A trial to learn how well capivasertib with docetaxel works and how safe it is in people with metastatic castration-resistant prostate cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Jul 2022 → ongoing

Decision date (initial)

2024-08-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca KK, Japan · AstraZeneca AB, Sweden

External identifiers

EU CT number

2023-504996-26-00

EudraCT number

2021-005201-27

ClinicalTrials.gov

NCT05348577

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Efficacy, Therapy, Pharmacokinetic

To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of overall survival (OS) in patients with mCRPC in the overall population.

To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of radiographic progression free survival (rPFS) in patients with mCRPC in the overall population.

Secondary objectives 3

1. To demonstrate superiority of capivasertib + docetaxel relative to placebo + docetaxel by assessment of: - OS in patients with mCRPC and PTEN- proficient tumours (IHC) - OS in patients with mCRPC and PTEN-deficient tumours (IHC) - time to pain progression (TTPP) - time to first Symptomatic Skeletal- Related Event (SSRE) in the overall population
2. To demonstrate effectiveness of capivasertib + docetaxel relative to placebo + docetaxel by assessment of: - rPFS in patients with mCRPC and PTEN-proficient tumours (IHC) - rPFS in patients with mCRPC and PTEN-deficient tumours (IHC) - time to deterioration in urinary symptoms (TTDUS) - time to deterioration in Physical Functioning (TTDPF) - Health-related quality of life (HrQoL) using the BPI-SF in the overall population
3. To evaluate the PK of capivasertib in combination with docetaxel in the overall population.

Conditions and MedDRA coding

Metastatic Castration Resistant Prostate Cancer (mCRPC)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Histologically-confirmed prostate adenocarcinoma without predominant neuroendocrine or small cell cancers
2. 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)
3. 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
4. Evidence of mCRPC with progression of disease despite androgen deprivation therapy (ADT)
5. Serum testosterone level ≤ 50 ng/dL
6. Candidate for docetaxel and steroid therapy
7. Ongoing ADT with LHRH agonist, LHRH antagonist, or bilateral orchiectomy
8. Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1 and anticipated minimum life expectancy of 12 weeks
9. 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
10. Able and willing to swallow and retain oral medication
11. Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion criteria 15

1. Radiotherapy with a wide field of radiation within4 weeks before start of study treatment
2. Major surgery (excl. placement of vascular access, transurethral resection of prostate, bilateral orchiectomy, internal stents) within 4 weeks of start of study treatment
3. 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)
4. Any of the following cardiac criteria i. Mean resting correctedQT 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 bloodpressure < 90mmHg and/or diastolic bloodpressure < 50mmHg vi. Haemodynamic instability
5. Clinically significant abnormalities of glucose metabolism as defined by any of the following i. Patients with diabetes mellitus (DM) type1 or DM type 2 requiring insulin treatment ii. HbA1c ≥ 8.0% (63.9 mmol/mol)
6. Inadequate bone marrow reserve or organ function as demonstrated by laboratory values as specified in the protocol
7. 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), that makes it undesirable for the patient to participate in the study or that would jeopardise compliance with the protocol
8. Known to have active hepatitis B or C infection; HIV with a detectable viral RNA or a CD4+ T-cell count < 350 cells/uL or a history of an AIDS defining opportunistic infection within the past 12 months
9. 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
10. Any other disease, 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
11. Previous allogeneic bone marrow transplant or solid organ transplant
12. 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
13. 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)
14. 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 iv.Any other immunotherapy, immunosuppressant medication (other than corticosteroids) or anticancer agents (except ADT )within 3weeks of the first dose of study treatment v. Strong inhibitors or strong inducers of cytochrome P450 (CYP) 3A4 within2 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 the study treatment, during,and for at least 90 days after the last dose of the study treatment
15. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall survival is defined as time from randomisation until the date of death due to any cause. The comparison will include all randomised patients as randomised, regardless of whether the patient withdraws from therapy or receives another anticancer therapy.
2. Radiographic Progression-free Survival (rPFS) 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 8

1. OS is defined as time from randomisation until the date of death due to any cause.
2. Radiographic Progression-free Survival (rPFS) 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
3. Time to pain progression (TTPP) based 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 opioid analgesic use
4. Time to start Symptomatic Skeletal-Related Event (SSRE)
5. Time to deterioration in urinary symptoms (TTDUS), change from baseline that reaches a clinically meaningful deterioration threshold.
6. Time to deterioration in Physical Functioning (TTDPF), change from baseline that reaches a clinically meaningful deterioration threshold.
7. Change from baseline in BPI-SF worst pain score, pain severity and interference domain scores.
8. Plasma concentration of capivasertib derived from a population PK model

Investigational products

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

Test 5

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

Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Information Center

Third parties 3

Locations

8 EU/EEA countries · 57 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 70 files

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

Application history

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