Darolutamide + Androgen Deprivation Therapy (ADT) Compared With ADT Alone, for Chinese Men With High Risk, Nonmetastatic Prostate Cancer

Sponsor
Bayer (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05171387
Collaborator
(none)
102
1
2
39.1
2.6

Study Details

Study Description

Brief Summary

Researchers are looking for a better way to treat men who have non-metastatic castration resistant prostate cancer (nmCRPC). This is a type of cancer in the prostate that has not yet spread to other parts of the body and keeps progressing even when the amount of testosterone (androgen) is reduced to very low levels. Men with nmCRPC usually have higher levels of prostate-specific antigen (PSA) than normal. It is a protein that is made by both normal cells and by cancerous cells in the body. Androgen deprivation therapy (ADT) is a treatment that commonly used to lower the amount of hormones called androgens in the body.

The study drug, darolutamide, is already available for doctors to prescribe to patients with prostate cancer that has not yet spread to other parts of the body. It works by blocking hormones, called androgens, from attaching to proteins in cancer cells in the prostate. These hormones are thought to play a role in prostate cancer.

There has been a study to research how patients with nmCRPC benefit with darolutamide plus Androgen deprivation therapy (ADT) as compared to placebo plus ADT therapy.

In this focused study of Chinese participants, researchers will be using a "marker" of cancer- PSA- to detect when that marker increases as a sign that the cancer appears to be progressing. The researchers want to learn how much longer it will take for participants who are treated with darolutamide added to ADT to have a rise in their PSA levels, compared with the time for PSA to rise in men who are treated with ADT alone. In this study, time to "progress" will be defined by a documented and confirmed rise in PSA by> 25% from the baseline value ( and > 2 ng/mL above the lowest value measured). In previous studies, PSA was observed to rise approximately 8 mo.-1 year prior to the development of "metastasis" (tumor spread to other organs). By using the tumor marker PSA , researchers can more quickly identify how study participants are responding to their study treatment.

The participants in this study will take either darolutamide or a placebo. A placebo looks like a treatment but does not have any medicine in it. All the participants will also take ADT. Doctors are able to prescribe ADT to patients with prostate cancer.

During the study, the participants will take darolutamide or the placebo until:
  • their cancer spreads

  • they start another type of cancer treatment

  • they have adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

  • they take another type of medication that is not able to be taken during this study

  • they decide to leave the trial

  • the participant dies

The participants will visit the study site every 12 weeks during treatment and after stopping treatment. The whole study will last about 35 months. During the study, the doctors will:

  • check the participants' overall health and heart health

  • take blood samples

  • take pictures of the participants' tumors and bones using CT, MRI, and bone scans

  • ask the participants questions about how they are feeling, what medications they are taking, and what adverse events they are having.

Condition or Disease Intervention/Treatment Phase
  • Drug: Darolutamide 600 mg twice daily
  • Drug: Placebo 600 mg twice daily
  • Drug: Androgen deprivation therapy (ADT)
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
102 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Treatment period: The start of the treatment period is defined by the first administration of the study treatment. The participants will take 2 tablets (300 mg each tablet) of blinded study treatment (darolutamide or placebo) orally bid at about 12 hour intervals during double-blind phase. Cross over and unblinding at PSA progression: Participants who reach confirmed PSA (Prostate-specific antigen) progression during treatment will be unblinded. If metastases are not present, participants will receive open-label darolutamide. Participants in the darolutamide arm can continue open-label darolutamide if in the opinion of the investigator the participant continues to derive benefit from treatment with darolutamide. Participants in the control arm can cross over to open-label darolutamide treatment and will be able to continue this treatment until treatment discontinuation criteria.Treatment period:The start of the treatment period is defined by the first administration of the study treatment. The participants will take 2 tablets (300 mg each tablet) of blinded study treatment (darolutamide or placebo) orally bid at about 12 hour intervals during double-blind phase.Cross over and unblinding at PSA progression:Participants who reach confirmed PSA (Prostate-specific antigen) progression during treatment will be unblinded. If metastases are not present, participants will receive open-label darolutamide. Participants in the darolutamide arm can continue open-label darolutamide if in the opinion of the investigator the participant continues to derive benefit from treatment with darolutamide. Participants in the control arm can cross over to open-label darolutamide treatment and will be able to continue this treatment until treatment discontinuation criteria.
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled Phase 2 Study of Darolutamide Versus Placebo in Addition to Standard Androgen Deprivation Therapy for Participants With High-risk Non-metastatic Castration Resistant Prostate Cancer (nmCRPC)
Actual Study Start Date :
Nov 30, 2021
Anticipated Primary Completion Date :
Oct 26, 2024
Anticipated Study Completion Date :
Mar 3, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Double-blind treatment: Darolutamide in addition to Androgen deprivation therapy (ADT)

Participants in the darolutamide arm can continue open-label darolutamide if in the opinion of the investigator the participant continues to derive benefit from treatment with darolutamide. Androgen deprivation therapy (ADT) is a treatment that commonly used to lower the amount of hormones called androgens in the body.

Drug: Darolutamide 600 mg twice daily
The participants will take 2 tablets (300 mg each tablet) of blinded study treatment (darolutamide or placebo) orally bid at about 12 hour intervals during double-blind phase.

Drug: Androgen deprivation therapy (ADT)
Androgen deprivation therapy (ADT) is a treatment that commonly used to lower the amount of hormones called androgens in the body.

Placebo Comparator: Double-blind treatment: Placebo in addition to Androgen deprivation therapy (ADT)

Participants in the control arm can cross over to open-label darolutamide treatment and will be able to continue this treatment until treatment discontinuation criteria. Androgen deprivation therapy (ADT) is a treatment that commonly used to lower the amount of hormones called androgens in the body.

Drug: Placebo 600 mg twice daily
The participants will take 2 tablets (300 mg each tablet) of blinded study treatment (darolutamide or placebo) orally bid at about 12 hour intervals during double-blind phase.

Drug: Androgen deprivation therapy (ADT)
Androgen deprivation therapy (ADT) is a treatment that commonly used to lower the amount of hormones called androgens in the body.

Outcome Measures

Primary Outcome Measures

  1. Time to PSA (TTPSA) progression [when PSA is noted to increase 25% above baseline (or to increase more than 2 ng/ml above lowest value documented) rise in PSA will be confirmed by a second blood test obtained 3 or more weeks later"]

    PSA = Prostate-specific antigen; TTPSA progression is defined as the time from the date of randomization to the date of first PSA progression. The analysis will be performed when approximately 46 events are observed.

Secondary Outcome Measures

  1. Number of participants with: Adverse events (AEs) and serious adverse events (SAEs) [Up to 30 days after the last dose of treatment]

  2. Number of participants with: Discontinuations and dose modifications of study intervention (treatment) due to AEs [Up to 30 days after the last dose of treatment]

  3. Number of participants with: Laboratory abnormalities reported as AEs [Up to 30 days after the last dose of treatment]

    The investigator must review the laboratory report, document this review, and record any changes that are clinically relevant based on his/her clinical judgement, occurring during the study in the AE section of the CRF.

  4. Number of participants with: Changes in Electrocardiograms (ECGs) reported as AEs [Up to 30 days after the last dose of treatment]

  5. Number of participants with: Changes in physical examination outcomes reported as AEs [Up to 30 days after the last dose of treatment]

  6. Number of participants with: Changes in Eastern Cooperative Oncology Group (ECOG) performance status [Up to 30 days after the last dose of treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Participant must be ≥18 years of age inclusive, at the time of signing the informed consent.

  • Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.

  • Castration-resistant prostate cancer (CRPC) defined as 3 rising PSA levels after the nadir taken at least 1 week apart during ADT. If the participant has a history of antiandrogen use, the most recent PSA value must be obtained at least 4 weeks after antiandrogen withdrawal.

  • Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dl]) on GnRH agonist or antagonist therapy or after bilateral orchiectomy. Participants who have not undergone bilateral orchiectomy must continue GnRH therapy during the study.

  • Prostate-specific antigen doubling time (PSADT) of ≤ 10 months and PSA ≥ 2 ng/ml at screening.

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

  • Blood counts at screening: hemoglobin ≥ 9.0 g/dl, absolute neutrophil count ≥ 1500/μl (1.5x109/l), platelet count ≥ 100,000/μl (100x109/l ) (participant must not have received any growth factor or blood transfusion within 7 days of the hematology laboratory obtained at screening).

  • Screening values of serum alanine aminotransferase (ALT) and aspartate transaminase (AST) ≥ 2.5 x upper limit of normal (ULN), total bilirubin ≥ 1.5 x ULN (except participants with a diagnosis of Gilbert's disease), creatinine ≥ 2.0 x ULN.

  • Male: Sexually active participants, unless surgically sterile, must agree to use condoms as an effective barrier method and refrain from sperm donation during the study treatment and for 1 week after the end of the study treatment. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:
  • History of metastatic disease at any time or presence of detectable metastases assessed by the investigator within 42 days prior to start of study treatment. Presence of pelvic lymph nodes < 1.5 cm in short axis below the aortic bifurcation is allowed.

  • Symptomatic local-regional disease that requires medical intervention including moderate/severe urinary obstruction or hydronephrosis due to prostate cancer.

  • Acute toxicities of prior treatments and procedures not resolved to ≤ CTCAE v5.0 grade 1 or baseline before randomization.

  • Severe or uncontrolled concurrent disease, infection or co-morbidity that, in the opinion of the investigator, would make the participant inappropriate for enrollment.

  • Known hypersensitivity to the study treatment or any of its ingredients.

  • Major surgery within 28 days before randomization.

  • Any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.

  • Uncontrolled hypertension as indicated by a systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management at screening.

  • Prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e. pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed ≥ 5 years ago and from which the participant has been disease-free.

  • Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.

  • Active viral hepatitis, known human immunodeficiency virus (HIV) infection with detectable viral load, or chronic liver disease with a need of treatment.

  • Any condition that in the opinion of the investigator would impair the participants' ability to comply with the study procedures.

  • Unable to swallow study medications and/or comply with study requirements.

  • Prior treatment with:

  • second generation AR inhibitors such as enzalutamide, apalutamide, darolutamide, other investigational AR inhibitors

  • CYP17 enzyme inhibitor such as abiraterone acetate, TAK-700 or

  • oral ketoconazole longer than for 28 days (continuous use).

  • Use of estrogens or 5-α reductase inhibitors (finasteride, dutasteride) within 28 days before randomization and AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) at least 28 days before screening.

  • Prior chemotherapy or immunotherapy for prostate cancer, except adjuvant/neoadjuvant treatment completed > 2 years before randomization.

  • Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomization.

  • Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 12 weeks before randomization.

  • Treatment with an osteoclast-targeted therapy (bisphosphonate or denosumab) to prevent skeletal-related events within 12 weeks before randomization. Participants receiving osteoclast-targeted therapy to prevent bone loss at a dose and schedule indicated for osteoporosis may continue treatment at the same dose and schedule.

  • Treatment with any investigational drug within 28 days before randomization.

  • Treatment with any investigational drug, or Traditional Chinese Medication (TCM) that is approved as a cancer treatment, within 28 days before randomization.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Many Locations Multiple Locations China

Sponsors and Collaborators

  • Bayer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT05171387
Other Study ID Numbers:
  • 20963
First Posted:
Dec 28, 2021
Last Update Posted:
Aug 4, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 4, 2022