Clinical Trials /

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

NCT03997123

Description:

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)

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC
  • Official Title: 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.

Clinical Trial IDs

  • ORG STUDY ID: D3614C00001
  • NCT ID: NCT03997123

Conditions

  • Triple Negative Breast Neoplasms

Interventions

DrugSynonymsArms
CapivasertibAZ5363Capivasertib + Paclitaxel
PaclitaxelCapivasertib + Paclitaxel
PlaceboPlacebo tablets to match capivasertibPlacebo + Paclitaxel

Purpose

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)
    

Trial Arms

NameTypeDescriptionInterventions
Capivasertib + PaclitaxelExperimentalPaclitaxel: 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.
  • Capivasertib
  • Paclitaxel
Placebo + PaclitaxelPlacebo ComparatorPaclitaxel: 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.
  • Paclitaxel
  • Placebo

Eligibility Criteria

        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
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)

Secondary Outcome Measures

Measure:Investigator assessment of PFS2
Time Frame:Time from randomization to second progression or death due to any cause up to approximately 42 months
Safety Issue:
Description:PFS2 - time from randomisation to second progression or death
Measure:Response Rate (ORR)
Time Frame:Up to approximately 42 months
Safety Issue:
Description: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)
Measure:Safety and tolerability of drugs by assessment of AEs/SAEs
Time Frame:Up to approximately 42 months
Safety Issue:
Description:Graded according to the National Cancer Institute (NCI CTCAE)
Measure: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
Safety Issue:
Description:Plasma PK parameters derived from a population model as data permits
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Duration of Response (DoR)
Time Frame:Up to approximately 42 months
Safety Issue:
Description: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.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to approximately 42 months
Safety Issue:
Description: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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Breast Cancer;
  • Triple-negative Breast Cancer

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