Montag, 14. Juni 2021
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JOURNAL ONKOLOGIE – STUDIE
CAPItello-281

Capivasertib+Abiraterone as Treatment for Patients With Metastatic Hormone-sensitive Prostate Cancer and PTEN Deficiency

Rekrutierend

NCT-Nummer:
NCT04493853

Studienbeginn:
Juli 2020

Letztes Update:
03.06.2021

Wirkstoff:
Capivasertib, abiraterone acetate

Indikation (Clinical Trials):
Prostatic Neoplasms, Hypersensitivity

Geschlecht:
Männer

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 309)

Research Site
10117 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
47179 Duisburg
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
79312 Emmendingen
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
44625 Herne
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
40822 Mettmann
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
48149 Münster
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
90419 Nürnberg
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
72622 Nürtingen
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Research Site
46483 Wesel
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
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92037 La Jolla
United StatesNoch nicht rekrutierend» Google-Maps
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92868 Orange
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80211 Denver
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80401 Golden
United StatesNoch nicht rekrutierend» Google-Maps
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33901-8101 Fort Myers
United StatesNoch nicht rekrutierend» Google-Maps
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33401 West Palm Beach
United StatesNoch nicht rekrutierend» Google-Maps
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60637 Chicago
United StatesNoch nicht rekrutierend» Google-Maps
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60134 Geneva
United StatesNoch nicht rekrutierend» Google-Maps
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52242 Iowa City
United StatesNoch nicht rekrutierend» Google-Maps
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66205 Fairway
United StatesNoch nicht rekrutierend» Google-Maps
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59715 Bozeman
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03756 Lebanon
United StatesNoch nicht rekrutierend» Google-Maps
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07631 Englewood
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10461 Bronx
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14642 Rochester
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27710 Durham
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45219 Cincinnati
United StatesNoch nicht rekrutierend» Google-Maps
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43210 Columbus
United StatesNoch nicht rekrutierend» Google-Maps
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17604 Lancaster
United StatesNoch nicht rekrutierend» Google-Maps
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75063 Irving
United StatesNoch nicht rekrutierend» Google-Maps
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84112 Salt Lake City
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98104 Seattle
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Research Site
B1884BBF Berazategui
ArgentinaNoch nicht rekrutierend» Google-Maps
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1426 Buenos Aires
ArgentinaNoch nicht rekrutierend» Google-Maps
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S2000DEJ Rosario
ArgentinaNoch nicht rekrutierend» Google-Maps
Research Site
4600 San Salvador de Jujuy
ArgentinaRekrutierend» Google-Maps
Research Site
14784-400 Barretos
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
90050-170 Porto Alegre
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
90160-093 Porto Alegre
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
20230-130 Rio de Janeiro
BrazilNoch nicht rekrutierend» Google-Maps
Research Site
15090-000 São José do Rio Preto
BrazilRekrutierend» Google-Maps
Research Site
25030 Besançon Cedex
FranceNoch nicht rekrutierend» Google-Maps
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69495 Pierre Benite
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29107 Quimper Cedex
FranceNoch nicht rekrutierend» Google-Maps
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35033 Rennes Cedex 9
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4400 Nyíregyháza
HungaryNoch nicht rekrutierend» Google-Maps
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13620 Seongnam-si
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06591 Seoul
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0 3100 Mexico City
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2545 CH Den Haag
NetherlandsNoch nicht rekrutierend» Google-Maps
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6162 BG Sittard-Geleen
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5042AD Tilburg
NetherlandsNoch nicht rekrutierend» Google-Maps
Research Site
2600 Baguio City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
6000 Cebu City
PhilippinesNoch nicht rekrutierend» Google-Maps
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8000 Davao City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
1101 Quezon City
PhilippinesNoch nicht rekrutierend» Google-Maps
Research Site
117997 Moscow
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
151059 Moscow
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
630082 Novisibirsk
Russian FederationRekrutierend» Google-Maps
Research Site
630007 Novosibirsk
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
190103 Saint-Petersburg
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Research Site
197758 St. Petersburg
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
191014 St.Petersburg
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Research Site
634028 Tomsk
Russian FederationNoch nicht rekrutierend» Google-Maps
Research Site
7505 Western Cape
South AfricaNoch nicht rekrutierend» Google-Maps
Research Site
GU2 7XX Guildford
United KingdomNoch nicht rekrutierend» Google-Maps
Research Site
PL6 8DH Plymouth
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Research Site
123 Ho Chi Minh City
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Alle anzeigen

Studien-Informationen

Brief Summary:

This study will assess the efficacy and safety of capivasertib plus abiraterone

(+prednisone/prednisolone) plus androgen deprivation therapy (ADT) versus placebo plus

abiraterone (+prednisone/prednisolone) plus ADT in participants with mHSPC whose tumours are

characterised by PTEN deficiency. The intention of the study is to demonstrate that in

participants with mHSPC, the combination of capivasertib plus abiraterone

(+prednisone/prednisolone) plus ADT is superior to placebo plus abiraterone

(+prednisone/prednisolone) plus ADT in participants with mHSPC characterised by PTEN

deficiency with respect to radiographic progression-free survival (rPFS) per 1) Response

Evaluation Criteria in Solid Tumors (RECIST) 1.1 for soft tissue and/or Prostate Cancer

Working Group (PCWG3) for bone as assessed by the investigator 2) death due to any cause.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Asymptomatic or mildly symptomatic, histologically-confirmed de novo metastatic

hormone-sensitive prostate adenocarcinoma without small-cell tumours

- Provide a FFPE tissue block (preferred) or slides. Tissue from bone metastases is not

acceptable

- A valid PTEN IHC result indicating PTEN deficiency (centralized testing)

- Metastatic disease documented prior to randomisation by clear evidence of ≥ 1 bone

lesion and/or ≥ 1 soft tissue lesion accurately assessed at baseline and suitable for

repeated assessment with CT and/or MRI. PSMA PET identification only will not be

eligible

- Candidate for abiraterone and steroid therapy

- Ongoing ADT with GnRH analogue, or LHRH agonists or antagonist, or bilateral

orchiectomy (regardless of method) is from 0 days to a max. of 3 months prior to

randomisation

- Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0 to 1 with no

deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks

- Able and willing to swallow and retain oral medication

- 7-day Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory(BFI)

questionnaires and the analgesic diary during screening completed

- Agreement to remain abstinent (refrain from heterosexual intercourse) or use

contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

- Radiotherapy with a wide field of radiation within 4 weeks before the start of study

treatment (capivasertib/placebo)

- Major surgery (excluding placement of vascular access, transurethral resection of

prostate, bilateral orchiectomy, or internal stents) within 4 weeks of the start of

study treatment

- Brain metastases, or spinal cord compression (unless spinal cord compression is

asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior

to start of study treatment)

- 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

- Any of the following cardiac criteria:

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.

Clinically significant heart disease as evidenced by myocardial infarction, or

arterial thrombotic events in the past 6 months, severe or unstable angina, or NYHA or

Class II to IV heart failure or cardiac ejection fraction measurement of < 50% v.

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 NYHA Grade ≥ 2 vi. Uncontrolled hypotension

- systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <50

mmHg vii. 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) viii.

Uncontrolled hypertension (SBP ≥ 160 mmHg or DBP ≥ 95 mmHg).

- Clinically significant abnormalities of glucose metabolism as defined by any of the

following:

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

insulin treatment ii. HbA1c ≥8.0% (63.9 mmol/mol)

- Inadequate bone marrow reserve or organ function as demonstrated by any of the

following laboratory values:

i. Absolute neutrophil count < 1.5x 109/L ii. Platelet count < 100x 109/L iii.

Haemoglobin < 9 g/dL (< 5.59 mmol/L) iv. Alanine aminotransferase (ALT) and aspartate

aminotransferase (AST) > 2.5x upper limit of normal (ULN) if no demonstrable liver

metastases or > 5x ULN in the presence of liver metastases. Elevated alkaline

phosphatase (ALP) is not exclusionary if due to the presence of bone metastases and

liver function is otherwise considered adequate in the investigator's judgement v.

Total bilirubin > 1.5x ULN (participants with confirmed Gilbert's syndrome may be

included in the study with a higher value) vi. Creatinine > 1.5x 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 >

1.5x ULN

- As judged by the investigator, any evidence of severe or uncontrolled systemic

diseases, including active bleeding diatheses, or known active infection including

hepatitis B, hepatitis C, and HIV

- unevaluable for both bone and soft tissue progression as defined by meeting both of

the following criteria: i. a "superscan" of bone scan, and ii. no soft tissue lesion

that can be assessed by RECIST criteria

- 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

- 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 contra-indicates 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

- Evidence of dementia, altered mental status, or any psychiatric condition that would

prohibit understanding or rendering of informed consent

- Previous allogeneic bone marrow transplant or solid organ transplant

- Known additional malignancy that has had progression or has required active treatment

in the last 3 years. Exceptions include basal cell carcinoma of the skin, and squamous

cell carcinoma of the skin that has undergone potentially curative therapy

- Treatment with any of the following:

i. Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment ii.

Any investigational agents or study drugs from a previous clinical study within 30

days or 5 half-lives (whichever is longer) of the first dose of study treatment iii.

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) iv. Potent inhibitors or inducers of CYP3A4 within 2 weeks before the start

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 before the start

of study treatment

- Drugs known to prolong the QT interval within 5 half-lives of the first dose of study

treatment

- History of hypersensitivity to active or inactive excipients of capivasertib,

abiraterone, or drugs with a similar chemical structure or class

- Any restriction or contraindication based on the local prescribing information that

would prohibit the use of abiraterone

Studien-Rationale

Primary outcome:

1. Radiographic Progression-free Survival (rPFS) (Time Frame - Up to approximately 52 months):
rPFS is defined as the time from randomisation to radiographic progression, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) for soft tissue and/or Prostate Cancer Working Group 3 (PCWG3) for bone, or death due to any cause for each study arm.



Secondary outcome:

1. Overall survival (OS) (Time Frame - Up to approximately 64 months):
Overall survival is the length of time from randomisation until the date of death due to any cause.

2. Time to Start of First Subsequent Therapy or Death (TFST) (Time Frame - Up to approximately 52 months):
TFST is defined as time from randomisation to the earlier of: the start date of the first subsequent anticancer therapy after discontinuation of randomised treatment (capivasertib/placebo), or death due to any cause.

3. Symptomatic Skeletal Event-Free Survival (SSE-FS) (Time Frame - Up to approximately 64 months):
SSE-FS is defined as time from randomisation until any of the following: use of radiation therapy to prevent or relieve skeletal symptoms; Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral); Occurrence of spinal cord compression; Orthopaedic surgical intervention for bone metastasis; Death due to any cause.

4. Time to Pain Progression (TTPP) (Time Frame - Up to approximately 64 months):
TTPP is defined as the time from randomisation to clinically meaningful pain progression base on a 2-point increase from baseline in the Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("worst pain in 24 hours") score and/or initiation of/increase in opiate analgesic use.

5. Time to PSA progression (Time Frame - Up to approximately 52 months):
The time from randomisation to PSA progression, as determined by PCWG3 criteria.

6. Time To Castration Resistance (TTCR) (Time Frame - Up to approximately 64 months):
TTCR is defined as the time from randomisation to the first castration-resistant event (radiographic disease progression, PSA progression, or SSE), whichever occurs first, with castrate levels of testosterone (below 50 ng/dL).

7. Fatigue intensity, severity and interference domains assessed by the Brief Fatigue Inventory (BFI) (Time Frame - Up to approximately 64 months):
BFI endpoints may include: Time to deterioration in fatigue intensity; Time to deterioration in fatigue interference; Change from baseline in fatigue severity and fatigue interference domain scores.

8. Overall Pain Severity and Pain Interference as assessed by BPI-SF questionnaire (Time Frame - Up to approximately 64 months):
BPI-SF: Change from baseline in pain severity and pain interference domain scores.

9. Disease-Related Symptoms and HRQoL using the Functional Assessment of Cancer Therapy - Prostate Cancer (FACT-P) questionnaire (Time Frame - Up to approximately 64 months):
FACT-P endpoints may include: Time to deterioration in FACT-P scores; Change from baseline in FACT-P scores.

10. Progression-Free Survival after next-line treatment (PFS2) (Time Frame - Up to approximately 64 months):
PFS2 is defined as time from randomisation until progression on next-line treatment, as clinical progression, PSA progression, or radiographic progression determined by RECIST version 1.1 (soft tissue) and/or PCWG3 criteria (bone), as assessed by the investigator, or death due to any cause.

11. Plasma concentration of capivasertib pre-dose (Time Frame - Cycle 1 Day 15, Cycle 2 Day 1, Cycle Day 15)

12. Plasma concentration of capivasertib 1h post-dose (Time Frame - Cycle 1 Day 1)

13. Plasma concentration of capivasertib 4h post-dose (Time Frame - Cycle 1 Day 1)

Studien-Arme

  • Experimental: Capivasertib + Abiraterone
    Participants receive capivasertib in combination with abiraterone (prednisone/prednisolone) on a background of ADT.
  • Placebo Comparator: Placebo + Abiraterone
    Participants receive placebo in combination with abiraterone (prednisone/prednisolone) on a background of ADT.

Geprüfte Regime

  • 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. Number of Cycles: until disease progression or unacceptable toxicity develops.
  • Placebo:
    matched to capivasertib appearance (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. Number of Cycles: until disease progression or unacceptable toxicity develops.
  • Abiraterone Acetate (ZYTIGA):
    Administered orally as tablets at a dosage of 1000 mg daily. Administered continuously until criteria for discontinuation are met.

Quelle: ClinicalTrials.gov


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