Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer

  • STATUS
    Recruiting
  • End date
    Jun 23, 2024
  • participants needed
    885
  • sponsor
    European Organisation for Research and Treatment of Cancer - EORTC
Updated on 23 January 2021
ct scan
gonadotropin
androgens
testosterone
androgen suppression
luteinizing hormone-releasing hormone agonist
degarelix
external beam radiation therapy
adenocarcinoma
adenocarcinoma of prostate
gonadorelin
immunological adjuvant

Summary

The primary objective of the trial is to assess if GnRH antagonists in combination with external beam radiation therapy improve progression free survival (progression that can be biological, clinical, or death) compared to GnRH agonists in combination with external beam radiation therapy.

Secondary objectives include:

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

Description

Phase IIIb randomized stratified open-label comparative 2-arm superiority study with a pre-set non-inferiority boundary.

Registered GnRH antagonists, degarelix, will be given at the dose of 240 mg given as two subcutaneous injections of 120 mg at a concentration of 40 mg/mL on day 1, followed by 80 mg given as one subcutaneous injection at a concentration of 20 mg/mL every 28 days (2 days).

External beam radiotherapy (EBRT) to a total dose of 78-80 Gy, delivered as one daily fraction, five days a week, started between d1 and months 6 of the androgen deprivation therapy as per institution policy. The irradiation is the same as in the reference therapy arm.

The minimum duration of androgen deprivation with GnRH agonist or antagonist therapy is 18 months.

For each patient, the duration of therapy must be elected upfront by the treating physician among three possible options: 18, 24 or 36 months. The institution shall also declare upfront the duration of the neoadjuvant treatment they intend to deliver to each patient (between 0 and 6 months).

The primary endpoint is progression-free survival defined as the time in days from randomization to death, clinical or biochemical progression, whichever comes first.

Where

  • PSA progression based on Phoenix definition, i.e. a rise by 2 ng/mL or more above the nadir PSA (Ref. 17) confirmed by a second value measured minimum 3 months later
  • Clinical progression is defined as onset of obstructive symptoms requiring local treatment and demonstrated to be caused by cancer progression or evidence of metastases detected by clinical symptoms and confirmed by imaging
  • Start of another line of systemic therapy in absence of progression
  • Death due to any cause

Secondary endpoints:

  • Clinical progression-free survival
  • Time to next systemic anticancer therapy (including secondary hormonal manipulation)
  • Proportion of patients switching from GnRH antagonists to GnRH agonists and total effective duration of treatment with the originally allocated drug.
  • Overall survival
  • Cancer specific survival
  • PSA at six months after completion of RT Safety will be scored by the CTCAE version 4.0. The major safety endpoints in this study are
  • 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.
  • Incidence of urinary tract infection

Details
Condition Malignant neoplasm of prostate, Prostatic disorder, Prostate Disorders, Prostate Cancer, Early, Recurrent, Prostate Cancer, prostate carcinoma, prostate cancers
Treatment Radiotherapy, Degarelix, approved GnRH agonist
Clinical Study IdentifierNCT02799706
SponsorEuropean Organisation for Research and Treatment of Cancer - EORTC
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 80 yrs?
Are you male?
Do you have Malignant neoplasm of prostate?
Do you have any of these conditions: Prostatic disorder or Prostate Disorders or Malignant neoplasm of prostate or prostate carcinoma or Prostate Cancer or prostate cancers or Prostate Ca...?
Histologically confirmed diagnosis of prostate adenocarcinoma
PSA 10 ng/ml and two of the following 4 criteria
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) (i.e. If PSA 20 ng/ml then only one of the other 3 risk factors is needed)
M0 by standard imaging work-up (see chapter [6.1.1.1](telnet://6.1.1.1))
Testosterone 200 ng/dl
Adequate renal function: calculated creatinine clearance 50 mL/min (Appendix D) Magnesium and potassium within normal limits of the institution or corrected to within normal limits prior to the first dose of treatment
Patients with prolonged QT-intervals due to prescribed Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic medication must be carefully evaluated for GnRH-agonist or GnRH antagonist use, because these drugs may prolong the QT-interval
WHO Performance status 0-1
Age 18 and 80 years
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
Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion Criteria

Previous use of androgen deprivation therapy (ADT), antiandrogens. 5-alpha reductase inhibitors are allowed if interrupted for more than 6 months prior to entering the study
History of severe untreated asthma, anaphylactic reactions or severe urticaria and/or angioedema
Hypersensitivity towards the investigational drug
The following biological parameters :AST, ALT, total bilirubin, prothrombin time, serum albumin above upper level of normal range No severe hepatic impairment (Child Pugh C)
History of gastro-intestinal disorders (medical disorder or extensive surgery) that may interfere with the absorption of the protocol treatment
History of pituitary or adrenal dysfunction
Uncontrolled diabetes mellitus
History of ulcerative colitis, Crohn's Disease, ataxia, telangiectasia, systemic lupus erythematous, or Fanconi anemia
Clinically significant heart disease as evidence myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class III or IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline
Coronary revascularization (PCI or multivessel CABG), carotid artery or iliofemoral artery revascularization (percutaneous or surgical procedure) within the last 30 days prior to entering the trial
Certain risk factors for abnormal heart rhythms/QT prolongation: torsade de pointes ventricular arrhythmias (e.g, heart failure, hypokalemia, or a family history of a long QT syndrome), a QT or corrected QT (QTc) interval >450 ms at baseline, or intake of medications that prolong the QT/QTc interval
Uncontrolled hypertension (systolic BP 160 mmHg or diastolic BP 95 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
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 excludes the patient
Prior radical prostatectomy (TURP or suprapubic adenomectomy for benign prostatic hyperplasia is allowed)
Prior brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields
Any contraindication to external beam radiotherapy
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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note