FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2019/08/020833 [Registered on: 21/08/2019] Trial Registered Prospectively
Last Modified On: 01/06/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   Capivasertib plus Paclitaxel as First line Treatment for Locally Advanced (Inoperable) or Metastatic Triple Negative Breast Cancer (CAPItello290) 
Scientific Title of Study   A Phase III Double blind Randomised Study Assessing the Efficacy and Safety of Capivasertib plus Paclitaxel Versus Placebo plus Paclitaxel as First line Treatment for Patients with Histologically Confirmed, Locally Advanced (Inoperable) or Metastatic Triple-Negative Breast Cancer (TNBC)  
Trial Acronym   
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
D3614C00001_Protocol Version 3.0 dated 12 Nov 2019  Protocol Number 
NCT03997123  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query
 
Name  Tapankumar M Shah 
Designation  Country Director, Clinical Operations 
Affiliation  AstraZeneca Pharma India Ltd 
Address  Clinical Operation Dept. AstraZeneca Pharma India Ltd, Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road,

Bangalore
KARNATAKA
560045
India 
Phone  919535104975  
Fax  918067748857  
Email  tapankumar.shah@astrazeneca.com  
 
Details of Contact Person
Public Query
 
Name  Tapankumar M Shah 
Designation  Country Director, Clinical Operations 
Affiliation  AstraZeneca Pharma India Ltd 
Address  Clinical Operation Dept., AstraZeneca Pharma India Ltd, Block N1, 12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road

Bangalore
KARNATAKA
560045
India 
Phone  919535104975  
Fax  918067748857  
Email  tapankumar.shah@astrazeneca.com  
 
Source of Monetary or Material Support  
AstraZeneca AB, 151 85 Sodertalje, Sweden  
 
Primary Sponsor  
Name  AstraZeneca AB  
Address  151 85 Sodertalje, Sweden 
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  
 
Countries of Recruitment     Argentina
Brazil
Canada
Czech Republic
France
India
Japan
Philippines
Poland
Republic of Korea
Russian Federation
Saudi Arabia
Spain
Sweden
Taiwan
Turkey
United Kingdom
United States of America  
Sites of Study
Modification(s)  
No of Sites = 13  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr P N Mohapatra   Apollo Gleneagles Hospitals, Kolkata   Dept of Medical Oncology 58-Canal Circular Road PIN 700054
Kolkata
WEST BENGAL 
919674311610

prabrajya.mohapatra@rediffmail.com 
Dr Hari Goyal  Artemis Hospital  Dept of Medical Oncology Senior Consultant and Unit Head Medical Oncologist Sector 51 Gurgaon 122001
Gurgaon
HARYANA 
01246767999
01246767701
Harig@artemishospitals.com 
Dr Prasad Narayanan  CYTECARE HOSPITALS PVT LTD  Dept of Medical Oncology, Senior Consultant, Venkatala, Near Bagalur Cross, Yelahanka
Bangalore
KARNATAKA 
8884122456

prasad.narayanan@cytecare.com 
Dr Chetan Deshmukh   Deenanath Mangeshkar Hospital and Research center  Erandwane PIN 411004
Pune
MAHARASHTRA 
9850811449

drchetandeshmukh@gmail.com 
Dr Ravi Kumar Saxena  Gleneagles Global Clinical Research Services Pvt Ltd  Dept of Medical Oncology, Lakdi- Ka-Pul-500004
Hyderabad
TELANGANA 
9949385000

ravikumar1960@hotmail.com 
Dr Shruti Kate  HCG Manavata Cancer Centre  Dept of Medical Oncology, Senior Consultant Medical Oncologist, HCG Manavata Cancer Centre, Behind Shivang Auto, Mumbai Naka, Nasik PIN 422002
Nashik
MAHARASHTRA 
02536661111

drshruti@mcrinasik.com 
Dr P K Das  Indraprastha Apollo Hospitals Sarita Vihar  Dept of Medical Oncology Delhi-Mathura Road, New Delhi PIN 1100076
New Delhi
DELHI 
9810444600

drpratapdas@gmail.co 
Dr Vaibhav Choudhary  Meditrina Institute of Medical Sciences  Dept of Medical Oncology, Consultant Medical Oncologist, 278.Central Bazar Road, Ramdaspeth, Nagpur PIN 440010
Nagpur
MAHARASHTRA 
9833621049

dr.vaibhav155@gmail.com 
Dr Kirushna Kumar KS  Meenakshi Mission Hospital & Research Institute  Dept. of Medical Oncology Meenakshi Mission Hospital and Research Centre, Lake Area, Melur Road PIN-625107
Madurai
TAMIL NADU 
9380417299

drkskk@yahoo.com 
Dr Ullas Batra  Rajiv Gandhi Cancer Institute and Research Centre  Dept of Medical Oncology, Senior Consultant and Head of Thoracic Medical Oncology, Sector 5, Rohini PIN 110085
North
DELHI 
9711080001

ullasbatra@gmail.com 
Dr Joydeep Ghosh   Tata Medical Center  Dept of Medical Oncology, Consultant Medical Oncologist 14 Major Arterial Road EW, Newtown, Rajarhat PIN 700160
Kolkata
WEST BENGAL 
03366057000
03366057635
joydeep.ghosh@tmckolkata.com 
Dr Sudeep Surender Gupta   Tata Memorial Centre   Dept. of Medical Oncology Homi Bhabha Block, Dr Ernest Borges Marg, Parel PIN 400012
Mumbai
MAHARASHTRA 
02224177201
02224165449
sudeepgupta@tatahospital.net 
Dr Niti Raizada  Vikram Hospital Bengaluru Pvt. Ltd.  Senior Consultant, Medical Oncologist and Hemato-Oncologist, Dept. of Medical Oncology, #71/1, Millers Road, Opp. to St. Annes College PIN - 560052
Bangalore
KARNATAKA 
9901205647

nitiraizada@icloud.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 13  
Name of Committee  Approval Status 
Artemis Health Sciences Institutional Ethics Committee  Approved 
Cytecare Institutional Ethics Committee  Approved 
Institutional Ethics Committee Gleneagles Global Hospitals, Hyderabad  Approved 
Institutional Ethics Committee, Apollo Gleneagles Hospitals, Kolkata  Submittted/Under Review 
Institutional Ethics Committee, Deenanath Mangeshkar Hospital & Research Center   Approved 
Institutional Ethics Committee-Clinical Studies, Indraprastha Apollo Hospitals Delhi  Approved 
Institutional Review Board Rajiv Gandhi Cancer Institute and Research Centre  Approved 
Institutional Review Board Tata Medical Center, Kolkata  Approved 
Manavata Clinical Research Institute Ethics Committee  Approved 
Meditrina Institute Ethics Committee  Approved 
Meenakshi Mission Hospital and Research Centre (MMHRC) INSTITUTIONAL ETHICS COMMITTEE   Approved 
TATA Memorial Hospital Institutional Ethics Committee  Submittted/Under Review 
Vikram Hospital (Bangaluru) Pvt. Ltd. Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  C509||Malignant neoplasm of breast of unspecified site,  
 
Intervention / Comparator Agent
Modification(s)  
Type  Name  Details 
Intervention  Capivasertib plus Paclitaxel   Capivasertib: Dose and frequency of dosing - will be given as an intermittent weekly dosing schedule. on weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle. Route of administration - Oral Duration of therapy - Study treatment will be continued until disease progression unless there is evidence of unacceptable toxicity, or if the patient requests to stop the study treatment. Paclitaxel: Dose and frequency of dosing- Patients will receive 3 consecutive weekly infusions followed by 1 week off-treatment within each 28-day treatment cycle. Route of administration - Intravenous infusion Duration of therapy - Paclitaxel treatment will be continued for at least 6 cycles unless the patient experiences unacceptable toxicity that is attributed directly to treatment with paclitaxel.  
Comparator Agent  Placebo plus Paclitaxel   Placebo: Dose and frequency of dosing - will be given on an intermittent weekly dosing schedule on weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle. Route of administration - Oral Duration of therapy - Study treatment will be continued until disease progression unless there is evidence of unacceptable toxicity, or if the patient requests to stop the study treatment. Paclitaxel: Dose and frequency of dosing- Patients will receive 3 consecutive weekly infusions followed by 1 week off-treatment within each 28-day treatment cycle Route of administration - Intravenous infusion Duration of therapy - Paclitaxel treatment will be continued for at least 6 cycles unless the patient experiences unacceptable toxicity that is attributed directly to treatment with paclitaxel.  
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Patients are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply:

Informed Consent:
1 Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the clinical study protocol (CSP)
2 Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
3 For inclusion in the optional exploratory genetic and/or biomarker research, provision of signed and dated written genetic and/or biomarker informed consents, respectively, prior to collection of sample

If a patient declines to participate in the optional exploratory genetic research and/or the optional biomarker research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.

Age:
4 Patients must be aged ≥18 years at the time of signing the ICF

Type of patient and disease characteristics:
5 Histologically confirmed breast cancer
6 Metastatic or locally advanced disease; locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
7 Triple-negative disease, determined from the most recent tumour sample taken for diagnostic purposes (accompanied by an associated pathology report), defined as:
i) Negative for ER with <1% of tumour cells positive for ER on immunohistochemistry (IHC) or IHC score (Allred) of ≤2,
ii) Negative for PR with <1% of tumour cells positive for PR on IHC or IHC score (Allred) of ≤2 or PR unknown, and
iii) Negative for HER2 with 0, 1+ intensity on IHC or 2+ intensity on IHC and no evidence of amplification on in situ hybridisation as per the American Society of Clinical Oncology College of American Pathologists. HER2 guideline recommendations
8 Eligible for taxane monotherapy as per local investigator assessment
9 Patients must have:
i) At least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computer tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements, or
ii) Lytic or mixed (lytic + sclerotic) bone lesions that can be assessed by CT or MRI in the absence of measurable disease as defined above; patients with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are not eligible.
10 Consent to submit and provision of a mandatory FFPE sample for central testing. A FFPE tissue block from the most recently collected pre-randomisation tumour sample (primary or recurrent cancer) is preferred. If it is not possible to provide a tissue block, at least 20 freshly-cut unstained serial tumour slides are to be provided. Sample requirements are further described in the Pathology and Genomic Testing Manual.
11 Patients must be able to swallow and retain oral medication
12 ECOG/WHO performance status 0-1 with no deterioration over the previous 2 weeks and life expectancy of ≥12 weeks

Reproduction:
13 Female patients of childbearing potential should be willing to use 2 forms of highly reliable methods of contraception from the time of screening until 4 weeks after discontinuing capivasertib/placebo or until 6 months after discontinuing paclitaxel, whichever occurs later
OR
Patients must have evidence of an inability to bear children by fulfilling 1 of the following criteria at screening:
i) Post-menopausal – defined as aged >50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
ii) Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but not tubal ligation
14 Female patients must not be breast-feeding and must have a negative pregnancy test prior to start of dosing
15 Male patients should use barrier contraception (ie, condoms) from the time of screening until 16 weeks after discontinuation of capivasertib/placebo or 6 months after discontinuing paclitaxel, whichever occurs later. It is not known whether the preclinical changes seen in the male animal reproductive organs, after treatment with capivasertib, will be fully reversible or will permanently affect the ability to produce healthy sperm following treatment. Therefore, if male patients may wish to father children in the future they should be advised to arrange for freezing of sperm samples prior to the start of study treatment
 
 
ExclusionCriteria 
Details  Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

Medical conditions:
1 Malignancies other than breast cancer within 5 years prior to treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
2 Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment (capivasertib/placebo)
3 Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
4 Pre-existing sensory or motor polyneuropathy ≥grade 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5)
5 With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
6 Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment
7 Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
8 Any of the following cardiac criteria at screening:
i) Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive ECGs
ii) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block)
iii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, potential for Torsades de Pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
iv) 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
v) Uncontrolled hypotension – SBP <90 mmHg and/or DBP <50 mmHg
vi) Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive).
9 Clinically significant abnormalities of glucose metabolism as defined by any of the following at screening:
i) Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment
ii) HbA1c ≥8.0% (63.9 mmol/mol)
10 Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values at screening:
i) Absolute neutrophil count <1.5 × 109/L
ii) Platelet count <100 × 109/L
iii) Haemoglobin <9 g/dL (<5.59 mmol/L). [Note: any blood transfusion must be >14 days prior to the determination of a haemoglobin ≥9 g/dL (≥5.59 mmol/L)]
iv) Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) >2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or >5 × ULN in the presence of liver metastases. Elevated alkaline phosphatase (ALP) is not exclusionary if due to the presence of bone metastasis and liver function is otherwise considered adequate in the investigator’s judgement
v) Total bilirubin >1.5 × ULN (patients with confirmed Gilbert’s syndrome may be included in the study)
vi) Creatinine >1.5 × ULN concurrent with creatinine clearance <50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 × ULN
11 As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required
12 Refractory nausea and vomiting, malabsorption syndrome, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib
13 Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent
14 Evidence of dementia, altered mental status or any psychiatric condition that would prohibit understanding or rendering of informed consent
15 Previous allogeneic bone marrow transplant or solid organ transplant
16 Known immunodeficiency syndrome
Prior therapy:
17 Prior treatment with any of the following:
AKT, PI3K, and/or mTOR inhibitors
 Any prior systemic therapy for inoperable locally advanced or metastatic disease
i) Capivasertib in the present study (ie, any dosing with capivasertib due to previous participation in this study)
ii) Chemotherapy in the (neo)adjuvant setting within 12 months from the end of chemotherapy to inclusion into this study
iii) Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
iv) Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment
v) Any other chemotherapy, immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents within 3 weeks of the first dose of study treatment. A longer washout may be required for drugs with a long half-life (eg, biologics) as agreed by the sponsor
vi) Potent inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John’s wort), or sensitive substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week prior to the first dose of study treatment. For details, see Appendix D
Prior/concurrent clinical study experience
18 Previous randomisation in this study
19 Participation in another clinical study with an investigational medicinal product (IMP) administered in the last 30 days or 5 half-lives, whichever is longer
20 History of hypersensitivity to active or inactive excipients of capivasertib or drugs with a similar chemical structure or class to capivasertib

Other exclusions:
21 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
22 Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
23 History of hypersensitivity to paclitaxel or to any of the excipients
24 Currently pregnant (confirmed with positive pregnancy test) or breast-feeding
 
 
Method of Generating Random Sequence   Stratified block randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
Progression-Free Survival (PFS): Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)

Overall Survival (OS): Overall Survival (OS) 
The time from date of randomisation to the date of progression or death due to any cause, whichever occurs earlier, up to approximately 42 months  
 
Secondary Outcome  
Outcome  TimePoints 
Investigator assessment of PFS2: PFS2 - time from randomisation to second progression or death due to any cause  Approximately up to 42 months 
Response Rate (ORR): percentage of patients with at least one investigator-assessed visit response of complete or partial response (as assessed by the investigator, using RECIST 1.1   Approximately up to 42 months 
Safety and tolerability of drugs by assessment of AEs/SAEs: Graded according to the National Cancer Institute (NCI CTCAE)   Approximately up to 42 months 
Minimum plasma concentration(Cmin), plasma concentration1-2 hours post-dose (C1-2h) and 4 hours post-dose (C4h) during months 1 and 2: Plasma PK parameters derived from a population model as data permits   During months 1 and 2 
EORTC QLQ BR23(European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module): The self-administered instrument includes 23-items and yields 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects).  Approximately up to 42 months  
The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items): 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), and global health status/QoL scale, along with 5 individual item symptom scores (appetite loss, dyspnoea, insomnia, constipation, and diarrhoea  Approximately up to 42 months 
Duration of Response (DoR): time from the date of first documented response until date of documented progression (as assessed by the investigator, using RECIST 1.1) or death in the absence of disease progression  Approximately up to 42 months  
Clinical Benefit Rate (CBR): number of patients with complete or partial response or with stable disease maintained ≥24 weeks (as assessed by the investigator, using RECIST 1.1) divided by the number of patients in the analysis  Approximately up to 42 months 
 
Target Sample Size
Modification(s)  
Total Sample Size="800"
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)   30/08/2019 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  25/06/2019 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="4"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
Brief Summary
Modification(s)  
This is a Phase III, double-blind, randomised study assessing the efficacy of capivasertib + paclitaxel vs placebo + paclitaxel as first-line treatment in patients with histologically confirmed, locally advanced (not amenable to resection with curative intent) or metastatic TNBC in the overall population and in the PIK3CA/AKT1/PTEN-altered sub-population (altered subgroup).  ‘PIK3CA/AKT1/PTEN-altered’ refers to a prespecified subgroup of patients whose tumours harbour qualifying activating mutation in PIK3CA or AKT1 and/or qualifying inactivating alteration in PTEN

Initially, enrolment will be open to all eligible patients irrespective of the PIK3CA/AKT1/PTEN status of their tumour(s); however, the prevalence of the subgroup of patients qualifying for the altered subgroup will be monitored post-randomisation via central testing of formalin-fixed paraffin-embedded (FFPE) tumour samples collected before study entry.  Based on emerging information during the course of the study, enrolment may be restricted to patients who qualify for the altered sub-population.   

Approximately 800 patients will be randomised in a 1:1 ratio to treatment with either capivasertib + paclitaxel or placebo + paclitaxel.  Randomisation will occur as soon as possible after commencement of screening and should be within 28 days of screening. 

The randomisation scheme will be stratified on the following factors:

1         Visceral vs non-visceral disease

2          (Neo)adjuvant chemotherapy: yes vs no

3          Geographic region: China, Asia-Pacific (excluding China), United States, Rest of the World

( Visceral disease is defined as lung, liver (including biliary tract), brain, pleural and/or peritoneal involvement.)

Paclitaxel will be administered as a weekly single intravenous (IV) infusion. Patients will receive 3 consecutive weekly paclitaxel infusions followed by 1 week off-treatment within each 28-day treatment cycle. 

Capivasertib/placebo will be continued until disease progression unless there is evidence of unacceptable toxicity, or if the patient requests to stop the study treatment.  Paclitaxel treatment will be continued for at least 6 cycles unless the patient experiences unacceptable toxicity that is attributed directly to treatment with paclitaxel.  If capivasertib/placebo is discontinued for reasons other than disease progression, the patient may continue on paclitaxel alone at the investigator’s discretion.  Likewise, if paclitaxel is discontinued for reasons other than disease progression, the patient may continue on capivasertib/placebo alone at the investigator’s discretion. 

RECIST tumour assessments will be performed using CT or MRI scans of the chest, abdomen and pelvis (with additional anatomy as clinically indicated by extent of disease) at baseline (no more than 28 days before the date of randomisation, as close as possible to the start of study treatment) and will be repeated every 8 weeks (±7 days) for the first 2 years and every 12 weeks (±7 days) thereafter, after start of treatment (Cycle 1, Week 1, Day 1) until objective radiological disease progression as defined by RECIST 1.1 (regardless of reason for treatment discontinuation).  Patients who discontinue treatment prior to progression should continue to be scanned until progression. 

An Independent Data Monitoring Committee (IDMC) will be established in order to assess the progress of the clinical study at regular intervals.  This will include reviewing unblinded safety and tolerability data and the data from the interim futility analysis in the non-altered subgroup in order to recommend to AstraZeneca whether or not to limit recruitment to the altered subgroup only. 

 
Close