What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as androgen receptor inhibitors (e.g., apalutamide), CYP17 inhibitors (e.g., abiraterone acetate), and corticosteroids (e.g., prednisone or prednisolone), have several known side effects. Androgen receptor inhibitors can cause fatigue, hypertension, rash, and a risk of seizures. CYP17 inhibitors are associated with hypertension, hypokalemia, fluid retention, and liver function abnormalities. Corticosteroids can lead to increased blood sugar levels, weight gain, and a higher risk of infections. Combining these treatments may amplify these side effects, necessitating careful monitoring and management by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that involve androgen receptor inhibitors and CYP17 inhibitors used with corticosteroids. Enzalutamide, an androgen receptor inhibitor, has been approved for use in both metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic CRPC. Abiraterone Acetate, a CYP17 inhibitor, is approved for use in combination with prednisone for mCRPC. Apalutamide, another androgen receptor inhibitor, has been approved for metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic CRPC. These approvals highlight the effectiveness of targeting androgen receptor pathways and steroid synthesis in managing advanced prostate cancer.

What other types of research exist?

Promising alternatives to Apalutamide in combination with Abiraterone Acetate plus Prednisone/Prednisolone for prostate cancer treatment include Darolutamide combined with Docetaxel and ADT, and Enzalutamide, which has shown increased survival benefits in metastatic castration-resistant prostate cancer patients.

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Androgen Synthesis Inhibitor

Apalutamide + Abiraterone Acetate + Prednisone for Prostate Cancer

Phase 3

Waitlist Available

Research Sponsored by Aragon Pharmaceuticals, Inc.

Eligibility Criteria Checklist

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

Must have

Prostate cancer progression documented by prostate-specific antigen (PSA) according to the Prostate Cancer Clinical Trials Working Group (PCWG2) or radiographic progression of soft tissue according to modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) modified based on PCWG2, or radiographic progression of bone according to PCWG2

Participants who received a first generation anti-androgen (eg, bicalutamide, flutamide, nilutamide) must have at least a 6-week washout prior to randomization and must show continuing disease (PSA) progression (an increase in PSA) after the washout period

Must not have

Therapies that must be discontinued or substituted at least 4 weeks prior to randomization include the following: a) Medications known to lower the seizure threshold, b) Herbal and non-herbal products that may decrease PSA levels (example [eg], saw palmetto, pomegranate) or c) Any investigational agent

Small cell or neuroendocrine carcinoma of the prostate

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years and 10 months

Awards & highlights

Pivotal Trial

Summary

This trial tests apalutamide added to a standard treatment for advanced prostate cancer. It targets patients whose cancer has spread and who haven't had chemotherapy. The treatment works by blocking and lowering male hormones that help cancer grow. Apalutamide has shown efficacy in treating different stages of prostate cancer.

Who is the study for?

Men with advanced prostate cancer that hasn't spread to the brain and haven't had chemotherapy. They must have a specific type of tumor (adenocarcinoma), evidence of metastasis, and show cancer progression despite hormone therapy. Prior use of certain anti-androgens is allowed if followed by disease progression.

What is being tested?

The trial tests if adding Apalutamide to standard treatment with Abiraterone Acetate and Prednisone improves outcomes in men with metastatic castration-resistant prostate cancer who haven’t received chemotherapy compared to the standard treatment alone.

What are the potential side effects?

Possible side effects include fatigue, digestive issues, skin rash, weight loss, joint pain, high blood pressure, and potentially increased risk for falls or fractures due to bone weakening.

Eligibility Criteria

Inclusion Criteria

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

Select...

My prostate cancer has worsened, shown by rising PSA levels or changes in scans.

Select...

I stopped taking my first-generation anti-androgen medication over 6 weeks ago and my prostate cancer is still getting worse.

Select...

I have been diagnosed with prostate adenocarcinoma.

Select...

My cancer has spread, confirmed by scans, with any lymph node spread larger than 2cm.

Select...

My prostate cancer is growing despite hormone therapy, with rising PSA levels.

Exclusion Criteria

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

Select...

I stopped taking medications that can cause seizures and supplements that lower PSA levels 4 weeks ago.

Select...

My prostate cancer is of a specific type: small cell or neuroendocrine.

Select...

I need strong painkillers for my condition.

Select...

I have been treated with ketoconazole for my prostate cancer for more than a week.

Select...

I have brain metastases.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years and 10 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years and 10 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years and 10 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

Radiographic Progression-free Survival (rPFS)

Secondary study objectives

Overall Survival (OS)

Time to Chronic Opioid Use

Time to Initiation of Cytotoxic Chemotherapy

+1 more

Side effects data

From 2021 Phase 2 trial • 86 Patients • NCT03279250

74%

Hot flashes

71%

Fatigue

44%

Anemia

38%

Hyperglycemia

26%

AST increase

26%

Hypertension

26%

Lipase increase

24%

ALT increase

24%

Dry skin

21%

Rash

18%

ACTH increase

18%

Cholesterol high

15%

Dizziness

15%

Amylase increase

12%

Memory impairment

12%

White blood cell decrease

12%

Constipation

12%

Lymphocyte count decrease

Myalgia

Paresthesia

Weight loss

Arthralgia

Hypothyrodism

LDH increase

Erectile dysfunction

Headache

Personality change

Dysgeusia

Dyspnea

HbA1c increased

Hypertriglyceridemia

Insomnia

Irritability

Anorexia

Atrial fibrillation

Anxiety

Bruising

Hypercalcemia

Dehydration

TSH increased

100%

80%

60%

40%

20%

Study treatment Arm

Arm B (LHRHa, Apalutamide, Abiraterone Acetate)

Arm A (LHRHa, Apalutamide)

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Group 1: AAP and apalutamideExperimental Treatment3 Interventions

Participants will receive apalutamide 240 milligram (mg) (4\*60 mg tablets) and abiraterone acetate (AA) 1000 mg (4\*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily, until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the Open-Label Extension (OLE) or Long-Term Extension (LTE) phase (AAP + open label apalutamide or AAP alone).

Group II: Group 2: AAP and PlaceboPlacebo Group3 Interventions

Participants will receive matching Placebo of apalutamide and abiraterone acetate (AA) 1000 mg (4\*250 mg tablets) once daily on an empty stomach and 5 mg prednisone (P), AAP, twice daily until disease progression, unacceptable toxicity or end of treatment, whichever occurs first. After unblinding participants will be offered further treatment as defined in the OLE or LTE phase (AAP + open label apalutamide or AAP alone).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Prednisone

2014

Completed Phase 4

~2500

Apalutamide

2015

Completed Phase 2

~5710

Abiraterone acetate

2014

Completed Phase 3

~3440

0 / 10Eligibility 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

Prostate cancer treatments often target the androgen receptor pathway, crucial for prostate cancer cell growth. Androgen receptor inhibitors like apalutamide block the androgen receptor, preventing androgens from stimulating cancer cells. CYP17 inhibitors such as abiraterone acetate inhibit the enzyme CYP17, reducing androgen production both in the testes and adrenal glands, thereby lowering overall androgen levels. Corticosteroids like prednisone or prednisolone are used to mitigate side effects of other treatments and reduce inflammation. These mechanisms are vital as they collectively reduce androgen levels and block androgen receptor activity, slowing cancer progression and improving patient outcomes.