What side effects are associated with this type of intervention?

Common treatments for prostate cancer, such as androgen synthesis enzyme inhibitors (e.g., abiraterone) and AKT inhibitors (e.g., afuresertib), have several known side effects. Androgen synthesis enzyme inhibitors can cause hypertension, hypokalemia, fatigue, and liver function abnormalities. AKT inhibitors may lead to hyperglycemia, diarrhea, rash, and fatigue. These side effects vary in severity and frequency among patients, and it is important to monitor and manage them under medical supervision.

What prior FDA approvals exist?

The FDA has approved several treatments for prostate cancer that target androgen synthesis and androgen receptors. Abiraterone acetate, an androgen synthesis inhibitor, has been approved for use in combination with prednisone for metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide, an androgen receptor inhibitor, is another FDA-approved drug for mCRPC. These treatments work by inhibiting the production or action of androgens, which are critical for the growth of prostate cancer cells. The combination of these drugs with other therapies, such as docetaxel, has also been explored to improve patient outcomes.

What other types of research exist?

Promising novel alternatives for prostate cancer treatment in 2024 include: <ol> <li>Enzalutamide: An androgen receptor inhibitor shown to improve survival in metastatic castration-resistant prostate cancer (mCRPC).</li> <li></li> </ol> Olaparib: A PARP inhibitor effective in patients with homologous recombination repair gene alterations, particularly those with BRCA mutations. 3. Ra-223: A radiopharmaceutical that targets bone metastases and has shown improved survival in combination with other therapies. 4. Darolutamide: An androgen receptor inhibitor recommended in combination with androgen deprivation therapy (ADT) and docetaxel for high-risk/high-volume metastatic castration-sensitive prostate cancer (mCSPC).

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Protein Kinase Inhibitor

LAE001 + Prednisone + Afuresertib for Prostate Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by Laekna Limited

Eligibility Criteria Checklist

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

Must have

Patients must have adequate renal function as evidenced by a serum creatinine of ≤1.5 × ULN for the reference laboratory or creatinine clearance ≥30 mL/min within the 28 days before enrollment.

Patients must have documented histological or cytological evidence of adenocarcinoma of the prostate (excluding neuroendocrine differentiation or small cell histology).

Must not have

Patients who require potassium-wasting diuretics.

Inadequately controlled hypertension or hypotension after up to 3 measurements with at least 5 minutes apart during 28 days before study enrollment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new combination of drugs for men with advanced prostate cancer that hasn't responded to other treatments. The drugs work by blocking proteins and hormones that help cancer grow. Researchers will find the best doses and see how well the treatment works.

Who is the study for?

This trial is for men over 18 with advanced prostate cancer that's resistant to castration and has spread, despite previous anti-androgen treatments. They must have a certain level of health, including stable blood sugar and kidney function, no major surgeries or infections recently, and not be on conflicting medications. Men must agree to use contraception if their partner can bear children.

What is being tested?

The study tests combining LAE001/prednisone with afuresertib in men whose prostate cancer has worsened after standard care. It aims to find the best dose mix for those intolerant or unresponsive to two prior anti-androgen therapies or chemotherapy.

What are the potential side effects?

Potential side effects may include issues related to hormone therapy like fatigue, hot flashes, mood swings; prednisone might cause weight gain or sleep problems; afuresertib could lead to digestive upset or rash. Specific side effects will depend on how patients react to the drug combination.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function is within the normal range based on recent tests.

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My prostate cancer is confirmed by lab tests and is not a neuroendocrine or small cell type.

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I have metastatic castration-resistant prostate cancer and have tried at least one treatment.

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My prostate cancer has spread, as confirmed by scans.

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My testosterone levels are very low.

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I have mCRPC and have had 1-3 prior treatments, including a second-gen antiandrogen, but no more than one chemo.

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I can take care of myself and am up and about more than half of my waking hours.

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I can take pills and don't have stomach or bowel problems affecting drug absorption.

Exclusion Criteria

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

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I need medication that reduces potassium in my body.

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My blood pressure hasn't been stable for the last month.

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I have a history of issues with my hypothalamus, pituitary gland, or adrenal glands.

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I am not on long-term steroids or other drugs that weaken my immune system.

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I am a sexually active male willing to use a condom during and for 16 weeks after the study.

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I have been treated with AKT, PI3K, or mTOR inhibitors before.

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I have a heart condition or have had heart problems in the past.

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I have an active HIV, hepatitis B, or hepatitis C infection.

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I am not on medications that strongly affect liver enzymes CYP1A or CYP3A.

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I do not have severe nerve pain or damage.

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I do not have another cancer that needs treatment right now.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 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

Combined Modality Therapy

Phase II: Radiological progression free survival (rPFS) based changes per Prostate Cancer Working Group 3 (PCWG3)

Phase II: Radiological progression free survival (rPFS) based on change in tumor per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Secondary study objectives

Phase I: Best PSA response

Phase I: Changes in Prostate Specific Antigen (PSA) levels

Phase I: Describe pharmacodynamics of study drugs

+21 more

Other study objectives

Phase I: Explore correlation between anti-tumor activity and patient's BRCA mutation status

Phase I: Explore correlation between anti-tumor activity and patient's PTEN status

Phase I: Relationship between PSA levels and testosterone levels

Awards & Highlights

No Placebo-Only Group

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

Trial Design

6Treatment groups

Experimental Treatment

Group I: Phase II Cohort 2Experimental Treatment1 Intervention

Docetaxel/prednisone + afuresertib

Group II: Phase II Cohort 1Experimental Treatment1 Intervention

LAE001 (capsules) + prednisone (tablet) +afuresertib at the Recommended Phase II Dose (RP2D)

Group III: Phase I Cohort 4Experimental Treatment1 Intervention

LAE001 (capsules) 100mg BID + prednisone (tablet) 5mg BID +afuresertib (tablet) 150mg QD will be administered in Cycles of 28 days.

Group IV: Phase I Cohort 3Experimental Treatment1 Intervention

LAE001 (capsules) 100mg BID + prednisone (tablet) 5mg BID +afuresertib (tablet) 125mg QD will be administered in Cycles of 28 days.

Group V: Phase I Cohort 2Experimental Treatment1 Intervention

LAE001 (capsules) 100mg BID + prednisone (tablet) 5mg BID +afuresertib (tablet) 100mg QD will be administered in Cycles of 28 days.

Group VI: Phase I Cohort 1Experimental Treatment1 Intervention

LAE001 (capsules) 75mg Twice Daily (BID) + prednisone (tablet) 5mg BID +afuresertib (tablet) 100mg Once Daily (QD) will be administered in Cycles of 28 days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Phase I and Phase II: LAE001/prednisone + afuresertib

2019

Completed Phase 2

~50

0 / 19Eligibility 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 androgen signaling pathways, crucial for prostate cancer cell growth. Androgen deprivation therapy (ADT) reduces androgen levels, while androgen receptor inhibitors block androgen receptor activity. Abiraterone inhibits androgen synthesis, reducing androgen production. Afuresertib, an AKT inhibitor, disrupts the AKT pathway, which is involved in cell survival and proliferation. LAE001, an androgen synthesis enzyme inhibitor, further reduces androgen levels. These mechanisms are vital as they directly interfere with the pathways that prostate cancer cells rely on for growth and survival, offering effective strategies for managing advanced and resistant forms of the disease.

Regulation of microtubule, apoptosis, and cell cycle-related genes by taxotere in prostate cancer cells analyzed by microarray.