Informations générales (source: ClinicalTrials.gov)
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide Plus Androgen Deprivation Therapy (ADT) Compared With Placebo Plus ADT in Patients With High-risk Biochemical Recurrence (BCR) of Prostate Cancer (ARASTEP)
Interventional
Phase 3
Bayer (Voir sur ClinicalTrials)
avril 2023
février 2029
17 décembre 2024
Researchers are looking for a better way to treat men at high-risk of biochemical
recurrence (BCR) of prostate cancer.
BCR means that in men who had prostate cancer and were treated by either surgery and/ or
radiation therapy, the blood level of a specific protein called PSA rises. PSA is a
marker of prostate cancer cells activity. The PSA increase means that the cancer has come
back even though conventional imaging such as computed tomography (CT) scans, magnetic
resonance imaging (MRI) and bone scans does not show any lesion of prostate cancer.
Recently a more sensitive imaging method called prostate-specific membrane antigen [PSMA]
positron emission tomography [PET]) /computed tomography [CT]) scan may identify prostate
cancer lesions not detectable by conventional imaging. Men with BCR have a higher risk of
their cancer spreading to other parts of the body, particularly when PSA levels raised to
a certain limit within a short period of time after local therapies. Once the cancer
spreads to other parts of the body, it can become even harder to treat.
In men with prostate cancer, male sex hormones (also called androgens) like testosterone
can help the cancer grow and spread. To reduce androgens levels in these patients, there
are treatments that block androgens production in the body called androgen deprivation
therapy (ADT). ADT is often used to stop prostate cancer. Another way to stop prostate
cancer growth and spread is to block the action of androgen receptors on prostate cancer
cells called androgen receptor inhibitors (ARIs). The new generation ARIs including
darolutamide can block the action of androgens receptors and are available for the
treatment of prostate cancer in addition to ADT. It is already known that men with
prostate cancer benefit from these treatments.
The main objective of this study is to learn if the combination of darolutamide and ADT
prolongs the time that the participants live without their cancer getting worse, or to
death due to any cause, compared to placebo (which is a treatment that looks like a
medicine but does not have any medicine in it) and ADT given for a pre-specified duration
of 24 months.
To do this, the study team will measure the time from the date of treatment allocation to
the finding of new cancer spread in the participants by using PSMA PET/CT, or death due
to any cause. The PSMA PET/CT scans is performed using a radioactive substance called a
"tracer" that specifically binds to the prostate-specific membrane antigen (PSMA) which
is a protein often found in large amounts on prostate cancer cells.
To avoid bias in treatment, the study participants will be randomly (by chance) allocated
to one of two treatment groups. Based on the allocated treatment group, the participants
will either take darolutamide plus ADT or placebo plus ADT twice daily as tablets by
mouth. The study will consist of a test (screening) phase, a treatment phase and a
follow-up phase. The treatment duration is pre-specified to be 24 months unless the
cancer gets worse, the participants have medical problems, or they leave the study for
any reason. In addition, image guided radiotherapy (IGRT) or surgery is allowed and your
doctor will explain the benefits and risks of this type of therapy.
During the study, the study team will:
- take blood and urine samples.
- measure PSA and testosterone levels in the blood samples
- do physical examinations
- check the participants' overall health
- examine heart health using electrocardiogram (ECG)
- check vital signs
- check cancer status using PSMA PET/CT scans, CT, MRI and bone scans
- take tumor samples (if required)
- ask the participants if they have medical problems
About 30 days after the participants have taken their last treatment, the study doctors
and their team will check the participants' health and if their cancer worsened. The
study team will continue to check this and regularly ask the participants questions about
medical problems and subsequent therapies until they leave the study for any reason or
until they leave the study for any reason or until the end of the study, whatever comes
first.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/12/2024 12:44:13 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Pierre BLANCHARD | 15/04/2024 14:34:09 | Contacter | ||
| CLCC RENE HUGUENIN INSTITUT CURIE | 04/12/2024 12:44:01 | Contact (sur clinicalTrials) | |||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Bichat | Contact (sur clinicalTrials) | ||||
| AP-HP - Hôpital Henri Mondor-Albert Chenevier | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Bourgogne - Hôpital Privé Le Bois - 59000 - Lille - France | Contact (sur clinicalTrials) | ||||
| Centre d'oncologie du Pays Basque - 64100 - Bayonne - France | Contact (sur clinicalTrials) | ||||
| Centre Georges Francois Leclerc Dijon - 21079 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Lyon Sud - 69495 - Pierre Benite - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Regional et Universitaire (CHRU) de Besancon - L'Hopital Jean Minjoz - 25000 - Besancon - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Regional Universitaire (CHRU) Brest - Hopital de la Cavale Blanche - 29609 - Brest - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Universitaire de Clermont Ferrand - Gabriel Montpied - 63003 - Clermont Ferrand - France | Contact (sur clinicalTrials) | ||||
| CHU GRENOBLE - Hopital Michallon - 38043 - Grenoble - Grenoble Cedex 9 - France | Contact (sur clinicalTrials) | ||||
| Clinique Clementville - 34070 - Montpellier - France | Contact (sur clinicalTrials) | ||||
| Hôpital Bretonneau - 37044 - Tours - France | Contact (sur clinicalTrials) | ||||
| Hôpital Claude Huriez - Lille - 59037 - Lille - France | Contact (sur clinicalTrials) | ||||
| Hôpital de la Timone - Marseille - 13005 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Hôpital Pellegrin - Bordeaux - 33076 - BORDEAUX cedex - France | Contact (sur clinicalTrials) | ||||
| Hôpital Pontchaillou - 35033 - Rennes Cedex - France | Contact (sur clinicalTrials) | ||||
| ICANS - Institut de Cancérologie de Strasbourg Europe - 67033 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Institut Claudius Regaud - iUCT Oncopole - 31059 - Toulouse Cedex 9 - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de Bourgogne - 21000 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de Lorraine - Alexis Vautrin - 54519 - Vandoeuvre-les-Nancy - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie de l'Ouest - Saint Herblain - 44800 - Saint-Herblain - France | Contact (sur clinicalTrials) | ||||
| Institut de Cancérologie Jean Godinot - 51726 - Reims - France | Contact (sur clinicalTrials) | ||||
| UNICANCER - Centre Leon-Berard (CLB) - 69008 - Lyon - France | Contact (sur clinicalTrials) | ||||
Critères
Homme
Inclusion Criteria:
- Capable of giving signed informed consent as described which includes compliance
with the requirements, restrictions listed in the informed consent form (ICF), and
in this protocol.
- Male ≥18 years of age at the time of signing the informed consent.
- Histologically or cytologically confirmed adenocarcinoma of prostate.
- Prostate cancer initially treated by: radical prostatectomy (RP) followed by
adjuvant radiotherapy (ART), or salvage radiotherapy (SRT), or RP in participants
who are unfit for (or refused) ART or SRT, or primary radiotherapy (RT).
- High-risk biochemical recurrence (BCR), defined as Prostate-specific antigen
doubling time (PSADT) <12 months calculated using the formula provided by the
Sponsor, and PSA ≥0.2 ng/mL after ART or SRT post RP or after RP in participants who
are unfit for ART or SRT (local or central values accepted), or PSA ≥2 ng/mL above
the nadir after primary RT only (local or central values accepted).
- Participants must undergo prostate-specific membrane antigen positron emission
tomography/computed tomography (PSMA PET/CT) within the 42-day Screening period
using either 18F-DCFPyL (piflufolastat F 18) or 68Ga-PSMA-11 which will be assessed
by blinded independent central review (BICR) to identify at least one PSMA PET/CT
lesion of prostate cancer.
- Serum testosterone ≥150 ng/dL (5.2 nmol/L) (local assessment is allowed whenever
central assessment cannot be done).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Blood counts at screening: Hemoglobin ≥9.0 g/dL (participant must not have received
blood transfusion within 7 days prior to sample being taken); Absolute neutrophil
count (ANC) ≥1.5x10^9/L (participant must not have received any growth factor within
4 weeks prior to sample being taken); Platelet count ≥100x10^9/L.
- Screening values of: Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal
(ULN); Aspartate aminotransferase (AST) ≤1.5 x ULN; Total bilirubin (TBL) ≤1.5 ULN,
(except participants with a diagnosis of Gilbert's disease); Estimated glomerular
filtration rate (eGFR) >40 ml/min/1.73 m^2 calculated by the CKD-EPI formula.
- Sexually active male participants must agree to use contraception as detailed in the
protocol during the Treatment period and for at least 1 week after the last dose of
study treatment, and refrain from donating sperm during this period.
- Capable of giving signed informed consent as described which includes compliance
with the requirements, restrictions listed in the informed consent form (ICF), and
in this protocol.
- Male ≥18 years of age at the time of signing the informed consent.
- Histologically or cytologically confirmed adenocarcinoma of prostate.
- Prostate cancer initially treated by: radical prostatectomy (RP) followed by
adjuvant radiotherapy (ART), or salvage radiotherapy (SRT), or RP in participants
who are unfit for (or refused) ART or SRT, or primary radiotherapy (RT).
- High-risk biochemical recurrence (BCR), defined as Prostate-specific antigen
doubling time (PSADT) <12 months calculated using the formula provided by the
Sponsor, and PSA ≥0.2 ng/mL after ART or SRT post RP or after RP in participants who
are unfit for ART or SRT (local or central values accepted), or PSA ≥2 ng/mL above
the nadir after primary RT only (local or central values accepted).
- Participants must undergo prostate-specific membrane antigen positron emission
tomography/computed tomography (PSMA PET/CT) within the 42-day Screening period
using either 18F-DCFPyL (piflufolastat F 18) or 68Ga-PSMA-11 which will be assessed
by blinded independent central review (BICR) to identify at least one PSMA PET/CT
lesion of prostate cancer.
- Serum testosterone ≥150 ng/dL (5.2 nmol/L) (local assessment is allowed whenever
central assessment cannot be done).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Blood counts at screening: Hemoglobin ≥9.0 g/dL (participant must not have received
blood transfusion within 7 days prior to sample being taken); Absolute neutrophil
count (ANC) ≥1.5x10^9/L (participant must not have received any growth factor within
4 weeks prior to sample being taken); Platelet count ≥100x10^9/L.
- Screening values of: Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal
(ULN); Aspartate aminotransferase (AST) ≤1.5 x ULN; Total bilirubin (TBL) ≤1.5 ULN,
(except participants with a diagnosis of Gilbert's disease); Estimated glomerular
filtration rate (eGFR) >40 ml/min/1.73 m^2 calculated by the CKD-EPI formula.
- Sexually active male participants must agree to use contraception as detailed in the
protocol during the Treatment period and for at least 1 week after the last dose of
study treatment, and refrain from donating sperm during this period.
- Pathological finding consistent with small cell, ductal or ≥50 % component of
neuroendocrine carcinoma of the prostate.
- History of bilateral orchiectomy.
- Metastases or recurrent /new malignant lesions in prostate gland/bed seminal
vesicles, lymph nodes below the CIA bifurcation on conventional imaging (CI) as
assessed by BICR during screening.
- Brain metastasis on PSMA PET /CT by BICR at screening.
- High-risk BCR after primary radiotherapy with new loco-regional lesions on screening
PSMA PET/CT who are eligible for curative salvage prostatectomy.
Note: Participants treated with curative salvage prostatectomy after primary RT who meet
the PSA criteria (inclusion criteria 5) may be considered for the study.
- Prior treatment with second generation (e.g. enzalutamide, apalutamide) androgen
receptor inhibitors (ARIs) and CYP 17 inhibitors (e.g., abiraterone) within 18
months prior to signing of the ICF.
- Prior treatments with PSMA-radiotherapeutics within 12 months prior to
randomization.
- Prior radiotherapy (including image-guided radiotherapy) as primary, adjuvant or
salvage treatment completed within 8 weeks prior to signing of the ICF.
- Any prior malignancy (other than adequately treated basal cell or squamous cell skin
cancer, superficial bladder cancer, or any other cancer in situ currently in
complete remission) within 5 years.
- History of pelvic radiotherapy for other malignancy.