ctDNA-Guided Therapy for Prostate Cancer

(PROTRACT Trial)

Not currently recruiting at 6 trial locations

Overseen By Corinne Maurice-Dror, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: British Columbia Cancer Agency

Must be taking: LHRH agonist/antagonist

Must not be taking: Anti-androgens, Chemotherapy

Disqualifiers: Severe illness, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Until disease progression

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for selecting treatments for men with metastatic prostate cancer that has resisted other therapies. By using a blood test to measure a specific DNA marker, researchers can determine whether participants should receive enzalutamide (a hormone therapy) or docetaxel (a chemotherapy drug), both standard treatments. Men battling prostate cancer, particularly if it has spread to bones or lymph nodes and stopped responding to previous treatments, might be suitable for this study. The goal is to assess if this DNA-guided approach is more effective than allowing doctors to choose the treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in prostate cancer care.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must maintain LHRH agonist/antagonist therapy if not surgically castrated. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both docetaxel and enzalutamide are commonly used to treat prostate cancer, with important safety information available for each.

For docetaxel, studies indicate it can extend the lives of men with metastatic prostate cancer. However, in one study, about 34% of patients receiving docetaxel were hospitalized, and 17 patients experienced febrile neutropenia. This serious condition involves a fever and low white blood cell levels, increasing infection risk.

Enzalutamide has also improved survival rates. In one study, it reduced the risk of death by 33% compared to other treatments. Enzalutamide is generally well-tolerated, but like all medications, it can cause side effects. Some patients may feel tired or experience high blood pressure.

Both treatments have been used in previous studies and are FDA-approved for prostate cancer, indicating a well-known safety profile. However, anyone considering joining a clinical trial should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it uses a ctDNA-guided approach to tailor prostate cancer treatment more precisely. Unlike traditional methods that might use a one-size-fits-all approach, this trial leverages circulating tumor DNA (ctDNA) levels to decide between administering enzalutamide or docetaxel. This personalized strategy could maximize the effectiveness of treatment by switching therapies when the disease progresses, potentially leading to better outcomes and improved patient management. The ability to dynamically adjust treatment based on ctDNA levels is a cutting-edge approach that could revolutionize how prostate cancer is managed.

What evidence suggests that this trial's treatments could be effective for metastatic castration-resistant prostate cancer?

Research has shown that both docetaxel and enzalutamide effectively treat prostate cancer. In this trial, participants in the Biomarker Directed Therapy arm will receive enzalutamide if their ctDNA fraction is less than 2%, and docetaxel if it is 2% or higher, with the option to switch to the other therapy upon disease progression. In the Clinician's Choice arm, participants will receive either enzalutamide or docetaxel, with a similar option to switch. Docetaxel can significantly lower the risk of death, especially when combined with standard care, and is generally well-tolerated. Enzalutamide has been proven to extend patients' lives and slow disease progression, reducing the risk of death by 33% compared to other treatments. Both treatments have strong evidence supporting their effectiveness in managing prostate cancer, offering different approaches to treating the disease. ^{2 3 6 7 8}

Who Is on the Research Team?

Kim N Chi, MD

Principal Investigator

British Columbia Cancer Agency

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My bone scans show at least 2 new lesions, confirmed 8 weeks apart.

I am eligible for treatment with enzalutamide or docetaxel.

My prostate cancer has worsened despite treatment with abiraterone.

Exclusion Criteria

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

I have had chemotherapy with docetaxel or cabazitaxel, except if it was for early-stage disease and I didn't worsen for 12 months after.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either biomarker-directed therapy or clinician's choice of enzalutamide or docetaxel until disease progression, with a cross-over to the other therapy upon progression

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Extension

Participants may continue to be monitored for overall survival and other outcomes

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Enzalutamide

Trial Overview 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.

How Is the Trial Designed?

Group I: A: Biomarker directed Therapy (BT) Experimental Treatment 2 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 Control 2 Interventions

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

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Published Research Related to This Trial

Docetaxel-based therapy has been shown to provide a survival benefit for men with metastatic prostate cancer, marking a significant advancement beyond palliative care options.

Ongoing trials are exploring various combination therapies with docetaxel, but the best timing for initiating treatment remains unclear due to a lack of prospective clinical trial data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Petrylak, DP.[2022]

In a study of 25 patients with advanced androgen-independent prostate cancer, docetaxel at a higher dose of 100 mg/m showed a 52% overall PSA response rate, with 60% of patients experiencing pain relief.

Despite its efficacy, the treatment had a significant toxicity profile, including severe neutropenia in 76% of patients, indicating that while docetaxel is effective, its use should be cautious and not routine due to the high risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of higher dose docetaxel in androgen-independent prostate cancer. Laber, DA., Glisson, SD., Hargis, JB., et al.[2018]

Enzalutamide (XTANDI) is an FDA-approved treatment for castration-resistant prostate cancer (CRPC) that effectively targets androgen receptor signaling, which is crucial for cancer progression.

In a Phase III clinical trial involving men with CRPC after chemotherapy, enzalutamide was well tolerated and significantly improved overall survival by 4.8 months, as indicated by reduced serum prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. Dhingra, R., Sharma, T., Singh, S., et al.[2021]

The combination of docetaxel and enzalutamide is feasible for treating metastatic castration-resistant prostate cancer (mCRPC), with 22 patients showing significant reductions in prostate-specific antigen levels, indicating potential efficacy.

However, the treatment was associated with higher-than-expected rates of neutropenia and fatigue, suggesting that while the combination is tolerable, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer. Morris, MJ., Rathkopf, DE., Novotny, W., et al.[2021]

Docetaxel-based treatments have shown effectiveness in managing advanced, androgen-independent prostate cancer, achieving significant palliative responses and reducing PSA levels by over 50% in patients.

Ongoing phase III trials are expected to provide crucial data on the impact of docetaxel on overall survival, while preliminary studies suggest that combining docetaxel with other novel agents is safe and may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in the integrated management of prostate cancer. Current applications and future promise. Logothetis, CJ.[2018]

The presence of circulating tumor cells (CTCs) before docetaxel treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) is linked to poorer outcomes, with a significant decrease in overall survival (OS) observed in patients with higher CTC counts.

Combining CTC measurements with clinical biomarkers like PSA and ALP can enhance the prediction of treatment response and patient outcomes, indicating that CTC analysis may serve as a valuable tool for personalizing therapy in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of using circulating tumour cells and their gene expression to predict docetaxel response in metastatic prostate cancer. Davies, CR., Guo, T., Burke, E., et al.[2023]

In a phase III trial involving metastatic castration-resistant prostate cancer patients, baseline circulating tumor cell (CTC) counts were found to be a strong predictor of overall survival, with patients having fewer than five CTCs per 7.5 mL showing a median survival of 26 months compared to just 13 months for those with five or more CTCs.

A rise in CTC counts from baseline to day 21 was associated with significantly shorter overall survival, indicating that monitoring CTC levels could serve as an early indicator to adjust treatment strategies for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. Goldkorn, A., Ely, B., Quinn, DI., et al.[2022]

In a study of 83 Chinese patients with metastatic hormone-refractory prostate cancer, docetaxel plus prednisone showed a higher efficacy compared to mitoxantrone plus prednisone, with 43.2% of patients achieving a complete or partial response versus 33.3% for mitoxantrone.

Docetaxel plus prednisone also provided better PSA control, with an average time to PSA progression of 37.8 weeks compared to 25.3 weeks for mitoxantrone, although it was associated with slightly higher toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel plus prednisone versus mitoxantrone plus prednisone for metastatic hormone-refractory prostate cancer in Chinese patients: experience of a single center. Zhang, HL., Ye, DW., Yao, XD., et al.[2018]

This study developed a method to analyze AR gene rearrangements in circulating tumor cells (CTCs) and plasma cell-free DNA (cfDNA) from ten patients with castration-resistant prostate cancer (CRPC), demonstrating the feasibility of detecting genetic alterations in both sources.

The analysis revealed a high frequency of discordant genetic alterations between CTC DNA and cfDNA, indicating that using both types of samples may provide a more comprehensive understanding of the genetic diversity in CRPC, which could impact treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AR gene rearrangement analysis in liquid biopsies reveals heterogeneity in lethal prostate cancer. Daniel, M., Knutson, TP., Sperger, JM., et al.[2022]

Docetaxel (Taxotere) has shown a significant survival advantage over the previously used treatment mitoxantrone in patients with hormone-refractory prostate cancer, based on results from two Phase III trials.

The treatment with docetaxel was well tolerated by patients, making it a promising standard for future prostate cancer therapies and trials involving new molecular treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel for the treatment of prostate cancer. Gilbert, DC., Parker, C.[2018]

In a study of 53 patients newly diagnosed with metastatic castrate-sensitive prostate cancer (mCSPC), circulating tumor DNA (ctDNA) was found to provide additional clinically relevant information compared to traditional prostate biopsies, identifying potential driver mutations in 94% of patients.

However, androgen deprivation therapy (ADT) significantly reduced ctDNA levels, highlighting the importance of using both tissue and liquid biopsies for comprehensive molecular profiling at diagnosis, as neither method alone captured all relevant alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer. Vandekerkhove, G., Struss, WJ., Annala, M., et al.[2019]

Docetaxel-based therapy has been shown to provide a significant survival benefit (20% to 24%) for men with metastatic hormone-refractory prostate cancer compared to previous treatments, leading to its FDA approval.

Ongoing clinical trials are exploring combinations of docetaxel with other therapies, including those targeting bone and tumor vasculature, as well as immune therapies, to improve treatment outcomes and define optimal treatment sequencing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New paradigms for advanced prostate cancer. Petrylak, DP.[2022]

The FDA has approved the combination of mitoxantrone and prednisone for hormone-refractory prostate cancer due to its superior palliative effects compared to steroids alone, based on two randomized trials.

A new phase III trial by the Southwest Oncology Group will compare the effectiveness of estramustine plus docetaxel against the standard treatment of mitoxantrone and prednisone, focusing on time to progression and survival, while also evaluating side effects and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. Hussain, M., Petrylak, D., Fisher, E., et al.[2018]

Docetaxel is the first treatment to significantly improve survival rates in patients with hormone-refractory prostate cancer, and it is now being tested in earlier stages of the disease to prevent recurrence in high-risk patients.

Pilot studies indicate that using docetaxel as a neo-adjuvant treatment can be done safely without increasing surgical risks, and ongoing randomized trials will further assess its effectiveness when combined with hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-risk localized prostate cancer: integrating chemotherapy. Oh, WK.[2018]

Citations

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Real‑world data on the outcomes of upfront docetaxel in ... The present study demonstrated that upfront docetaxel chemotherapy may be an effective and tolerable treatment for hormone-sensitive metastatic ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2589004225005103

Article Real-world effectiveness of novel hormonal agents ... Our results indicate that patients treated with NHAs experience comparable OS and PSA-PFS to those treated with docetaxel, yet they require less ...

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Mortality Risk for Docetaxel-Treated, High-Grade Prostate ... Adding docetaxel to SOC treatment in patients who were in otherwise good health was associated with a significant reduction in death due to prostate cancer.

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Real‑world data on the outcomes of upfront docetaxel ... The present study demonstrated that upfront docetaxel chemotherapy may be an effective and tolerable treatment for hormone‐sensitive metastatic prostate cancer.

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14575-1

Assessing the clinical outcomes of immunotherapy and ... Assessing the clinical outcomes of immunotherapy and docetaxel combinations in metastatic castration-resistant prostate cancer: a meta-analysis.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28940952/

Real-world uptake, safety profile and outcomes of ... Results: Of the 270 eligible patients, 103 received docetaxel (38.1%). 35 patients (34%) were hospitalised and there were 17 episodes of febrile neutropenia ( ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/215813s000lbl.pdf

DOCETAXEL injection, for intravenous use - accessdata.fda.gov For metastatic castration-resistant prostate cancer, the recommended dose of Docetaxel Injection is. 75 mg/m2 every 3 weeks as a 1-hour intravenous infusion.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00242918

Safety and Effectiveness Study of Docetaxel and ZD1839 ... The critical issue is in addressing micrometastatic disease that has already developed prior to diagnosis. This study utilizes daily doses of ZD1839 and weekly ...