Phase Ib/III Study of Capivasertib + CDK4/6i + Fulvestrant as Treatment for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)

Phase 1

• Conditions: Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer; MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004637-20-DK
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-03-03
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

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 breast
cancer 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 completion
of 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 638
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 212

Exclusion Criteria

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-cancer
therapy, 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