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CTRI Number  CTRI/2024/01/061642 [Registered on: 19/01/2024] Trial Registered Prospectively
Last Modified On: 28/05/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Phase Ib/III Study of Capivasertib + CDK4/6 Inhibitors + Fulvestrant as Treatment for Advanced/Metastatic HR+/HER2-Breast Cancer 
Scientific Title of Study   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) 
Trial Acronym  CAPItello-292 
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
D361DC00001 V7.0 Dated 20-Mar-2025  Protocol Number 
NCT04862663  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Mr Sandeep AV 
Designation  Senior Director, Oncology Country Head, Oncology Site Management and Monitoring India 
Affiliation  AstraZeneca Pharma India Ltd 
Address  AstraZeneca Pharma India Ltd. Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, Bangalore – 560045

Bangalore
KARNATAKA
560045
India 
Phone  9845079472  
Fax  080-67748857  
Email  Sandeep.AV@astrazeneca.com  
 
Details of Contact Person
Scientific Query  
Name  Mr Sandeep AV 
Designation  Senior Director, Oncology Country Head, Oncology Site Management and Monitoring India 
Affiliation  AstraZeneca Pharma India Ltd 
Address  AstraZeneca Pharma India Ltd. Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, Bangalore – 560045


KARNATAKA
560045
India 
Phone  9845079472  
Fax  080-67748857  
Email  Sandeep.AV@astrazeneca.com  
 
Details of Contact Person
Public Query  
Name  Mr Sandeep AV 
Designation  Senior Director, Oncology Country Head, Oncology Site Management and Monitoring India 
Affiliation  AstraZeneca Pharma India Ltd 
Address  AstraZeneca Pharma India Ltd. Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, Bangalore – 560045


KARNATAKA
560045
India 
Phone  9845079472  
Fax  080-67748857  
Email  Sandeep.AV@astrazeneca.com  
 
Source of Monetary or Material Support  
151 85 Sodertalje, Sweden 
AstraZeneca AB 
 
Primary Sponsor  
Name  AstraZeneca AB 
Address  151 85 Södertälje Sweden a member of the AstraZeneca group 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
AstraZeneca Pharma India Ltd  Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, Bangalore – 560045, India  
 
Countries of Recruitment     Argentina
Australia
Belgium
Brazil
Canada
China
Denmark
France
Germany
India
Italy
Japan
Malaysia
Poland
Republic of Korea
Spain
Sweden
Taiwan
Thailand
Turkey
United Kingdom
United States of America
Viet Nam  
Sites of Study
Modification(s)  
No of Sites = 12  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Parveen Jain  Aakash Healthcare Super Speciality Hospital  Department of Oncology Hospital Plot, Road No. 201, Dwarka Sector-3, New Delhi, Delhi 110075, India
New Delhi
DELHI 		 9811775324

drparveen1010@gmail.com 
Dr Aseem Kumar Samar  Bhagwan Mahaveer Cancer Hospital & Research Centre  Department of Oncology Jawahar Lal Nehru Marg, Jaipur - 302 017, Rajasthan, India
Jaipur
RAJASTHAN 		 9004399604

aseemtmh@gmail.com 
Dr Abhilash G H  Bharath Hospital and Institute of Oncology  Department of Oncology No. 438, 1st Stage, Outer Ring Road, Hebbal Industrial Area, Lakshmikanth Nagar Mysuru (Mysore) - 570 017, Karnataka, India
Mysore
KARNATAKA 		 9812316441

drabhilashgh@gmail.com 
Dr Ajay Gupta  Indraprastha Apollo Hospital  Department of Oncology Sarita Vihar, Mathura Road, New Delhi - 110076, India
New Delhi
DELHI 		 7838013018

oncol@rediffmail.com 
Dr Biswajit Dubashi  Jawaharlal Institute of Post-graduate Medical Education & Research  Department of Oncology Dhanvantri Nagar, Gorimedu, Puducherry - 605 006, India
Pondicherry
PONDICHERRY 		 8056338405

drbiswajitdm@gmail.com 
Dr Santhosh Vandanasetti  Kailash Cancer Hospital & Research Centre  Department of Oncology Muniseva Ashram, Goraj, Waghodiya, Vadodara - 391 760, Gujarat, India
Vadodara
GUJARAT 		 9427423693

vandanasetti.santhosh@greenashram.org 
Dr Mukesh Bang  KIMS-Kingsway Hospitals  Department of Oncology SPANV Medisearch Lifesciences Private Limited 44, Parwana Bhawan, Kingsway, Nagpur - 440 001, Maharashtra, India
Nagpur
MAHARASHTRA 		 9422869635

drmukeshbang31@gmail.com 
Dr Akhil Kapoor  Mahamana Pandit Madan Mohan Malviya Cancer Center  Department of Oncology Sundar Bagiya, Near Nariya Gate, Banaras Hindu University Campus, Varanasi - 221 005, Uttar Pradesh, India
Varanasi
UTTAR PRADESH 		 7597364554

kapoorakhil1987@gmail.com 
Dr Sachin Gupta  Max Super Speciality Hospital (A Unit of Hometrail Buildtech Pvt Ltd)  Department of Oncology Near Civil Hospital, Phase-6, Mohali, Punjab-160055, India
Rupnagar
PUNJAB 		 8968839911

sachin.gupta@maxhealthcare.com 
Dr Prashant Kumbhaj  Sri Ram Cancer & Super Speciality Centre  Department of Oncology RIICO Institutional Area, Tonk Road, Sitapur, Near Jaipur Gate, Sanganer, Jaipur - 302 029, Rajasthan, India
Jaipur
RAJASTHAN 		 7869409560

drprashantkumbhaj@yahoo.com 
Dr Vijai Simha  Sri Shankara Cancer Hospital and Research Centre  Department of Oncology 1st Cross, Shankarapuram, Basavanagudi, Bangalore - 560 004, Karnataka, India
Bangalore
KARNATAKA 		 9914179639

vijaiaditya1985@gmail.com 
Dr Joydeep Ghosh  Tata Medical Center  Department of Oncology 14 MAR (EW), Newtown, Kolkata - 700 160, West Bengal, India
Kolkata
WEST BENGAL 		 9167874217

dr.joydeep.ghosh@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 12  
Name of Committee  Approval Status 
Aakash Healthcare Institutional Ethics Committee  Approved 
IEC Intervention Studies, JIPMER  Submittted/Under Review 
IEC, MPMMCC and HBCH Varanasi Mahamana Pandit Madan Mohan Malviya Cancer Centre  Approved 
IEC-KCHRC Kailash Cancer Hospital And Research Centre  Approved 
Institutional Ethics Committee Bhagwan Mahaveer Cancer Hospital And Research Centre  Approved 
Institutional Ethics Committee Bharath Hospital and Institute of Oncology  Approved 
Institutional Ethics Committee Mahatma Gandhi Medical College & Hospital  Approved 
Institutional Ethics Committee – Clinical Studies Indraprastha Apollo Hospitals  Approved 
Institutional Ethics Committee(IEC) Max Super Speciality Hospital  Approved 
Institutional Review Board, Tata Medical Center  Submittted/Under Review 
Kingsway Hospitals Ethics Committee, Kingsway Hospitals  Approved 
Sri Sankara Cancer Hospital and Research Centre  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  , (1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Capivasertib + fulvestrant + Investigators choice of CDK4/6i (palbociclib or ribociclib)  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. Fulvestrant 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. Palbociclib administered once daily for 21 days of 28-day cycle, at the dose of 125 mg. Ribociclib administered once daily for 21 days of 28-day cycle, at the dose confirmed in the phase 1b portion. 
Comparator Agent  Fulvestrant + Investigators choice of CDK4/6i (palbociclib or ribociclib)  Fulvestrant 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. Palbociclib administered once daily for 21 days of 28-day cycle, at the dose of 125 mg. Ribociclib administered once daily for 21 days of 28-day cycle, at the dose confirmed in the phase 1b portion. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Inclusion criteria:
1. Adult females (pre-/peri-/ and post-menopausal), and adult males.
2. Metastatic or locally advanced disease with radiologic or clinical evidence of recurrence or progression or intolerance to last/current treatment
3. 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.
4. Adequate organ and bone marrow functions.
5. ECOG performance status 0 to 1
6. Consent to provide a mandatory FFPE tumour sample.
7. Eligible for fulvestrant therapy and at least one of the following: palbociclib or ribociclib, as per local investigator assessment.
8. 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 
 
ExclusionCriteria 
Details  Exclusion Criteria:
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:
a. diabetes mellitus type I or type II requiring insulin treatment
b. HbA1c ≥ 8.0% (63.9 mmol/mol)
9. Previous allogeneic bone marrow transplant or solid organ transplant.
10. Any prior treatment with, AKT, PI3K or mTOR inhibitors.
11. 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).
12. More than 1 line of chemotherapy for metastatic disease. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Progression Free Survival (PFS). [ Time Frame: Up to approximately 37 months. ]  Progression Free Survival (PFS). [ Time Frame: Up to approximately 37 months. ] 
 
Secondary Outcome  
Outcome  TimePoints 
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. 
 
Target Sample Size   Total Sample Size="628"
Sample Size from India="50" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)
Modification(s)  		 14/03/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  01/11/2023 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="28"
Months="11"
Days="30" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   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. 
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