Capivasertib + Abiraterone as Treatment for Patients with Metastatic Hormone-sensitive Prostate Cancer Characterised by PTEN deficiency (CAPItello-281)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Phenomena and Processes [G] - Reproductive and Urinary Physiological Phenomena [G08], Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11], Phenomena and Processes [G] - Digestive System and Oral Physiological Phenomena [G10], Phenomena and Processes [G] - Physiological processes [G07], Phenomena and Processes [G] - Circulatory and Respiratory Physiological Phenomena [G09], Phenomena and Processes [G] - Microbiological Phenomena [G06], Phenomena and Processes [G] - Genetic Phenomena [G05], Phenomena and Processes [G] - Cell Physiological Phenomena [G04]

Trial duration

18 Sep 2020 → ongoing

Decision date (initial)

2024-06-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AstraZeneca AB · Astrazeneca K.K.

External identifiers

EU CT number

2023-504998-20-00

EudraCT number

2020-000346-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacodynamic

To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone assessment by the investigator of radiographic progression-free survival (rPFS) in patients with PTEN-deficient mHSPC

Secondary objectives 1

1. 1.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of overall survival 2.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to start of first subsequent therapy or death (TFST) 3.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to start symptomatic skeletal event-free survival (SSE-FS) 4.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to pain progression (TTPP) 5.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to PSA progression 6.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of progression-free survival after next-line treatment (PFS2) 7.To evaluate the PK of capivasertib in combination with abiraterone

Conditions and MedDRA coding

Metastatic Hormone-sensitive Prostate Cancer Characterised by PTEN deficiency

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002551-PIP01-18

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Asymptomatic or mildly symptomatic, histologically-confirmed de novo metastatic hormone-sensitive prostate adenocarcinoma without small cell tumours 2. Consent to provide a FFPE tissue block (preferred) or slides. Tissue from bone metastases is not acceptable 3. A valid PTEN IHC result indicating PTEN deficiency (centralized testing) 4. 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 5. Candidate for abiraterone and steroid therapy 6. Ongoing ADT with GnRH analogue, or LHRH agonists or antagonist, or bilateral orchiectomy 7. 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 8. Able and willing to swallow and retain oral medication 9. 7 day Brief Pain Inventory-Short Form (BPI-SF) and Brief Fatigue Inventory(BFI) questionnaires and the analgesic diary during screening completed 10. Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion criteria 2

1. 1.Prior radical prostatectomy or definitive radiotherapy (RT) with therapeutic intent for prostate cancer. Palliative RT is allowed within 4 wks before start of study 2.Major surgery within 4 wks of start of study 3.Brain metastases, or spinal cord compression (unless asymptomatic, treated and stable 4 Past medical history or evidence of ongoing interstitial lung disease or radiation pneumonitis requiring steroids 5.Any of the following cardiac criteria: -Mean resting QTc >470 msec -History of QT prolongation associated with other medications that required discontinuation - Family history of long QT syndrome or unexplained sudden death under the age of 40 - Medical history significant for arrhythmia, symptomatic or requiring treatment; symptomatic or uncontrolled atrial fibrillation; or asymptomatic sustained ventricular tachycardia - Any clinically important abnormalities of resting ECG - Factors that increase the risk of QTc prolongation or of arrhythmic events, or any concomitant medication known to significantly prolong the QT interval and associated with Torsade de Pointes - Experience of any of the following in the preceding 3 months: coronary artery bypass graft, angioplasty, myocardial infarction or unstable angina pectoris - Congestive heart failure NYHA Grade ≥2 - Symptomatic hypotension (SBP<90 mmHg and/or DBP<50mmHg)or uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥95 mmHg) 6. Any of following clinically significant abnormalities of glucose metabolism: - Patients with diabetes mellitus type 1 or 2 requiring insulin - HbA1c ≥8.0% (63.9 mmol/mol) 7. Inadequate bone marrow reserve or organ function: - Neutrophils <1.5x109/L - Platelets <100x109/L - Hb <9g/dL (<5.59 mmol/L) - ALT and AST >2.5x ULN if no liver metastases or >5x ULN if liver metastases - Bilirubin >1.5x ULN - CrCL <50 mL/min 8. Severe or uncontrolled systemic diseases, including active bleeding diatheses, active infection including hepatitis B and C. diagnosis with HIV or a history of an AIDS opportunistic infection within the past 12 months 9. Unevaluable for both bone and soft tissue progression as defined by the following : bone "superscan" and no soft tissue lesion evaluable by RECIST 10.Conditions that would preclude adequate absorption of capivasertib
2. 11. Any other clinical finding that, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug 12. Evidence of dementia, altered mental status, or any psychiatric condition prohibiting understanding or rendering of informed consent 13. Previous allogeneic bone marrow or solid organ transplant 14. History of another primary malignancy except for malignancy treated with curative intent with no known disease ≥ 2 years before starting study and of low recurrence risk 15. Following treatments: - Nitrosourea or mitomycin C within 6 wks of the start of study - Any other anticancer therapy or immunosuppressant medication (other than corticosteroids) within 3 wks of the start of study - Strong inhibitors or inducers of CYP3A4 within 2 wks before the start of study - Drugs known to prolong the QT interval and associated with torsades de pointes within 5 T½of the start of the study 16. Participation in another clinical study with an investigational product administered in the last 30 days or 5 half-lives whichever is longer 17. History of hypersensitivity to active or inactive excipients of capivasertib, abiraterone, or drugs with a similar chemical structure or class 18. Involvement in the planning and/or conduct of the study 19. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study requirements 20. Any restriction or contraindication based on the local prescribing information that would prohibit the use of abiraterone

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1.Radiographic Progression-free Survival (rPFS) in patients with PTENdeficient 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 as Assessed by the Investigator

Secondary endpoints 3

1. 1.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of overall survival 2.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to start of first subsequent therapy or death (TFST)
2. 3.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to start symptomatic skeletal event-free survival (SSE-FS) 4.To compare the effect of capivasertib+abiraterone relative to placebo+abiraterone by assessment of time to pain progression (TTPP)
3. 5.To evaluate the PK of capivasertib in combination with abiraterone 6.To evaluate safety and tolerability assessment of capivasertib+abiraterone as compared to placebo+abiraterone in patients with PTEN-deficient mHSPC

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

9 EU/EEA countries · 65 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 82 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications