This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292) (CAPItello-292)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04862663
Recruitment Status : Recruiting
First Posted : April 28, 2021
Last Update Posted : April 16, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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)

Condition or disease Intervention/treatment Phase
Locally Advanced (Inoperable) or Metastatic Breast Cancer Drug: Capivasertib Drug: Fulvestrant Drug: Palbociclib Drug: Ribociclib Drug: Abemaciclib Phase 3

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.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 895 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Phase Ib: Open, Parallel groups allowed, recruiting up to approx. 222 participants.

Phase III: open-label, randomised, recruiting approx. 628 participants.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : May 10, 2021
Estimated Primary Completion Date : November 1, 2027
Estimated Study Completion Date : August 14, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Capivasertib Plus Palbociclib and Fulvestrant
Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b)
 Drug: Capivasertib
Phase Ib: Capivasertib 320 mg/ 400 mg administered PO BD 4 days on /3 days off per week for 4 weeks (28 days cycle) Phase III: : Capivasertib, administered PO BD 4 days on / 3 days off per week for 4 weeks (28 days cycle) at the dose confirmed in the phase Ib portion

Drug: Fulvestrant
Phase Ib and Phase III: 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter

Drug: Palbociclib
Phase Ib: 100 mg/ 125 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose of 125 mg.
Experimental: Capivasertib Plus Ribociclib and Fulvestrant
Capivasertib Plus Ribociclib and Fulvestrant (Ph 1b)
 Drug: Ribociclib
Phase Ib: 200 mg/ 400 mg/ 600 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose confirmed in the phase 1b portion.
Experimental: Capivasertib Plus Abemaciclib and Fulvestrant
Capivasertib Plus Abemaciclib and Fulvestrant (Ph 1b)
 Drug: Abemaciclib
Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle
Experimental: Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)
Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)
 Drug: Capivasertib
Phase Ib: Capivasertib 320 mg/ 400 mg administered PO BD 4 days on /3 days off per week for 4 weeks (28 days cycle) Phase III: : Capivasertib, administered PO BD 4 days on / 3 days off per week for 4 weeks (28 days cycle) at the dose confirmed in the phase Ib portion
Active Comparator: Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)
Fulvestrant and investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)
 Drug: Fulvestrant
Phase Ib and Phase III: 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol. [ Time Frame: 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.

  2. Phase Ib: 2. The number of participants with treatment-related adverse events. [ Time Frame: 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.

  3. Phase Ib: 3. The number of participants with treatment-related serious adverse events. [ Time Frame: 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.

  4. Phase III: 1. Progression Free Survival (PFS). [ Time Frame: Up to approximately 37 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. RECIST related endpoints such as PFS, ORR, DoR, CBR will be collected


Secondary Outcome Measures :
  1. Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax. [ Time Frame: 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.

  2. Phase Ib: 2. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-72h. [ Time Frame: Cycle 0 (Cycle 0 is 3 days). ]
    Partial area under the plasma concentration-time curve from zero to 72 hours post-dose.

  3. Phase Ib: 3. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-24h. [ Time Frame: 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.

  4. Phase Ib: 4. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmin. [ Time Frame: 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.

  5. Phase Ib: 5. PK parameters for capivasertib: Cmax. [ Time Frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
    Maximum observed plasma (peak) drug concentration.

  6. Phase Ib: 6. PK parameters for capivasertib: AUC0-12h. [ Time Frame: 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.

  7. Phase Ib: 7. PK parameters for capivasertib: Cmin. [ Time Frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
    Minimum observed plasma drug concentration.

  8. Phase Ib: 8. Objective Response Rate (ORR). [ Time Frame: 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).

  9. Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks. [ Time Frame: 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.

  10. Phase Ib: 10. Duration of Response (DoR). [ Time Frame: 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.

  11. Phase Ib: 11. Progression Free Survival (PFS). [ Time Frame: 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.

  12. Phase III: 1. 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.

  13. Phase III: 2. 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.

  14. Phase III: 3. Progression Free Survival 2 (PFS2). [ Time Frame: Up to approximately 64 months. ]
    Progression Free Survival (PFS2) - time from randomisation to the earliest of the progression event, after first subsequent therapy or death.

  15. Phase III: 4. 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.

  16. Phase III: 5. 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.

  17. Phase III: 6. 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 randomisation.

  18. Phase III: 7. 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.

  19. Phase III: 8. participant-reported GHS/QoL in participants [ Time Frame: Up to approximately 64 months. ]
    TTD of GHS/QoL as measured by the GHS/QoL subscale of the EORTC QLQ-C30.

  20. Phase III: 9. 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).

  21. Phase III: 10. Plasma concentration of capivasertib pre- and post-dose. [ Time Frame: Up to approximately 64 months. ]
    Plasma concentration of capivasertib pre-, and post-dose.

  22. Phase III: 11. The number of participants with adverse events. [ Time Frame: Up to approximately 64 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.

  23. Phase III: 12. The number of participants with serious adverse events. [ Time Frame: Up to approximately 64 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key inclusion criteria for both phases:

  1. Adult females (pre-/peri-/ and 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. 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.
  4. Adequate organ and bone marrow functions.
  5. Consent to provide a mandatory FFPE tumour sample.

Inclusion criteria only for phase III:

1. Previous treatment with an ET (tamoxifen, AI, or oral SERD) as a single agent or in combination, with:

a. radiological evidence of breast cancer recurrence or progression while on, or within 12 months of, completing a (neo)adjuvant ET regimen

Key exclusion criteria for both phases:

  1. 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.
  2. Radiotherapy within 2 weeks prior to study treatment initiation.
  3. Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment.
  4. 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.
  5. 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.

  6. 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)

  7. uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation

  8. Any of these clinically significant abnormalities of glucose metabolism at screening:

    1. . diabetes mellitus type I or type II requiring insulin treatment
    2. . HbA1c ≥ 8.0% (63.9 mmol/mol)
  9. Previous allogeneic bone marrow transplant or solid organ transplant.

Key exclusion criteria for the phase III only:

  1. Any prior treatment with, AKT, PI3K or mTOR inhibitors.
  2. 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).
  3. More than 1 line of chemotherapy for metastatic disease
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04862663


Contacts
Layout table for location contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AZ Breast Cancer Study Navigators +1-877-400-4656 AstraZeneca@CareboxHealth.com

Locations
Show Show 228 study locations
Sponsors and Collaborators
AstraZeneca
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04862663    
Other Study ID Numbers: D361DC00001
2020-004637-20 ( EudraCT Number )
First Posted: April 28, 2021    Key Record Dates
Last Update Posted: April 16, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Locally advanced (inoperable) or Metastatic Breast Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Palbociclib
Antineoplastic Agents, Hormonal
Antineoplastic Agents
 Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action