A research study to compare the standard treatment and the study drug (degarelix) in combination with radiotherapy in patients with high-risk localized or locally-advanced cancer, who receive this treatment after initial radical prostatectomy or as primary therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Sep 2017 → ongoing

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ferring Pharmaceuticals A/S · European Organisation for Research and Treatment of Cancer (EORTC)

External identifiers

EU CT number

2024-513450-30-00

EudraCT number

2015-005098-19

ClinicalTrials.gov

NCT02799706

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response

To assess if GnRH antagonists improve PSA nadir within 6 months following completion of RT compared to GnRH agonists in combination with external beam radiation therapy in patients with high-risk localized or locally-advanced cancer, who receive this treatment as primary therapy.

Secondary objectives 3

1. Documentation of effect of GnRH antagonists on clinically significant cardiovascular events in the subgroup of patients at high risk of such events at baseline
2. Documentation of side effects and quality of life, I-PSS and urinary tract infections
3. Assessment of relative treatment effect on secondary efficacy endpoints (progression-free survival, clinical progression, time to next systemic therapy, time on therapy, overall and cancer specific survival) and on PSA at 6 months after end of RT

Conditions and MedDRA coding

very high risk localized or locally advanced prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patients may enter the trial in the clinical setting where a combination therapy involving irradiation combined with androgen deprivation therapy is envisaged.
2. For all patients: Magnesium and potassium within normal limits at the institution
3. For all patients: WHO Performance status 0-1
4. For all patients: Age ≥ 18 and ≤ 80 years
5. For all patients: Participants who have partners of childbearing potential must use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 3 months after last dose of study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly
6. For all patients: Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
7. For patients planned for primary radiotherapy: Histologically confirmed diagnosis of prostate adenocarcinoma diagnosed on a systematic ultrasound guided biopsy of the prostate containing at least 8 cores. An MRI-fusion biopsy is allowed if taken because a previous biopsy was negative. A TURP specimen pathology is allowed. Two of the following 4 risk factors for relapse: PSA ≥20 ng/ml; Gleason sum ≥8; cN1 (regional LN with a short axis length >10mm by CT scan or MRI) or pathologically confirmed lymph nodes (pN1); cT3-T4 (by MRI or core biopsy).
8. For all patients: Either of (1) M0 according to standard imaging methods (i.e. bone scan and conventional CT/MR image) or M0 according to modern imaging methods (i.e. whole-body MRI, PET/CT); (2) M0 according to bone scan and conventional CT/MR image and M1a and M1b only with ≤ 3 lesions detected by modern imaging methods are also allowed, called "Oligometastatic disease". Patients with oligometastatic disease will undergo metastasis targeted therapy.
9. For all patients: Testosterone ≥ 200 ng/dL
10. For all patients: Adequate bone marrow function (absolute neutrophil count (ANC) ≥ 1.5 109/L; hemoglobin ≥ 10.0 g/dl; platelets ≥ 100 109/L)
11. For all patients: Adequate hepatic function: (1) Bilirubin: total bilirubin ≤ 1.5 x upper limit of normal (ULN). (2) AST and/or ALT ≤ 2.5 x ULN.
12. For all patients: Adequate renal function: calculated creatinine clearance ≥ 50 mL/min

Exclusion criteria 11

1. M1c, confirmed by any imaging method or biopsy
2. Previous use of androgen deprivation therapy, antiandrogens if not interrupted for more than 6 months prior to entering the study
3. History of severe untreated asthma, anaphylactic reactions or severe urticaria and/or angiodema.
4. Hypersensitivity towards any of the active substances, the excipients used and synthetic GnRH or GnRH derivatives
5. No severe hepatic impairment (Child Pugh C)
6. Uncontrolled diabetes mellitus
7. Coronary revascularization (PCI or multivessel CABG), carotid artery or iliofemoral artery revascularizaton (percutaneous or surgical procedure) within the last 30 days prior to entering the trial
8. Certain risk factors for abnormal heart rhythms/QT prolongation: torsade de pointes ventricular arrhythmias (eg, heart failure, hypokalemia, or a family history of a long QT syndrome), a QT or corrected QT (QTc) interval >450 ms
9. Prior history of malignancies other than prostate adenocarcinoma (except patients with basal cell, squamous cell carcinoma of the skin), or the patient has been free of malignancy for a period of 3 years prior to first dose of study drug(s). Prior history of bladder cancer (except appropriately treated Tis or T1a) excludes the patient
10. Any contraindication to external beam radiotherapy
11. Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or any condition which, in the opinion of the investigator, would preclude participation in this trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the proportion of patients with PSA nadir < 0.1 ng/mL within 6 months following completion of RT.

Secondary endpoints 11

1. 1. Clinical progression-free survival
2. 2. Time to next systemic anticancer therapy
3. 3. Time to next systemic anticancer therapy other than ADT
4. 4. Proportion of patients switching from GnRH antagonists to GnRH agonists and total effective duration of treatment with the originally allocated drug.
5. 5. Overall survival
6. 6. Prostate Cancer specific survival
7. 7. PSA
8. 8. The incidence of clinical cardiovascular events – CCE (i.e. arterial embolic or thrombotic events, hemorrhagic or ischemic cerebrovascular conditions, myocardial infarction, and other ischemic heart disease) in patients who had cardiovascular events before entering the trial and in those without such events.
9. 9. The incidence of urinary tract infection
10. 10. Patient reported outcomes: (a) International Prostate Symptoms Score (I-PSS) (urinary symptoms); (b) Quality of Life (HRQoL) measured with EORTC QLQ-C30 and PR25 instruments with the overall health related quality of life scale as primary scale; (c) EQ-5L (to enable a future health economics analysis)
11. 11. Progression free survival defined as the time in days from randomization to death, clinical or biochemical progression or to the start of another line of systemic anti-neoplastic therapy in absence of progression or further systemic antineoplastic therapy, whichever comes first

Investigational products

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

Test 4

Comparator 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Sponsor organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Address

Emmanuel Mounierlaan 83 Bus 11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Contact name

Stéphanie Kromar

Public contact point

Organisation

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Contact name

Vassilis Golfinopoulos

Third parties 4

Locations

3 EU/EEA countries · 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 37 files

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

Application history

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