A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) With ADT in Men With Hormone Sensitive Prostate Cancer and Raise of Prostate Specific Antigen (PSA) Levels After Local Therapies (ARASTEP)

Overview

About this study

The purpose of this study is to determine if darolutamide plus ADT given for 12 months improves rPFS by PSMA PET/CT compared with placebo plus ADT given for 12 months, and to further evaluate efficacy and to measure the treatment impact on patients’ quality of life, and to assess the safety of darolutamide plus ADT compared with placebo plus ADT.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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
(or refused) for 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 or central values accepted).

- 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.

Exclusion Criteria:

- 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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/01/2024. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jack Andrews, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available