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Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC (CapItello290)

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: NCT03997123
Recruitment Status : Recruiting
First Posted : June 25, 2019
Last Update Posted : July 16, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE May 20, 2019
First Posted Date  ICMJE June 25, 2019
Last Update Posted Date July 16, 2020
Actual Study Start Date  ICMJE June 25, 2019
Estimated Primary Completion Date June 10, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • Progression-Free Survival (PFS) [ Time Frame: 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 ]
    Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)
  • Overall Survival (OS) [ Time Frame: The time from date of randomisation to the date of death due to any cause up to approximately 42 months ]
    Overall Survival (OS)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • Investigator assessment of PFS2 [ Time Frame: Time from randomization to second progression or death due to any cause up to approximately 42 months ]
    PFS2 - time from randomisation to second progression or death
  • Response Rate (ORR) [ Time Frame: Up to approximately 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)
  • Safety and tolerability of drugs by assessment of AEs/SAEs [ Time Frame: Up to approximately 42 months ]
    Graded according to the National Cancer Institute (NCI CTCAE)
  • Minimum plasma concentration(Cmin), plasma concentration1-2 hours post-dose (C1-2h) and 4 hours post-dose (C4h) during months 1 and 2 [ Time Frame: During months 1 and 2 ]
    Plasma PK parameters derived from a population model as data permits
  • EORTC QLQ BR23(European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module) [ Time Frame: approximately up to 42 months ]
    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). Items are scored on a 4-point verbal rating scale: "Not at All," "A Little," "Quite a Bit," and "Very Much". Scores are transformed to a 0 to 100 scale, where higher scores indicate better unctioning, better HRQoL, or greater level of symptom.
  • The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items) [ Time Frame: approximately up to 42 months ]
    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. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales/scores represent greater symptom severity.
  • Duration of Response (DoR) [ Time Frame: Up to approximately 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.
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC
Official Title  ICMJE A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib/+Paclitaxel vs Placebo+Paclitaxel as First-line Treatment for Patients With Locally Advanced (Inoperable) or Metastatic TNBC.
Brief Summary Phase III Study of Capivasertib + Paclitaxel versus Placebo + Paclitaxel as First line Treatment for Patients with Locally Advanced or Metastatic Triple-negative Breast Cancer (TNBC)
Detailed Description A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Paclitaxel Versus Placebo + Paclitaxel as First-line Treatment for Patients with Histologically Confirmed, Locally Advanced (Inoperable) or Metastatic Triple negative Breast Cancer (TNBC)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Double-blind Randomised Study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Neoplasms
Intervention  ICMJE
  • Drug: Capivasertib
    400 mg (2 oral tablets) given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle. 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.
    Other Name: AZ5363
  • Drug: Paclitaxel
    80 mg/m2 concentrate for solution for infusion, 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle. Paclitaxel treatment will be continued for at least 6 cycles unless the patient experiences unacceptable toxicity that is attributed directly to treatment with paclitaxel.
  • Drug: Placebo
    Placebo: Oral tablets. 400 mg of Placebo (2 tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week offtreatment within each 28-day treatment cycle
    Other Name: Placebo tablets to match capivasertib
Study Arms  ICMJE
  • Experimental: Capivasertib + Paclitaxel

    Paclitaxel: Intravenous infusion. 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle.

    Capivasertib: Oral tablets. 400 mg of Capivasertib (2 tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle.

    Interventions:
    • Drug: Capivasertib
    • Drug: Paclitaxel
  • Placebo Comparator: Placebo + Paclitaxel

    Paclitaxel: Intravenous infusion. 3 consecutive weekly infusions of 80 mg/m2 (given on Day 1 of Weeks 1, 2, and 3), followed by 1 week off-treatment within each 28-day treatment cycle.

    Placebo: Oral tablets. 400 mg of Placebo (2 tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 2 to 5 of Weeks 1, 2, and 3 followed by 1 week off-treatment within each 28-day treatment cycle.

    Interventions:
    • Drug: Paclitaxel
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 24, 2019)
800
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2023
Estimated Primary Completion Date June 10, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed TNBC from most recently collected tumour tissue sample
  2. Metastatic or locally recurrent disease; locally recurrent disease most not be amenable to resection with curative intent (patient who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible)
  3. ECOG/WHO PS: 0-1
  4. Measurable disease according to RECIST 1.1 and/or lytics or mixedbone lesions that can be assessed by CT or MRI in the absence of measurable disease
  5. FFPE tumour sample from primary/recurrent cancer

Exclusion Criteria:

  1. Prior chemotherapy in the (neo)adjuvant setting within 12 months from the end of chemotherapy to inclusion into this study
  2. Prior systematic therapy for inoperable locally advanced or metastatic disease
  3. Prior treatment with any of the following:

    • AKT, PI3K, and/or mTOR inhibitors
    • Capivasertib in the present study (ie, any dosing with capivasertib due to previous participation in this study)
    • 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 halflife (eg, biologics) as agreed by the sponsor
    • 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.
  4. Radiotherapy with a wide field of radiation within 4 weeks before the first dose of study treatment (capivasertib/placebo)
  5. Pre-existing sensory or motor polyneuropathy ≥grade 2 according to NCI CTCAE v5
  6. With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment
  7. Any of the following cardiac criteria at screening:

    • Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive ECGs
    • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block)
    • 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
    • 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
    • Uncontrolled hypotension - SBP <90 mmHg and/or DBP <50 mmHg
    • Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiplegated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive).
  8. Clinically significant abnormalities of glucose metabolism as defined by any of the following at screening:

    • Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment
    • HbA1c ≥8.0% (63.9 mmol/mol)
  9. Inadequate bone marrow reserve or organ function at screening
  10. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Argentina,   Brazil,   Canada,   China,   Czechia,   France,   India,   Japan,   Korea, Republic of,   Mexico,   Peru,   Philippines,   Poland,   Portugal,   Russian Federation,   Saudi Arabia,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03997123
Other Study ID Numbers  ICMJE D3614C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.
Supporting Materials: Study Protocol
Supporting Materials: 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 de-identified 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
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter Schmid, MD,PhD,FRCP Centre for Experimental Cancer Medicine (CECM), Barts Cancer Institute
PRS Account AstraZeneca
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP