A phase II, randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist versus anti-androgen therapy (AAT) with apalutamide in patients with biochemical progression after radical prostatectomy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ziekenhuis Aan De Stroom

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

27 Jun 2024 → ongoing

Decision date (initial)

2024-06-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Johnson and Johnson

External identifiers

EU CT number

2024-512023-37-00

EudraCT number

2018-004365-13

ClinicalTrials.gov

NCT03899077

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare sexual function between the 2 treatment groups based on the EPIC-26 sexual domain at 9 months after start of hormonal treatment

Secondary objectives 5

1. To assess quality of life
2. To evaluate the toxicity and safety profile of apalutamide in combination with salvage radiotherapy
3. To evaluate the short-term efficacy of apalutamide in combination with salvage radiotherapy
4. To assess metastasis-free survival at 5 years
5. To evaluate radiotherapy quality assurance

Conditions and MedDRA coding

Prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Male, > 18 years old
2. ECOG 0-1
3. Histologically confirmed adenocarcinoma of the prostate
4. Previous radical prostatectomy (RP), pT2-3, pN0 or pNx
5. PSA detectable with confirmed rise (at least 2 weeks apart) at least 8 weeks after RP
6. Hormone-naive disease
7. Patients amendable to take oral medication
8. Hemoglobin ≥9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization
9. Platelet count ≥100,000 x 109/µL independent of transfusion and/or growth factors within 3 months prior to randomization
10. Serum albumin ≥3.0 g/dL
11. Serum creatinine <2.0 × upper limit of normal
12. Serum potassium ≥3.5 mmol/L
13. Serum total bilirubin ≤1.5 × ULN (note: in subjects with Gilbert’s syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
14. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN
15. Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry
16. Patient agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.
17. Patients who have received the information sheet and signed the informed consent form
18. Patients must be willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion criteria 6

1. Patients with severe erectile dysfunction according to international index of erectile function (IIEF-5) questionnaire (score 1-7)
2. Allergies, hypersensitivity or known intolerance to the study drugs or excipients.
3. History of any of the following: Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomization, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
4. History of any of the following: Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
5. Current evidence of uncontrolled hypertension or gastrointestinal disorder affecting absorption
6. Patients already included in another clinical trial involving an experimental drug.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EPIC-26 sexual domain score at 9 months after start of hormonal treatment (0 – 100 scale, with higher scores representing better sexual function)

Secondary endpoints 5

1. Quality of life will be assessed using EPIC-26 as well as the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C30 and PR25 as well as FACT-P
2. Acute as well as late toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (published November 27, 2017)
3. Regarding efficacy, prostate-specific antigen (PSA) response rates, defined as a decline from baseline in PSA level of 80% or greater, as well as PSA complete response rates, defined as a decline from baseline in PSA level of 90% or greater, will be prospectively collected at the 4 treatment visits (i.e. at 0, 3, 6, and 9 months)
4. Metastasis-free survival
5. Radiation therapy quality assurance

Investigational products

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

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ziekenhuis Aan De Stroom

Sponsor organisation

Ziekenhuis Aan De Stroom

Address

Kempenstraat 100

City

Antwerp

Postcode

2030

Country

Belgium

Scientific contact point

Organisation

Ziekenhuis Aan De Stroom

Contact name

Clinical Trials Office

Public contact point

Organisation

Ziekenhuis Aan De Stroom

Contact name

Clinical Trials Office

Locations

1 EU/EEA country · 7 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 8 files

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

Application history

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