What side effects are associated with this type of intervention?

Common treatments for prostate cancer, particularly those involving hormonal agents and targeted therapies, have a range of side effects. Hormonal agents like enzalutamide and abiraterone can cause fatigue, hypertension, hypokalemia, and increased risk of seizures. Docetaxel, a chemotherapy agent often used in combination with hormonal therapy, can lead to neutropenia, anemia, and gastrointestinal issues. PSMA-targeted therapies, such as 177Lu-PSMA-617, frequently cause anemia, fatigue, and xerostomia. These side effects are important considerations for patients undergoing treatment for advanced prostate cancer.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of prostate cancer, particularly those targeting the androgen receptor signaling pathway. Enzalutamide, apalutamide, and darolutamide are androgen receptor inhibitors that block androgen binding, nuclear translocation, and DNA association. These drugs are used in both metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Abiraterone, another FDA-approved drug, inhibits androgen biosynthesis and is often used in combination with prednisone. These treatments are similar to the ones being studied in the AZD5305 trial, which involves targeted therapy in combination with hormonal agents.

What other types of research exist?

Promising novel alternatives to AZD5305 for prostate cancer patients in 2024 include: 1) Enzalutamide combined with androgen deprivation therapy (ADT), which has shown improved survival in metastatic hormone-sensitive prostate cancer. 2) Radium-223 combined with osteoclast inhibitors, which has demonstrated reduced fracture risk and potential survival benefits in metastatic castration-resistant prostate cancer (CRPC). 3) Docetaxel combined with Ra-223, which has shown durable decreases in serum tumor markers in chemotherapy-naïve CRPC patients. These alternatives are supported by recent clinical trials and studies.

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Androgen Receptor Antagonist

AZD5305 + Hormonal Therapy for Prostate Cancer (PETRANHA Trial)

Phase 1 & 2

Recruiting

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Candidate for treatment with enzalutamide, abiraterone acetate, or darolutamide with documented current evidence of metastatic prostate cancer.

For Part B: Patients must have mCSPC (de novo or recurrent) with a baseline PSA value of ≥ 0.2 ng/mL

Must not have

For Part A and Part B mCSPC Patients: Any previous treatment with a PARP inhibitor, platinum, NHA, Immuno-oncology (IO), radiopharmaceutical therapy, or prior treatment with docetaxel in mCSPC setting.

Patients recruited to the PDc cohorts should not have received a prior use of new hormonal agents (NHA).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6, 12, 18, 24 and 30 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, AZD5305, combined with hormone treatments in patients with advanced prostate cancer. It aims to see if this combination is safe and effective. The study focuses on patients whose cancer either continues to grow despite hormone therapy or is still responsive to it.

Who is the study for?

Men over 18 with metastatic prostate cancer who are candidates for treatment with enzalutamide, abiraterone acetate, or darolutamide. They must be castrated (surgically or medically), have good organ and marrow function, an ECOG Performance Status of 0-1, a life expectancy of at least 16 weeks, and agree to use contraception if necessary. Not eligible if they've had certain prior treatments like PARP inhibitors in the mCSPC setting or strong CYP3A4 inducers.

What is being tested?

The trial is testing AZD5305 combined with new hormonal agents (NHAs) such as enzalutamide, abiraterone acetate, or darolutamide in men with metastatic prostate cancer. It aims to assess safety and how well the body handles the drug combination while also looking at early signs of effectiveness.

What are the potential side effects?

Possible side effects include typical reactions to hormone therapies like fatigue, digestive issues and potential changes in liver function tests. Since this is a study combining drugs there may be additional unknown risks.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am eligible for specific prostate cancer treatments and my cancer has spread.

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I have metastatic castration-sensitive prostate cancer with a PSA level of at least 0.2 ng/mL.

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I have advanced prostate cancer that is resistant or sensitive to hormone therapy.

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I have undergone treatment to lower my testosterone levels.

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I am 18 years old or older.

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My prostate cancer has spread and was confirmed by a biopsy.

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I am fully active or have some restrictions but can still care for myself, with no worsening in the last 2 weeks.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not had treatments like PARP inhibitors or chemotherapy for my prostate cancer.

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I have not used new hormonal agents for my condition.

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I haven't had certain treatments or vaccines recently and don't have severe health issues.

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I am not taking medication that affects heart rhythm.

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I have mCRPC and have been treated with PARP inhibitors, Lu-PSMA, or platinum chemotherapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6, 12, 18, 24 and 30 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6, 12, 18, 24 and 30 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6, 12, 18, 24 and 30 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of patients with Adverse Events and Serious Adverse Events

Part A: Number of patients with Dose Limiting Toxicities (DLTs)

Secondary study objectives

AUC of AZD5305

AUC of Apalutamide

AUC of Enzalutamide

+19 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm 4 (AZD5305 in combination with apalutamide)Experimental Treatment1 Intervention

Patients will receive an oral dose of AZD5305 and Apalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group II: Arm 3 (AZD5305 in combination with darolutamide)Experimental Treatment2 Interventions

Patients will receive an oral dose of AZD5305 once daily and Darolutamide twice daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group III: Arm 2 (AZD5305 in combination with abiraterone acetate)Experimental Treatment2 Interventions

Patients will receive an oral dose of AZD5305 and Abiraterone Acetate once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Group IV: Arm 1 (AZD5305 in combination with enzalutamide)Experimental Treatment2 Interventions

Patients will receive an oral dose of AZD5305 and Enzalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Darolutamide

2018

Completed Phase 2

~100

Apalutamide

2015

Completed Phase 2

~5750

AZD5305

2022

Completed Phase 1

~20

Abiraterone Acetate

2015

Completed Phase 4

~1880

Enzalutamide

2014

Completed Phase 4

~3820

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for prostate cancer include hormonal agents and targeted therapies. Hormonal agents, such as abiraterone and enzalutamide, either inhibit androgen production or block androgen receptors, which are essential for prostate cancer cell growth. Targeted therapies, like PARP inhibitors, exploit specific weaknesses in cancer cells, such as deficiencies in DNA repair mechanisms. Combining these treatments can improve outcomes by attacking the cancer on multiple fronts, making it harder for the cancer cells to survive and proliferate. This approach is particularly relevant for advanced or metastatic prostate cancer, where single-agent therapies may be less effective.