Study of Capivasertib + Docetaxel vs Placebo + Docetaxel as Treatment for Metastatic Castration Resistant Prostate Cancer (mCRPC)

Prostate Cancer Clinical Trial

— CAPItello280  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05348577
• Other study ID #: D361EC00001
• Secondary ID: 2023-504996-2620
• Status: Recruiting
• Phase: Phase 3
• Start date: March 25, 2022
• Est. completion date: December 21, 2026

Study information

• Verified date: March 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 of study participants, when overall survival is defined as the time from randomization until the date of death due to any cause.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 790
• Est. completion date: December 21, 2026
• Est. primary completion date: October 23, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 130 Years

Eligibility

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

Exclusion Criteria:

• 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 CD4+ T-cell count < 350 cells/uL or a history of an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months.
• 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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• capivasertib
320 mg (2 tablets) BD given on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5, 9 to 12, and 16 to 19 in each week of a 21-day treatment cycle. Number of Cycles: until disease progression or unacceptable toxicity develops, death, or if the patient requests to stop the study treatment.
• docetaxel
Patients will receive docetaxel in intravenous infusion, 75 mg/m2 BSA, on Day 1 of the 21-day cycles for up to 6 to 10 cycles, according to standard of care practices.

Other:
• placebo
matched to capivasertib appearance (2 tablets) BD given orally on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5, 9 to 12, and 16 to 19 in each week of a 21-day treatment cycle. Number of Cycles: until disease progression or unacceptable toxicity develops, death, or if the patient requests to stop the study treatment.

Drug:
• docetaxel
Patients will receive docetaxel in intravenous infusion, 75 mg/m2 BSA, on Day 1 of the 21-day cycles for up to 6 to 10 cycles, according to standard of care practices.

Locations

Country	Name	City	State
Australia	Research Site	Birtinya
Australia	Research Site	Greenslopes
Australia	Research Site	Kogarah
Australia	Research Site	Miranda
Australia	Research Site	North Adelaide
Australia	Research Site	Orange
Australia	Research Site	Redcliffe
Australia	Research Site	Wahroonga
Belgium	Research Site	Brasschaat
Belgium	Research Site	Gent
Belgium	Research Site	Liège
Belgium	Research Site	Wilrijk
Belgium	Research Site	Yvoir
Brazil	Research Site	Cachoeiro de Itapemirim
Brazil	Research Site	Ijuí
Brazil	Research Site	Itajai
Brazil	Research Site	Joinville
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Recife
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Rio De Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Salvador
Brazil	Research Site	Santa Maria
Brazil	Research Site	São José Do Rio Preto - SP
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Tres Lagoas
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Toronto
Canada	Research Site	Toronto	Ontario
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Temuco
Chile	Research Site	Vina del Mar
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Changsha
China	Research Site	Chengdu
China	Research Site	Chengdu
China	Research Site	Chongqing
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Hangzhou
China	Research Site	Harbin
China	Research Site	Jiaxing
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nantong
China	Research Site	Ningbo
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Yantai
China	Research Site	Zhengzhou
Czechia	Research Site	Horovice
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Pardubice
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 5
France	Research Site	Bordeaux
France	Research Site	Brest
France	Research Site	Clermont-Ferrand CEDEX 01
France	Research Site	Creteil
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Paris Cedex 05
France	Research Site	Rouen
France	Research Site	Saint Herblain Cedex
France	Research Site	Saint-Mande
France	Research Site	Strasbourg
France	Research Site	Strasbourg
France	Research Site	Vandoeuvre Les Nancy
France	Research Site	Villejuif Cedex
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Chaidari
Greece	Research Site	Marousi
Greece	Research Site	Patras
Greece	Research Site	Peiraias
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Kecskemét
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	Szeged
Hungary	Research Site	Szolnok
India	Research Site	Bikaner
India	Research Site	Meerut
India	Research Site	Mohali
India	Research Site	Nashik
India	Research Site	New Delhi
Israel	Research Site	Afula
Israel	Research Site	Be'er Ya'akov
Israel	Research Site	Beer Sheva
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Kfar Sava
Israel	Research Site	Petah Tikva
Israel	Research Site	Ramat Gan
Israel	Research Site	Tel Aviv
Japan	Research Site	Chiba-shi
Japan	Research Site	Hirakata-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kashihara-shi
Japan	Research Site	Kawagoe-shi
Japan	Research Site	Kita-gun
Japan	Research Site	Kobe-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Miyazaki-shi
Japan	Research Site	Nagano-Shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nakano-Ku
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Tsu-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Bukgu
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Cancún
Mexico	Research Site	Ciudad de México
Mexico	Research Site	Culiacan
Mexico	Research Site	Culiacán
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Oaxaca
Mexico	Research Site	Zapopan
Netherlands	Research Site	Den Haag
Netherlands	Research Site	Hoofddorp
Poland	Research Site	Konin
Poland	Research Site	Lodz
Poland	Research Site	Nowa Sol
Poland	Research Site	Opole
Poland	Research Site	Warszawa
Poland	Research Site	Wieliszew
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Lugo
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Sabadell
Spain	Research Site	Sevilla
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Edirne
Turkey	Research Site	Istambul
Turkey	Research Site	Izmir
Turkey	Research Site	Izmir
Turkey	Research Site	Sahinbey
Turkey	Research Site	Yüregir
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Guildford
United Kingdom	Research Site	Hackensack
United Kingdom	Research Site	Hampstead
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Southampton
United Kingdom	Research Site	Sutton
United States	Research Site	Albany	New York
United States	Research Site	Aurora	Colorado
United States	Research Site	Austin	Texas
United States	Research Site	Bala-Cynwyd	Pennsylvania
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Beverly Hills	California
United States	Research Site	Bronx	New York
United States	Research Site	Burlington	Vermont
United States	Research Site	Cerritos	California
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chesapeake	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago Ridge	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Fresno	California
United States	Research Site	Gilbert	Arizona
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	Kingwood	Texas
United States	Research Site	Lakewood	Colorado
United States	Research Site	Littleton	Colorado
United States	Research Site	Los Angeles	California
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Nashville	Tennessee
United States	Research Site	Orange City	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Sacramento	California
United States	Research Site	San Antonio	Texas
United States	Research Site	San Francisco	California
United States	Research Site	Santa Barbara	California
United States	Research Site	Santa Monica	California
United States	Research Site	Santa Rosa	California
United States	Research Site	Seattle	Washington
United States	Research Site	Watertown	South Dakota
United States	Research Site	White Plains	New York
United States	Research Site	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  France,  Greece,  Hungary,  India,  Israel,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Systolic and diastolic blood pressure	millimetre of mercury (mmHg)	Up to approximately 52 months
Other	Pulse rate (heart rate)	Beats per minute (BPM)	Up to approximately 52 months
Other	Body Temperature	Celsius (°C)	Up to approximately 52 months
Other	Weight	Kilograms (kg)	Up to approximately 52 months
Other	The number of participants with adverse events	Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with adverse events.	Up to approximately 52 months
Primary	Overall Survival (OS)	Overall survival is defined as time from randomisation until the date of death due to any cause.	up to approximately 52 months
Secondary	Radiographic Progression-free Survival (rPFS)	Radiographic Progression-free Survival (rPFS) is defined as time from randomization to radiographic progression as assessed by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) for soft tissue and/or Prostate Cancer Working Group 3 (PCWG3) for bone or death due to any cause	up to approximately 40 months
Secondary	Time to pain progression (TTPP)	Time to pain progression (TTPP) based on a 2-point increase from baseline in the Brief Pain Inventory-Short Form (BPI-SF) Item 3 'pain at its worse in the last 24 hours' score (scale from 0 ["no pain"] to 10 ["pain as bad as you can imagine"]) and/or initiation of/increase in opioid analgesic use.	up to approximately 40 months
Secondary	Time to first Symptomatic Skeletal-Related Event (SSRE)	SSRE 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; Occurrence of spinal cord compression; Orthopaedic surgical intervention for bone metastasis	up to approximately 52 months
Secondary	Time to deterioration in urinary symptoms (TTDUS)	Time to deterioration in urinary symptoms (TTDUS) is defined as time from randomization until the change from baseline reaches a clinically meaningful deterioration threshold using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Prostate Questionnaire Urinary Symptoms (QLQ-PR25 (US)) subscale score (EORTC IL166), where the question responses are provided on a numerical rating scale ranging from 1 ("not at all") to 4 ("very much").	up to approximately 40 months
Secondary	Time to deterioration in Physical Functioning (TTDPF)	Time to deterioration in Physical Functioning (TTDPF) is defined as the time from randomization until the change from baseline reaches a clinically meaningful deterioration threshold using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Physical Functioning (QLQ-C30 PF) subscale score (EORTC IL166), where the question responses are provided on a numerical rating scale ranging from 1 ("not at all") to 4 ("very much").	up to approximately 40 months
Secondary	Overall Pain Severity and Pain Interference as assessed by BPI-SF questionnaire	Change from baseline in Brief Pain Inventory-Short Form (BPI-SF) pain at its worse in the last 24 hours score (scale from 0 ["no pain"] to 10 ["pain as bad as you can imagine"]), pain severity (the mean of the four pain severity items each of which ranges from 0 ["no pain"] to 10 ["pain as bad as you can imagine"]) and interference domain scores (the mean of the seven pain interference items each of which ranges from 0 ["does not interfere"] to 10 ["completely interferes"]).	up to approximately 40 months
Secondary	Plasma concentration of capivasertib derived from a population PK model		pre dose (up to 90 minutes prior) and post dose (1 hour, 2 hours and 4 hours post dose)