CTRI/2024/01/061642招募中3 期
A Phase Ib/III, Open-label, Randomised Study of Capivasertib plus CDK4/6 Inhibitors and Fulvestrant versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 628
- 试验地点
- 12
- 主要终点
- Progression Free Survival (PFS). [ Time Frame: Up to approximately 37 months. ]
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion criteria:
- •Adult females (pre-/peri-/ and post-menopausal), and adult males.
- •Metastatic or locally advanced disease with radiologic or clinical evidence of recurrence or progression or intolerance to last/current treatment
- •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.
- •Adequate organ and bone marrow functions.
- •ECOG performance status 0 to 1
- •Consent to provide a mandatory FFPE tumour sample.
- •Eligible for fulvestrant therapy and at least one of the following: palbociclib or ribociclib, as per local investigator assessment.
- •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.
排除标准
- •Exclusion Criteria:
- •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 (eg, hearing loss or peripheral sensory neuropathy) after consultation with the AstraZeneca study physician.
- •Spinal cord compression, brain metastases or leptomeningeal metastases unless these lesions are definitively treated (eg.
- •radiotherapy, surgery) 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: (a).
- •Mean resting corrected QT interval (QTcF): (i) Participants to be treated with palbociclib: QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate) ECGs (ii) Participants to be treated with ribociclib: QTcF ≥ 450 ms obtained from the average of 3 consecutive (triplicate) ECGs (iii) Participants to be treated with abemaciclib (Phase Ib only): QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate) ECGs (b).
- •Any clinically important abnormalities in cardiac rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third-degree heart 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, unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥ 2 (e).
- •Uncontrolled hypotension (f) uncontrolled hypertension (g).
- •Cardiac ejection fraction outside institutional range of normal or < 50% (whichever is higher)
- •uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation
- •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)
- •Previous allogeneic bone marrow transplant or solid organ transplant.
- •Prior treatment with CDK4/6 inhibitors in the metastatic setting (prior CDK4/6 inhibitors permitted in the adjuvant setting provided there was a CDK4/6i treatment free interval of at least 12 months).
- •More than 1 line of chemotherapy for metastatic disease.
结局指标
主要结局
Progression Free Survival (PFS). [ Time Frame: Up to approximately 37 months. ]
时间窗: Progression Free Survival (PFS). [ Time Frame: Up to approximately 37 months. ]
次要结局
- Overall Survival (OS). [Time Frame: Up to approximately 64 months.](Overall Survival (OS) - time from randomisation until the date of death due to any cause.)
- Progression Free Survival (PFS) in PIK3CA/ AKT1/ PTEN-altered population. [Time Frame: Up to approximately 37 months.](Progression Free Survival (PFS) - time from randomisation until progression per RECIST v 1.1 as assessed by BICR or death due to any cause)
- Progression Free Survival 2 (PFS2). [Time Frame: Up to approximately 64 months.](Progression Free Survival (PFS2) - time from randomization to the earliest of the progression event, after first subsequent therapy or death.)
- Objective Response Rate (ORR). [Time Frame: Up to approximately 37 months.](Objective Response Rate (ORR) - the proportion of patients who have a complete or partial response), as determined by BICR per RECIST v1.1.)
- Duration of Response (DoR). [Time Frame: Up to approximately 37 months.](Duration of Response (DoR) - the time from the date of first documented response until the date of progression per RECIST v1.1 as assessed by BICR, or death due to any cause.)
- Clinical Benefit Rate (CBR) at 24 weeks. [Time Frame: Up to approximately 37 months.](Clinical Benefit Rate (CBR) at 24 weeks-the % of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by BICR for at least 23 weeks after randomization.)
- Participant- reported physical functioning. [Time Frame: Up to approximately 64 months.](TTD of physical functioning as measured by the physical functioning subscale of the EORTC QLQ-C30.)
- TTD of physical functioning as measured by the physical functioning subscale of the EORTC QLQ-C30.(TTD of GHS/QoL as measured by the GHS/QoL subscale of the EORTC QLQ-C30.)
- Participant-reported overall side effect bother in participants in the capivasertib arm relative to control arm. [Time Frame: Up to approximately 64 months.](Proportion of participants experiencing different levels of overall treatment tolerability as measured by the Patient Global Impression-Treatment Tolerability (PGI-TT).)
- Plasma concentration of capivasertib pre- and post-dose. [Time Frame: Up to approximately 64 months.](Plasma concentration of capivasertib pre, and post-dose.)
- The number of participants with adverse events. [Time Frame: Up to approximately 64 months.](Data will include clinical observations, ECG parameters, clinical chemistry hematology glucose metabolism parameters and vital signs assessed as the number of participants with adverse events.)
- The number of participants with serious adverse events. [Time Frame: Up to approximately 64 months.](Data will include clinical observations, ECG parameters, clinical chemistry hematology glucose metabolism parameters and vital signs assessed as the number of participants with serious adverse events.)
研究者
Mr Sandeep AV
AstraZeneca Pharma India Ltd
研究点 (12)
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