Informations générales (source: ClinicalTrials.gov)
A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib + Docetaxel Versus Placebo + Docetaxel as Treatment for Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
Interventional
Phase 3
AstraZeneca (Voir sur ClinicalTrials)
mars 2022
mars 2026
10 septembre 2025
This study will assess the efficacy and safety of capivasertib plus docetaxel versus
placebo plus docetaxel in participants with metastatic castration resistant prostate
cancer (mCRPC), all participants will receive the docetaxel with steroid therapy and
receive androgen deprivation therapy. The intention of the study is to demonstrate that
the combination of capivasertib plus docetaxel is superior to placebo plus docetaxel with
respect to the overall survival and/or the radiographic progression free survival of
study participants.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Anna PATRIKIDOU | 28/05/2024 10:27:07 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| HIA BEGIN | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Research Site - 29609 - Brest - France | Contact (sur clinicalTrials) | ||||
| Research Site - 33076 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| Research Site - 34298 - Montpellier - France | Contact (sur clinicalTrials) | ||||
| Research Site - 44805 - Saint Herblain Cedex - France | Contact (sur clinicalTrials) | ||||
| Research Site - 54000 - Vandoeuvre Les Nancy - France | Contact (sur clinicalTrials) | ||||
| Research Site - 63011 - Clermont-Ferrand CEDEX 01 - France | Contact (sur clinicalTrials) | ||||
| Research Site - 67000 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Research Site - 67033 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Research Site - 75014 - Paris - France | Contact (sur clinicalTrials) | ||||
| Research Site - 75020 - Paris - France | Contact (sur clinicalTrials) | ||||
| Research Site - 76031 - Rouen - France | Contact (sur clinicalTrials) | ||||
| Research Site - 94010 - Creteil - France | Contact (sur clinicalTrials) | ||||
| Research Site - 94805 - Villejuif Cedex - France | Contact (sur clinicalTrials) | ||||
Critères
Homme
Inclusion Criteria:
- Histologically-confirmed prostate adenocarcinoma without predominant neuroendocrine
or small cell cancers
- Metastatic disease documented prior to randomisation by clear evidence of ≥ 1 bone
lesion (defined as 1 lesion with positive uptake on bone scan) and/or ≥ 1 soft
tissue lesion (measurable or non-measurable)
- Patient must have been previously treated with a next generation hormonal agent
(NHA), ie, abiraterone, enzalutamide, apalutamide or darolutamide, for prostate
cancer for at least 3 months and shown evidence of disease progression (radiological
or via PSA assessment) while receiving the NHA
- Evidence of mCRPC with progression of disease despite androgen deprivation therapy
(ADT)
- Serum testosterone level ≤ 50 ng/dL
- Candidate for docetaxel and steroid therapy
- Ongoing ADT with LHRH agonist, LHRH antagonist, or bilateral orchiectomy
- Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO)
performance status 0 to 1 and anticipated minimum life expectancy of 12 weeks
- Confirmation that archival formalin-fixed paraffin-embedded (FFPE) tumour tissue
sample which meets the minimum pathology and sample requirements is available to
send to the central laboratory
- Able and willing to swallow and retain oral medication
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agreement to refrain from donating sperm
- Histologically-confirmed prostate adenocarcinoma without predominant neuroendocrine
or small cell cancers
- Metastatic disease documented prior to randomisation by clear evidence of ≥ 1 bone
lesion (defined as 1 lesion with positive uptake on bone scan) and/or ≥ 1 soft
tissue lesion (measurable or non-measurable)
- Patient must have been previously treated with a next generation hormonal agent
(NHA), ie, abiraterone, enzalutamide, apalutamide or darolutamide, for prostate
cancer for at least 3 months and shown evidence of disease progression (radiological
or via PSA assessment) while receiving the NHA
- Evidence of mCRPC with progression of disease despite androgen deprivation therapy
(ADT)
- Serum testosterone level ≤ 50 ng/dL
- Candidate for docetaxel and steroid therapy
- Ongoing ADT with LHRH agonist, LHRH antagonist, or bilateral orchiectomy
- Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO)
performance status 0 to 1 and anticipated minimum life expectancy of 12 weeks
- Confirmation that archival formalin-fixed paraffin-embedded (FFPE) tumour tissue
sample which meets the minimum pathology and sample requirements is available to
send to the central laboratory
- Able and willing to swallow and retain oral medication
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agreement to refrain from donating sperm
- Radiotherapy with a wide field of radiation within 4 weeks before start of study
treatment
- Major surgery (excl. placement of vascular access, transurethral resection of
prostate, bilateral orchiectomy, internal stents) within 4 weeks of start of study
treatment
- Brain metastases,or spinal cord compression (unless spinal cord compression is
asymptomatic and stable and not requiring steroids for at least 4 weeks prior to
start of study treatment)
- Any of the following cardiac criteria:
i. Mean resting corrected QT interval (QTc) >470 msec from 3 consecutive ECGs ii.
Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG 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 3 months: coronary artery bypass graft, vascular stent,
myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade
≥2 v. Symptomatic hypotension - systolic blood pressure <90 mmHg and/or diastolic
blood pressure <50 mmHg vi. haemodinamic instability
- Clinically significant abnormalities of glucose metabolism as defined by any of the
following:
i. Patients with diabetes mellitus (DM) type 1 or DM 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 10^9/L ii. Platelet count < 100x 10^9/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
clearance < 50 mL/min per the Cockcroft and Gault formula without the need for
chronic dialysis;
- As judged by the investigator, any evidence of diseases (including severe or
uncontrolled systemic diseases, uncontrolled hypertension, history of interstitial
pneumonia / pneumonitis or interstitial lung disease, renal transplant and active
bleeding diseases), which, in the investigator's opinion, makes it undesirable for
the patient to participate in the study or that would jeopardise compliance with the
protocol.
- 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, 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
- History of another primary malignancy except for malignancy treated with curative
intent with no known active disease ≥2 years before the first dose of study
intervention and of low potential risk for recurrence. Exceptions include adequately
resected non-melanoma skin cancer and curatively treated in situ disease.
- Persistent toxicities (CTCAE Grade ≥2) caused by previous anticancer therapy,
excluding alopecia. Patients with irreversible toxicity that is not reasonably
expected to be exacerbated by study intervention in the opinion of the investigator
may be included (eg, hearing loss)
- Known to have active hepatitis infection.
- Known to have human immunodeficiency virus (HIV) with a detectable viral RNA load or
a CD4+ T-cell count < 350 cells/uL or a history of an acquired immunodeficiency
syndrome (AIDS)-defining opportunistic infection within the past 12 months, or
receiving anti-HIV medications for less than 4 weeks.
- Known to have active tuberculosis infection (clinical evaluation that may include
clinical history, physical examination and radiographic findings, or tuberculosis
testing in line with local practice).
- Treatment with any of the following:
i. Prior chemotherapy for CRPC. Chemotherapy for metastatic or localized HSPC
(including docetaxel) is allowed provided that chemotherapy was completed ≥ 6months
before randomisation and progression of the prostate cancer occurred ≥ 6months after
the completion of therapy.
ii. Prior exposure to AKT inhibitors or PI3K inhibitors iii. 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 iv. Any other immunotherapy,
immunosuppressant medication (other than corticosteroids) or anticancer agents (except
ADT) within 3 weeks of the first dose of study treatment v. Strong inhibitors or strong
inducers of cytochrome P450 (CYP)3A4 within 2 weeks prior to the first dose of study
treatment (3 weeks for St John's wort), vi.Use of any live vaccine administration 30 days
prior to the initiation of study treatment, during, and for at least 90 days after the
last dose of the study treatment
- Drugs known to significantly prolong the QT interval and associated with Torsade de
Pointes within 5 half-lives of the first dose of study treatment
- History of hypersensitivity to active or inactive excipients of capivasertib,
docetaxel, 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 docetaxel