What side effects are associated with this type of intervention?

Enzalutamide, a second-generation androgen receptor inhibitor, commonly causes fatigue, hot flashes, hypertension, and falls. It may also lead to more serious side effects such as seizures and posterior reversible encephalopathy syndrome (PRES). Docetaxel, a chemotherapy agent, frequently results in side effects like neutropenia, febrile neutropenia, fatigue, alopecia, and peripheral neuropathy. Both treatments can significantly impact the patient's quality of life and require careful monitoring by healthcare providers.

What prior FDA approvals exist?

Enzalutamide and docetaxel are FDA-approved treatments for metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide, an androgen receptor inhibitor, and docetaxel, a chemotherapy agent, have both shown efficacy in this setting. The ctDNA-guided trial is exploring the use of ctDNA as a predictive biomarker to direct treatment decisions between these two drugs, aiming to personalize therapy and enhance clinical outcomes.

What other types of research exist?

Promising novel alternatives to ctDNA-guided treatment selection for prostate cancer patients include: 1) Circulating cell-free DNA (cfDNA) as a biomarker for taxane resistance and overall prognosis. 2) Plasma tumor DNA (ptDNA) for early treatment response monitoring. 3) Bipolar androgen therapy (BAT) to resensitize tumors to androgen-directed therapies. 4) Lipidomic analysis combined with genetic aberrations to predict clinical outcomes. These approaches are under investigation and show potential for guiding treatment decisions in prostate cancer.

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Anti-mitotic Agent

ctDNA-Guided Therapy for Prostate Cancer (PROTRACT Trial)

Q: What is the mechanism of action of this treatment?

Enzalutamide and docetaxel are common treatments for prostate cancer. Enzalutamide works by inhibiting androgen receptors, blocking the effects of male hormones that can promote cancer growth. Docetaxel is a chemotherapy agent that prevents cancer cell division by stabilizing microtubules. These mechanisms are important for prostate cancer patients as they allow for personalized treatment strategies, potentially improving effectiveness and reducing side effects based on the cancer's molecular profile.

Phase 2

Recruiting

Research Sponsored by British Columbia Cancer Agency

Eligibility Criteria Checklist

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

Must have

Eligible for treatment with either enzalutamide or docetaxel as per standard of care guidelines

Evidence of biochemical or imaging progression in the setting of surgical or medical castration while on abiraterone. Progressive disease for study entry is defined by one of the following three criteria as per PCWG317:

Must not have

Uncontrolled hypertension Grade ≥3 (i.e. systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg)

Gastrointestinal disorder affecting absorption

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if using a blood marker to choose between two treatments is better than doctors choosing the treatment for advanced prostate cancer patients who did not respond to previous therapy.

Who is the study for?

This trial is for adult males over 18 with metastatic castration-resistant prostate cancer who have previously been treated with abiraterone. Participants must show disease progression, consent to tissue analysis, and have adequate organ function. They cannot join if they've had seizures, brain metastases, certain gastrointestinal disorders, prior enzalutamide or docetaxel chemotherapy (with exceptions), other active cancers (with exceptions), or uncontrolled hypertension.

What is being tested?

The study aims to optimize prostate cancer treatment by using circulating tumor DNA (ctDNA) levels to decide between two drugs: Enzalutamide for ctDNA fraction <2% and Docetaxel for ≥2%. This approach is compared against the clinician's choice of either drug without ctDNA guidance.

What are the potential side effects?

Enzalutamide may cause fatigue, back pain, constipation, joint pain and hot flushes. Docetaxel can lead to effects like low blood cell counts increasing infection risk, hair loss, nausea/vomiting and muscle aches.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am eligible for treatment with enzalutamide or docetaxel.

Select...

My prostate cancer has worsened despite treatment with abiraterone.

Select...

My PSA levels have increased twice from the baseline in a week, with a minimum of 1.0 ng/mL at screening.

Select...

My cancer has grown by 20% or I have new cancer spots since starting treatment.

Select...

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

Select...

My scans show cancer has spread to my bones or other parts.

Select...

I have been treated with abiraterone for prostate cancer.

Select...

I have recovered from previous cancer treatment side effects.

Select...

My kidneys work well enough (creatinine clearance ≥ 30 ml/min).

Select...

I have prostate cancer without certain rare features, and my PSA was over 20 when diagnosed.

Select...

I am a man aged 18 or older.

Exclusion Criteria

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

Select...

My blood pressure is not higher than 160/100 mmHg.

Select...

I have a digestive condition that affects how my body absorbs nutrients.

Select...

I have brain metastases or active epidural disease.

Select...

I have previously been treated with enzalutamide or similar drugs.

Select...

I cannot take prednisone due to my uncontrolled diabetes.

Select...

I have not had major surgery in the last 4 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression free survival (PFS)

Secondary study objectives

Clinical benefit rate (CBR)

Correlation of specific ctDNA-based genomic alterations to treatment response

Objective response

+3 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: A: Biomarker directed Therapy (BT)Experimental Treatment2 Interventions

ctDNA fraction \<2% receives enzalutamide, and ctDNA fraction ≥2% receives docetaxel until disease progression, then cross-over to the other therapy (e.g., enzalutamide to docetaxel, or docetaxel to enzalutamide).

Group II: B: Clinician's Choice (CC)Active Control2 Interventions

Enzalutamide or docetaxel until disease progression, then cross-over to the other therapy (e.g., enzalutamide to docetaxel, or docetaxel to enzalutamide).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Enzalutamide

2014

Completed Phase 4

~3820

Docetaxel

1995

Completed Phase 4

~6550

0 / 17Eligibility 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

Enzalutamide and docetaxel are common treatments for prostate cancer. Enzalutamide works by inhibiting androgen receptors, blocking the effects of male hormones that can promote cancer growth. Docetaxel is a chemotherapy agent that prevents cancer cell division by stabilizing microtubules. These mechanisms are important for prostate cancer patients as they allow for personalized treatment strategies, potentially improving effectiveness and reducing side effects based on the cancer's molecular profile.

Baseline Plasma Tumor DNA (ctDNA) Correlates with PSA Kinetics in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and Enzalutamide in Prostate Cancer.New therapies for castration-resistant prostate cancer: efficacy and safety.