months of 1L endocrine therapy in locally advanced unresectable or metastatic breast cancer.2. Received up to a maximum of 1 lines of prior chemotherapy in the advanced/metastatic setting without progression during the chemotherapy planned course.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 525
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 175
Key exclusion criteria for both phases:1. History of another primary malignancy except for malignancy treated with curative intent with no known active disease = 5 years before the first dose of study intervention and of low potential risk for recurrence. 2. Radiotherapy within 2 weeks prior to study treatment initiation. 3. Major surgical procedure within 4 weeks of the first dose of study treatment. 4. Persistent toxicities (>CTCAE Grade 1) caused by previous anti-cancertherapy, excluding alopecia. Participants with irreversible toxicity expected to be exacerbated by study intervention may be included (eg, hearing loss or peripheral sensory neuropathy) after consultation with the AstraZeneca study physician. 5. Spinal cord compression, brain metastases or leptomeningeal metastases unless these lesions were treated and confirmed stable, asymptomatic and not requiring steroids for the management of the symptoms within 4 weeks prior to study treatment initiation. 6. Any of the following cardiac criteria at screening: (a). Mean resting corrected QT interval (QTcF): Abemaciclib and palbociclib arms: QTcF = 470 msec obtained from the average of 3 consecutive (triplicate) ECGs Ribociclib arm: QTcF = 450 msec obtained from the average of 3 consecutive (triplicate) ECGs(b). Any clinically important abnormalities in rhythm, conduction or morphology of ECG (eg, complete left bundle branch block, second or third-degree AV block) (c). Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (d). Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) grade = 2 (e). Uncontrolled hypotension (f). Cardiac ejection fraction outside institutional range of normal or < 50% (whichever is higher) unless the condition is considered stable and not clinically significant by the investigator. 7. Any of these clinically significant abnormalities of glucose metabolism at screening: (a). diabetes mellitus type I or type II requiring insulin treatment (b). HbA1c = 8.0% (63.9 mmol/mol) 8. Previous allogeneic bone marrow transplant or solid organ transplant. 9. For the phase III: Prior treatment with CDK4/6 inhibitors (in the metastatic setting), a SERD, allosteric mTOR inhibitors, PI3K inhibitors or AKT inhibitors in the metastatic setting.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method