Study with apalutamide in patients with prostate cancer in whom the prostate has been removed who are at high risk of disease recurrence

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaet Muenster

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Aug 2020 → ongoing

Decision date (initial)

2024-09-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511832-29-00

EudraCT number

2018-004329-10

ClinicalTrials.gov

NCT04295447

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine if adjuvant apalutamide in prostate cancer patients at high risk of developing subsequent metastatic disease results in prolonged biochemically recurrence-free survival after radical prostatectomy (RPE)
in comparison to standard of care (SOC).

Secondary objectives 2

1. To characterize the safety and tolerability of apalutamide in subjects with high-risk, localized or locally advanced prostate cancer having received RPE
2. To determine if apalutamide in subjects with high-risk, localized or locally advanced prostate cancer having received RPE results in an improvement of PSADT, i.e. increased PSADT in case of BCR

Conditions and MedDRA coding

High risk adenocarcinoma of the prostate after radical prostatectomy (RPE)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Signed informed consent form (ICF)
2. Men ≥ 18 years of age
3. Patients with histologically confirmed adenocarcinoma of the prostate after radical prostatectomy
4. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
5. Exclusion of metastatic disease by CT-scan of abdomen (MRI of abdomen is possible) and bone scan prior to study inclusion. A PSMA PET-CT/MRI is possible. In this case it has to be done with a diagnostic CT/MRI with contrast media and not with a low dose CT-scan only. In case PSMA-PET imaging has been done, a bone scan can be omitted. CT/MRI, and bone-scan imaging or PSMA PET-CT/MRI administered ≤12 weeks before RPE may be used for screening
6. Patients after RPE must meet the d'Amico criteria for high risk of disease recurrence (T-stage and Gleason-score determined after radical prostatectomy) i.e. 1 of the following after RPE: 1) Gleason score ≥8, any T-stage, any iPSA or 2) Gleason score 6 or 7, any iPSA and ≥pT3 or 3) iPSA >20 ng/ml, any Gleason score, any T-stage.
7. Patients have to have recovered from radical prostatectomy within eight weeks to be able to take part in the study
8. PSA must have declined below 0.2 ng/ml prior to randomization
9. Adequate hematologic, hepatic, and renal function: • Hematologic i) Haemoglobin ≥ 9.0 g/dL independent of transfusions ii) Neutrophils ≥ 1.5 Ths./μL • Hepatic i) Total Bilirubin =< 1.5X upper limit of normal (ULN) [except for subjects with documented Gilbert's disease in which case total bilirubin not to exceed 10X ULN] ii) Alanine (ALT) and aspartate (AST) aminotransferase =< 2.5X ULN • Renal: i) Serum creatinine <1.5X ULN or calculated creatinine clearance ≥ 50 mL/min ii) Serum potassium ≥ 3.5 mM iii) Serum albumin ≥ 3.0 g/dL
10. Ability to swallow study medication tablets
11. In case of apalutamide treatment: Agrees to use a condom and another highly effective method of birth control if he is having sex with a woman of childbearing potential or to use a condom if he is having sex with a woman who is pregnant

Exclusion criteria 25

1. Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone q.d.
2. Prior cytotoxic chemotherapy or biologic therapy for the treatment of prostate cancer
3. Prior or current treatment of prostate cancer with apalutamide, enzalutamide, darolutamide, or other investigational agents targeting the androgen receptor
4. Prior therapy with Sipuleucel-T or other vaccination or immunogenic therapy for the treatment of prostate cancer
5. Prior treatment with abiraterone acetate or other androgen synthesis inhibitors (e. g. ketoconazole, TAK700, TOK001)
6. Use of 5-α reductase inhibitors (eg, dutasteride, finasteride) ≤4 weeks prior to randomization
7. Prior surgical castration or medical castration using LHRH-Agonists or GnRH-Antagonists
8. Prior or current radiation or radionuclide (including radium-223 dichloride) therapy for treatment of prostate cancer (adjuvant radiation of the prostate bed without involvement of the regional lymph node template as by standard of care in case of positive surgical margins (R1) is allowed)
9. Prior or current systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
10. Any lymph node or distant metastasis
11. History of seizures or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness ≤1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect).
12. Current or prior treatment with anti-epileptic medications for the treatment of seizures
13. Management of cardiovascular risk factors, such as hypertension, diabetes or dyslipidaemia should be optimised as per standard of care before treatment with apalutamide will be initiated 13.1. Uncontrolled hypertension (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg. For patients with relevant comorbidities (e.g. diabetes) systolic BP ≥130 mmHg or diastolic BP ≥80 mmHg). Patients with a history of hypertension are allowed provided that blood pressure is controlled by anti-hypertensive treatment 13.2. Patients with uncontrolled diabetes defined as HbA1c ≥7.5% 13.3. Patients with a dyslipidemia defined as LDL cholesterol >100 mg/dl. For patients with a dyslipidemia defined as LDL cholesterol >100 mg/dl and SCORE-value of 1-5%: In case of a SCORE-value of <1% a LDL cholesterol level of up to 115 mg/dl is acceptable. In case of increased LDL cholesterol above these values a statin-therapy can be initiated and a rescreening within 4 weeks is possible 13.4. Cardiovascular risk assessment via an appropriate score (e.g. the SCORE-Chart for the European high/low risk score from the European Society of Cardiology) and ≥ borderline risk i.e. 10% of developing cardiovascular events within 10 years without prior cardiovascular disease
14. Active or symptomatic viral hepatitis or chronic liver disease or HIV
15. History of pituitary or adrenal dysfunction
16. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 12 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50% at baseline, or clinically relevant pelvic lymphocele after radical prostatectomy as evaluated by clinical examination and/or pelvic ultrasound (if a risk is present, patients may be allowed to be enrolled after adaptive risk management).
17. Any condition that requires treatment with digoxin, digitoxin, and other digitalis drugs
18. Long QT Syndrome
19. Atrial Fibrillation, or other cardiac arrhythmia requiring therapy
20. Other malignancy with a ≥30% probability of recurrence within 24 months, except non-melanoma skin cancer
21. Any condition, which, in the opinion of the investigator, would preclude participation in this trial.
22. Gastrointestinal conditions affecting absorption
23. Hypersensitivity to the active substance, or to any of the excipients of the study medication
24. Any psychological, cognitive, familial, sociological or geographical condition that, in the investigator's opinion, compromises the patient's ability to understand the patient information, to give informed consent or to comply with the study protocol.
25. Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial. There may be exceptions at the discretion of the (coordinating) investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS). This endpoint is defined as time interval from randomization until BCR, metastases, or death from any cause, whichever occurs first.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaet Muenster

Sponsor organisation

Universitaet Muenster

Address

Schlossplatz 2, Schlossbezirk Schlossbezirk

City

Muenster

Postcode

48149

Country

Germany

Scientific contact point

Organisation

Universitaet Muenster

Contact name

Klinik für Urologie und Kinderurologie am UKM Münster

Public contact point

Organisation

Universitaet Muenster

Contact name

Klinik für Urologie und Kinderurologie am UKM Münster

Third parties 2

Locations

2 EU/EEA countries · 15 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 12 files

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

Application history

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