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Imfinzi NSCLC
Imfinzi NSCLC
JOURNAL ONKOLOGIE – STUDIE
CAPItello-291

Capivasertib+Fulvestrant vs Placebo+Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic HR+/HER2- Breast Cancer

Rekrutierend

NCT-Nummer:
NCT04305496

Studienbeginn:
April 2020

Letztes Update:
23.03.2021

Wirkstoff:
Fulvestrant, Capivasertib, Placebo

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
AstraZeneca

Collaborator:
-

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 241)

Research Site
45130 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
60431 Frankfurt am Main
(Hessen)
GermanyRekrutierend» Google-Maps
Research Site
45879 Gelsenkirchen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
30625 Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Research Site
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
24105 Kiel
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Research Site
68167 Mannheim
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
32429 Minden
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
81675 München
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
48149 Münster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
33161 Paderborn
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Research Site
14467 Potsdam
(Brandenburg)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
91361-5231 Thousand Oaks
United StatesRekrutierend» Google-Maps
Research Site
64132-1136 Kansas City
United StatesRekrutierend» Google-Maps
Research Site
10065 New York
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
C1125ABD Ciudad Autonoma De Buenos Aire
ArgentinaRekrutierend» Google-Maps
Research Site
L5M 2N1 Mississauga
CanadaNoch nicht rekrutierend» Google-Maps
Research Site
310022 Gongshu District
ChinaNoch nicht rekrutierend» Google-Maps
Research Site
450008 Zhengzhou City
ChinaNoch nicht rekrutierend» Google-Maps
Research Site
13620 Seongnam-si
Korea, Republic ofRekrutierend» Google-Maps
Research Site
111123 Moscow
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
115478 Moscow
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Research Site
198255 Saint-Petersburg
Russian FederationRekrutierend» Google-Maps
Research Site
354000 Sochi
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
08907 Hosp de Llobregat(Barcelona)
SpainRekrutierend» Google-Maps
Research Site
FY3 8NR Blackpool
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
BS2 8ED Bristol
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
DE22 3NE Derby
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
HD3 3EA Huddersfield
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
LA1 4RP Lancaster
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
BD7 1DP Leeds
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
N18 1QX London
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
NW3 2QG London
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
SE18 4QH London
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
YO31 8HE York
United KingdomNoch nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

Phase III, double-blind, randomised study assessing the efficacy of capivasertib +

fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced

(inoperable) or metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor

2 Negative (HR+/HER2-) breast cancer following recurrence or progression on or after

aromatase inhibitor (AI) therapy.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Adult females, pre- and/or post-menopausal, and adult males. Pre-menopausal (and

peri-menopausal) women can be enrolled if amenable to treatment with an LHRH agonist.

Patients are to have commenced concomitant treatment with LHRH agonist at least 4

weeks prior to Cycle 1, Day 1 and must be willing to continue on it for the duration

of the study

2. Histologically confirmed HR+/HER2- breast cancer determined from the most recent

tumour sample (primary or metastatic), as per the American Society of Clinical

Oncology and College of American Pathologists guideline recommendations. To fulfil the

requirement of HR+ disease, a breast cancer must express ER with or without

co-expression of progesterone receptor.

3. Metastatic or locally advanced disease with radiological or objective evidence of

recurrence or progression; 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)

4. ECOG/WHO PS: 0-1

5. Patients are to have received treatment with an AI containing regimen (single agent or

in combination) and have:

1. Radiological evidence of breast cancer recurrence or progression while on, or

within 12 months of the end of (neo)adjuvant treatment with an AI, OR

2. Radiological evidence of progression while on prior AI administered as a

treatment line for locally advanced or metastatic breast cancer (this does not

need to be the most recent therapy)

6. Patients must have measurable disease according to RECIST 1.1 and/or at least 1 lytic

or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients

with sclerotic/osteoblastic bone lesions only in the absence of measurable disease are

not eligible

7. FFPE tumour sample from primary/recurrent cancer for central testing

Exclusion Criteria:

1. Symptomatic visceral disease or any disease burden that makes the patient ineligible

for endocrine therapy per the investigator's best judgement

2. More than 2 lines of endocrine therapy for inoperable locally advanced or metastatic

disease

3. More than 1 line of chemotherapy for inoperable locally advanced or metastatic

disease. Adjuvant and neoadjuvant chemotherapy are not classed as lines of

chemotherapy for advanced breast cancer

4. Prior treatment with any of the following:

1. AKT, PI3K and mTOR inhibitors

2. Fulvestrant, and other SERDs

3. Any other chemotherapy, immunotherapy, immunosuppressant medication (other than

corticosteroids) or anticancer agents within 3 weeks prior to study treatment

initiation.

4. 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

study treatment initiation.

5. Radiotherapy with a wide field of radiation up to 4 weeks before study treatment

initiation (capivasertib/placebo) and/or radiotherapy with a limited field of

radiation for palliation up to 2 weeks before study treatment initiation

(capivasertib/placebo)

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. Spinal cord compression or brain metastases unless asymptomatic, treated and stable

and not requiring steroids up to 4 weeks before study treatment initiation

8. Any of the following cardiac criteria:

1. Mean resting corrected QT interval (QTc) >470 msec obtained from 3 consecutive

ECGs

2. Any clinically important abnormalities in rhythm, conduction or morphology of

resting ECG (eg, complete left bundle branch block, third degree heart block)

3. 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

4. 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

5. Uncontrolled hypotension - systolic blood pressure <90 mmHg and/or diastolic

blood pressure <50 mmHg

6. 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:

1. Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring

insulin treatment

2. HbA1c ≥8.0% (63.9 mmol/mol)

10. Known abnormalities in coagulation such as bleeding diathesis, or treatment with

anticoagulants precluding intramuscular injections of fulvestrant or LHRH (if

applicable)

11. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding

Studien-Rationale

Primary outcome:

1. Progression-Free Survival (PFS) in the overall population (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 51 months):
Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)



Secondary outcome:

1. PFS in PIK3CA/AKT1/PTEN-altered subgroup (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 51 months):
Progression-Free Survival by investigator assessment (in accordance with RECIST 1.1)

2. Overall Survival (OS) (Time Frame - The time from date of randomisation to the date of death due to any cause up to 51 months):
Overall Survival (OS)

3. Investigator assessment of PFS2 (Time Frame - The time from the date of randomisation to the date of progression subsequent to the first subsequent therapy, or death due to any cause, whichever occurs earlier, up to approximately 51 months):
PFS2 - time from randomisation to second progression by investigator assessment

4. Response Rate (ORR) (Time Frame - Up to Approximately 51 months):
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)

5. Duration of Response (DoR) (Time Frame - Up to Approximately 51 months):
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

6. Clinical Benefit Rate (CBR) (Time Frame - Up to Approximately 51 months):
number of patients with complete or partial response or with stable disease maintained ≥24 weeks after randomisation (as assessed by the investigator, using RECIST 1.1)

7. ocurrence/frequency of AEs and its relationship to study drugs (safety and tolerability) (Time Frame - Up to Approximately 51 months):
AEs graded according to the National Cancer Institute (NCI CTCAE)

8. plasma concentration of capivasertib (Time Frame - Minimum plasma concentration (Cmin), plasma concentration 1 hour post-dose (C1h) and 4 hours post-dose (C4h) during cycles 1 and 2 (each cycle is 28 days)):
plasma concentration of capivasertib pre-dose and post-dose (C1h and C4h) in the overall population

9. EORTC QLQ BR23(European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module) (Time Frame - Up to Approximately 51 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

10. The EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items) (Time Frame - Up to Approximately 51 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

11. Time to definitive deterioration of the ECOG (Eastern Cooperative Oncology Group) performance status (Time Frame - Up to approximately 51 months):
Time from randomisation to the earlier of the date of the first definitive deterioration or death due to any cause. Deterioration is defined as a 1-point decrease in ECOG score from baseline, and the deterioration is considered definitive if no improvements in the ECOG performance status are observed at a subsequent time of measurement during the treatment period, or at no further assessments following the time point where the deterioration is observed

Studien-Arme

  • Experimental: Capivasertib + fulvestrant
    Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Capivasertib: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle.
  • Placebo Comparator: Placebo + fulvestrant
    Fulvestrant: 2 intramuscular injections of 500 mg given on Day 1 of Weeks 1 and 3 of cycle 1, and then on Day 1, Week 1 of each cycle thereafter. Placebo: 400 mg (2 oral tablets) BD given on an intermittent weekly dosing schedule. Dosed on Days 1 to 4 in each week of a 28-day treatment cycle.

Geprüfte Regime

  • Fulvestrant:
    Patients will be administered 500 mg (2 injections) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter
  • Capivasertib:
    400 mg (2 tablets) BD given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle
  • Placebo:
    400 mg of placebo (2 tablets) BD given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week of a 28-day treatment cycle

Quelle: ClinicalTrials.gov


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