Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)
- Conditions
- Locally Advanced (Inoperable) or Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT04862663
- Lead Sponsor
- AstraZeneca
- Brief Summary
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)
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 895
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Capivasertib Plus Palbociclib and Fulvestrant Capivasertib Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b) Capivasertib Plus Ribociclib and Fulvestrant Ribociclib Capivasertib Plus Ribociclib and Fulvestrant (Ph 1b) Capivasertib Plus Palbociclib and Fulvestrant Fulvestrant Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b) Capivasertib Plus Palbociclib and Fulvestrant Palbociclib Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b) Capivasertib Plus Abemaciclib and Fulvestrant Abemaciclib Capivasertib Plus Abemaciclib and Fulvestrant (Ph 1b) Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) Fulvestrant Fulvestrant and investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III) Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) Capivasertib Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)
- Primary Outcome Measures
Name Time Method Phase III: 1. Progression Free Survival (PFS). Up to approximately 47 months. Progression Free Survival (PFS) is defined as time from randomization until progression per RECIST v1.1. as assessed by BICR or death due to any cause in the overall population, the altered population, and the confirmed non-altered population. RECIST related endpoints such as PFS, ORR, DoR, CBR will be collected.
Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol. Within the first 28 day cycle. Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.
Phase Ib: 2. The number of participants with treatment-related adverse events. From baseline up to approximately 36 months. Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.
Phase Ib: 3. The number of participants with treatment-related serious adverse events. From baseline up to approximately 36 months. Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.
- Secondary Outcome Measures
Name Time Method Phase Ib: 4. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmin. Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 0 is 3 days and Cycle 1 is 28 days). Minimum observed plasma drug concentration.
Phase III: 2. Objective Response Rate (ORR). Up to approximately 47 months. Objective Response Rate (ORR) - the proportion of patients who have a complete or partial response, as determined by BICR per RECIST v1.1 in participants with HR+/HER2- locally advanced or metastatic breast cancer with gene alteration in PIK3CA/AKT1/PTEN - altered population, confirmed non-altered population and overall population.
Phase Ib: 3. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-24h. Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days). Partial area under the plasma concentration-time curve from zero to 24 hours post-dose.
Phase Ib: 7. PK parameters for capivasertib: Cmin. Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). Minimum observed plasma drug concentration.
Phase III: 7. Participant-reported GHS/QoL in participants Up to approximately 69 months. TTD of GHS/QoL as measured by the GHS/QoL subscale of the EORTC QLQ-C30.
Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax. Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days). Maximum observed plasma (peak) drug concentration.
Phase Ib: 2. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-72h. Cycle 0 (Cycle 0 is 3 days). Partial area under the plasma concentration-time curve from zero to 72 hours post-dose.
Phase Ib: 5. PK parameters for capivasertib: Cmax. Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). Maximum observed plasma (peak) drug concentration.
Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks. Up to approximately 36 months. Clinical Benefit Rate (CBR) 24 weeks is defined as the percentage of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by the investigator at local site for at least 23 weeks after date of first dose.
Phase III: 4. Duration of Response (DoR). Up to approximately 47 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.
Phase Ib: 10. Duration of Response (DoR). Up to approximately 36 months. Duration of Response (DoR) will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST v1.1 as assessed by the investigator at local site or death due to any cause.
Phase Ib: 6. PK parameters for capivasertib: AUC0-12h. Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). Partial area under the plasma concentration-time curve from zero to 12 hours post-dose.
Phase Ib: 11. Progression Free Survival (PFS). Up to approximately 36 months. Progression Free Survival (PFS) is defined as time from date of first dose until progression per RECIST v1.1. as assessed by the investigator at local site or death due to any cause.
Phase III: 11. The number of participants with serious adverse events. Up to approximately 69 months. Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with serious adverse events.
Phase III: 5. Clinical Benefit Rate (CBR) at 24 weeks. Up to approximately 47 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 randomisation.
Phase Ib: 8. Objective Response Rate (ORR). Up to approximately 36 months. Objective Response Rate (ORR) is defined as the proportion of patients with measurable disease at baseline who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator at local site per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Phase III: 1. Overall Survival (OS). Up to approximately 69 months. Overall survival (OS) - time from randomization until the date of death due to any cause, secondary outcome measure in participants with HR+/HER2- locally advanced or metastatic breast cancer with gene alteration in PIK3CA/AKT1/PTEN - altered population, confirmed non-altered population and overall population.
Phase III: 3. Progression Free Survival 2 (PFS2) Up to approximately 69 months. Progression Free Survival 2 (PFS2) - time from randomization to the earliest of the progression event, after first subsequent therapy or death.
Phase III: 9. Plasma concentration of capivasertib pre- and post-dose. Up to approximately 69 months. Plasma concentration of capivasertib pre-, and post-dose.
Phase III: 10. The number of participants with adverse events. Up to approximately 69 months. Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with adverse events.
Phase III: 6. Participant-reported physical functioning Up to approximately 69 months. TTD of physical functioning as measured by the physical functioning subscale of the EORTC QLQ-C30.
Phase III: 8. Participant-reported overall side effect bother in participants in the capivasertib arm relative to control arm Up to approximately 69 months. Proportion of participants experiencing different levels of overall treatment tolerability as measured by the Patient Global Impression-Treatment Tolerability (PGI-TT).
Trial Locations
- Locations (1)
Research Site
🇻🇳Vinh, Vietnam