AZD5305 + Darolutamide for Prostate Cancer

(ASCERTAIN Trial)

Recruiting in Palo Alto (17 mi)

+16 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: AstraZeneca

Must not be taking: QT drugs, CYP3A4 drugs

Disqualifiers: Severe diseases, Cardiac issues, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

A Study to Investigate the Biological Effects of Saruparib (AZD5305) Alone, Darolutamide Alone, and in Combination Given Prior to Radical Prostatectomy in Men with Newly Diagnosed Prostate Cancer (ASCERTAIN).

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications or supplements that are strong CYP3A4 inducers/inhibitors or P-glycoprotein inducers at least 21 days before starting the study treatment. If you're taking any of these, you may need to stop or switch them.

What data supports the effectiveness of the drug combination AZD5305 + Darolutamide for prostate cancer?

Darolutamide, one of the drugs in the combination, has shown effectiveness in delaying metastasis (spread of cancer) and improving survival in men with nonmetastatic, castration-resistant prostate cancer. It works by blocking androgen receptors, which are involved in prostate cancer growth.

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Is the combination of AZD5305 and Darolutamide safe for humans?

Darolutamide has been shown to have a favorable safety profile in patients with prostate cancer, with a lower chance of side effects compared to similar drugs. It is considered safe for use in humans, but specific safety data for the combination with AZD5305 is not available.

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How is the drug AZD5305 + Darolutamide different from other prostate cancer treatments?

This treatment combines AZD5305, a novel drug, with darolutamide, a second-generation androgen receptor inhibitor that is effective in delaying metastasis in nonmetastatic, castration-resistant prostate cancer. Darolutamide is unique because it is structurally different from other androgen inhibitors and is taken orally, which may offer convenience compared to other treatment options.

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Eligibility Criteria

Men over 18 with newly diagnosed, localized prostate cancer suitable for surgery can join. They must have a biopsy sample available and be able to consent. Participants should not plan to father children and must use condoms during the study. Those with heart issues, severe diseases, or taking certain drugs affecting heart rhythm or immune system are excluded.

Inclusion Criteria

I am a man older than 18.

Participants must use a condom (with spermicide) from screening to 6 months after screening and refrain from fathering a child or donating sperm

My organs and bone marrow are working well.

Exclusion Criteria

I have heart or blood vessel problems, including recent heart attacks or strokes.

I do not have severe illnesses or infections like HepB, hepatitis C, or HIV.

I have a bleeding disorder or a history of blood cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Saruparib (AZD5305) alone, Darolutamide alone, or in combination for 21 days (+ up to 7 days) prior to radical prostatectomy

3-4 weeks

Daily administration

Surgery

Participants undergo radical prostatectomy following the treatment phase

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment and surgery

4 weeks

Participant Groups

The trial is testing AZD5305 alone, Darolutamide alone, and their combination in men before they undergo prostate removal surgery. The goal is to understand how these treatments affect prostate cancer at a biological level.

Group I: Saruparib (AZD5305) only Experimental Treatment 1 Intervention

Participant will receive Saruparib (AZD5305) once daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days)

Group II: Saruparib (AZD5305) + Darolutamide Experimental Treatment 2 Interventions

Participant will receive Saruparib (AZD5305) once daily + darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days).

Group III: No Treatment Experimental Treatment 1 Intervention

No study treatment is to be taken by the participants in this arm. Radical prostatectomy should be performed as per local practice

Group IV: Darolutamide Only Experimental Treatment 1 Intervention

Participant will receive darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days).

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Research Site Québec, Canada

Research Site Detroit, MI

Research Site Providence, RI

Research Site Vancouver, Canada

More Trial Locations

Who Is Running the Clinical Trial?

AstraZeneca Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. [2019] Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths among men. Androgen receptor (AR) signaling plays a key role in PC tumor growth and progression, with androgens stimulating PC proliferation and survival. Castration-resistant PC (CRPC) is characterized by increasing levels of prostate-specific antigen or radiographic progression despite androgen-deprivation therapy (ADT). In most patients, castration resistance results from aberrations in AR or the AR signaling pathway. Up to one-third of patients with localized high-risk PC will have disease progression on local therapy and develop CRPC. This review summarizes the key clinical data, including ongoing trials, for hormonal therapies in CRPC and provides an overview of the clinical development of darolutamide, a novel, nonsteroidal AR antagonist currently in phase III development for the treatment of nonmetastatic CRPC and metastatic hormone-sensitive PC. In phase I/II trials, darolutamide has demonstrated a favorable safety profile, antitumor activity, and significant decreases in prostate-specific antigen in patients with metastatic CRPC. In the phase III ARAMIS (NCT02200614; A Multinational, Randomized, Double-Blind, Placebo-Controlled, Phase III Efficacy and Safety Study of Darolutamide [ODM-201] in Men With High-Risk Non-metastatic Castration-Resistant Prostate Cancer) study, metastasis-free survival is being evaluated in men with nonmetastatic CRPC who will receive ADT in combination with darolutamide or placebo. The ARASENS (NCT02799602; A Randomized, Double-Blind, Placebo Controlled Phase III Study of Darolutamide [ODM-201] Versus Placebo in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone Sensitive Prostate Cancer) study is a placebo-controlled trial assessing whether the addition of darolutamide to ADT and docetaxel significantly prolongs overall survival in men with metastatic hormone-sensitive PC.

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. [2023] Darolutamide and enzalutamide are second-generation androgen receptor inhibitors with activity in men with castrate-resistant prostate cancer (CRPC) and different toxicity profiles.

3. Netherlands pubmed.ncbi.nlm.nih.gov

[Androgen receptor inhibitors in prostate cancer: new drugs, but for which patient?] [2020] The results of a recent randomised phase 3 clinical trial show that the androgen receptor antagonist darolutamide improves metastasis-free survival in men with non-metastatic, castration-resistant prostate cancer, compared with placebo. The trial included 1509 men with a prostate-specific antigen doubling time of 10 months or less. Non-metastatic disease was defined as the absence of metastases, using conventional imaging rather than the substantially more sensitive PSMA scans. The effect of darolutamide is similar to that of other androgen inhibitors, such as apalutamide and enzalutamide. The value of the current trial to Dutch clinical practice is limited, as the number of patients with non-metastatic, castration-resistant prostate cancer is low due to the increased use of PSMA scans and the reluctance of urologists to start androgen-deprivation therapy in the absence of metastatic disease.

4. United States pubmed.ncbi.nlm.nih.gov

Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. [2023] Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown.

5. United States pubmed.ncbi.nlm.nih.gov

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. [2022] Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics of the Androgen Receptor Inhibitor Darolutamide in Healthy Subjects and Patients with Hepatic or Renal Impairment. [2022] Darolutamide is a second-generation androgen receptor inhibitor approved for the treatment of nonmetastatic castration-resistant prostate cancer at a dosage of 600 mg orally twice daily.

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial. [2023] In patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable safety/tolerability profile. This post hoc analysis of ARAMIS evaluated efficacy and safety in patients by number of comorbidities and concomitant medications.

8. England pubmed.ncbi.nlm.nih.gov

An up-to-date evaluation of darolutamide for the treatment of prostate cancer. [2021] Introduction: Currently, in prostate cancer, an increasing number of novel drugs are being used to delay its advancement to metastatic castration-resistant prostate cancer (mCRPC). Apalutamide, enzalutamide, and most recently, darolutamide (novel androgen receptor antagonists) have been approved for nonmetastatic castration-resistant prostate cancer (nmCRPC).Areas covered: The authors have evaluated darolutamide, covering all aspects of the clinical development, competence, and safety profile of the drug.Expert opinion: The unique structure of darolutamide is characterized by a high affinity for androgen receptors and detainment of antagonist activity in mutant isoforms of androgen receptors. In clinical practice, this is the main reason that makes darolutamide exceptional in terms of safety and efficacy compared to other drugs in this category. Darolutamide is considered to have the lowest probability for adverse events (AEs) compared to apalutamide and enzalutamide. Future studies, along with real-world clinical data are warranted to improve personalized treatment strategies as well as sequencing treatment between approved novel drugs.

9. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and safety of darolutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a sub-group analysis of the phase III ARAMIS trial. [2022] Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here.

10. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 study of darolutamide (ODM-201): a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. [2023] This trial assessed the safety, pharmacokinetics, and efficacy of darolutamide (ODM-201), a new-generation nonsteroidal androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC).