ADT with or without Docetaxel for Prostate Cancer

Overseen By Study Coordinator

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Northwestern University

Must be taking: ADT

Must not be taking: Second generation ARPIs

Disqualifiers: Stroke, Myocardial infarction, Uncontrolled hypertension, 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: 12 weeks

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II, randomized, open label study comparing first line therapy with AThis is a phase II, randomized, open label study comparing first line therapy with ADT + abiraterone (doublet arm) or ADT + abiraterone + docetaxel (triplet arm) in low volume, metastatic hormone sensitive prostate cancer (mHSPC). This is a phase II, randomized, open label study comparing first line therapy with Androgen Deprivation Therapy (ADT) + abiraterone (doublet arm) or ADT + abiraterone + docetaxel (triplet arm) in low volume, metastatic hormone sensitive prostate cancer (mHSPC). The hypothesis being asked in this trial is whether first line treatment with ADT plus an androgen receptor pathway inhibitor (abiraterone) as a doublet regimen compared to ADT plus an androgen receptor pathway inhibitor (abiraterone) and docetaxel, as a triplet regimen results in superior outcomes for patients with low volume mHSPC. We plan to enroll patients with mHPSC that meet the CHAARTED criteria for low disease volume. Patients will be randomized 1:1 to either treatment arm: * doublet arm: abiraterone +ADT or * triplet arm: abiraterone + ADT + docetaxel. All subjects must receive ADT of the Investigator's choice (LHRH agonist/antagonists or orchiectomy) as standard therapy, started = 12 weeks before randomization.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot use certain medications like strong CYP3A4 inhibitors or participate in another clinical study with investigational drugs. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of ADT with or without Docetaxel for prostate cancer?

Research shows that adding docetaxel or abiraterone to androgen deprivation therapy (ADT) can improve survival in men with metastatic prostate cancer. Studies like STAMPEDE and CHAARTED found that these combinations help patients live longer compared to using ADT alone. ^{1 2 3 4 5}

Is the combination of ADT with Docetaxel or Abiraterone generally safe for humans?

The combination of ADT with Docetaxel or Abiraterone has been studied in men with metastatic prostate cancer, showing survival benefits. However, safety considerations such as fitness for chemotherapy, patient health conditions, and potential side effects should be taken into account when choosing a treatment plan. ^{1 2 5 6 7}

How does the drug combination of ADT with Docetaxel and Abiraterone differ from other prostate cancer treatments?

This treatment combines androgen deprivation therapy (ADT) with either Docetaxel or Abiraterone, which has shown a survival benefit for patients with metastatic prostate cancer compared to ADT alone. The combination is particularly beneficial for high-risk or high-volume metastatic cases, offering a more aggressive approach than standard ADT. ^{1 3 5 6 8}

Research Team

Sarah Fenton

Principal Investigator

Northwestern University

Eligibility Criteria

Men with low volume metastatic hormone-sensitive prostate cancer who have started androgen deprivation therapy within the last 12 weeks. They must be in good physical condition (ECOG ≤1), have proper organ and bone marrow function, understand the study, and consent to participate. No prior chemotherapy for prostate cancer is allowed, except as specified.

Inclusion Criteria

My prostate cancer has spread, confirmed by scans.

I started hormone therapy for my cancer less than 12 weeks ago.

My cancer has spread to a few bones or lymph nodes but not to my organs.

Exclusion Criteria

You are not currently participating in any other experimental treatments.

Known hypersensitivity to any of the study drugs, study drug classes or excipients in the formation of any of the study drugs.

My hepatitis B is under control with treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ADT + abiraterone (doublet arm) or ADT + abiraterone + docetaxel (triplet arm). Abiraterone is administered in 12-week cycles, and docetaxel is given on day 1 of each 21-day cycle.

12 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of progression-free survival and overall survival.

Up to 1 year

Quality of Life Assessment

Quality of Life is assessed using the FACT-P QoL assessment tool.

Throughout treatment and up to 30 days after the last dose

Treatment Details

Interventions

• Abiraterone
• ADT
• Docetaxel

Trial Overview This trial compares two treatments: ADT + abiraterone versus ADT + abiraterone + docetaxel for first-line therapy in men with low volume mHSPC. It's a phase II study where patients are randomly assigned to one of these treatment arms to see which provides better outcomes.

Participant Groups

Group I: Triplet Arm Experimental Treatment 3 Interventions

Abiraterone+Docetaxel+ADT Abiraterone Abiraterone acetate will be four (250 mg) tablets (total dose/day 1000 mg). Abiraterone administration is per a 12-week cycle. Abiraterone must be taken with prednisone. Prednisone will be provided as 5 mg tablets. Docetaxel Docetaxel on day 1 of each 21-day cycle, 75 mg/m2 via IV. Dexamethasone will be self-administered by the patient at 16 mg per day for 3 days starting 1 day prior to docetaxel infusion. ADT Patients may be started on an LHRH agonist or antagonist , the selection of the agent is left to the treating investigator for ADT.

Group II: Doublet Arm Active Control 2 Interventions

Abiraterone+ADT Abiraterone Abiraterone acetate will be four (250 mg) tablets (total dose/day 1000 mg). Abiraterone administration is per a 12-week cycle. Treatment of abiraterone should start ≤14 days after patient randomization. Abiraterone must be taken with prednisone. Prednisone will be provided as 5 mg tablets. Docetaxel Docetaxel on day 1 of each 21-day cycle, 75 mg/m2 via IV. Prior to docetaxel, dexamethasone administration is recommended as discussed, but can be adjusted or altered per the treating investigator's discretion. Dexamethasone will be self-administered by the patient at 16 mg per day for 3 days starting 1 day prior to docetaxel infusion.

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

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Adding docetaxel or abiraterone to androgen-deprivation therapy (ADT) significantly improves overall survival in men with newly diagnosed metastatic prostate cancer, based on evidence from multiple studies involving thousands of participants.

The strongest survival benefits from docetaxel are observed in patients with high-volume metastatic disease, while abiraterone also shows similar benefits in high-risk patients, indicating both treatments are effective options alongside ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline. Morris, MJ., Rumble, RB., Basch, E., et al.[2019]

In a study of 773 men with metastatic hormone-sensitive prostate cancer, the combination of docetaxel and androgen deprivation therapy (ADT) showed similar progression-free survival (PFS) and overall survival (OS) benefits across different age groups, indicating its efficacy regardless of age.

Older men (over 70 years) experienced a modest increase in the number of adverse events compared to younger men, suggesting that while the treatment is effective, careful consideration of potential side effects is crucial for older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Adverse Events of Docetaxel for Metastatic, Hormone-sensitive Prostate Cancer Among Elderly Men: A Post Hoc Analysis of the CHAARTED Trial. Li, EV., Siddiqui, MR., Weiner, AB., et al.[2022]

Cabazitaxel, abiraterone, and enzalutamide have been shown to significantly prolong overall survival in men with metastatic castration-resistant prostate cancer who have previously undergone chemotherapy, based on randomized phase 3 clinical trials.

The introduction of these new treatments has led to their approval and reimbursement in Belgium, marking an important advancement in options for patients with docetaxel-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New treatments for castration-resistant prostate cancer]. Sautois, B., Gennigens, C.[2021]

A systematic review of 6067 patients from five trials found that both abiraterone acetate plus ADT (Abi-ADT) and docetaxel plus ADT (Doce-ADT) significantly improved overall survival compared to ADT alone, with hazard ratios of 0.63 and 0.75 respectively.

There was no statistically significant difference in overall survival between Abi-ADT and Doce-ADT, but Bayesian analysis suggested an 89% probability that Abi-ADT might be the preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis. Wallis, CJD., Klaassen, Z., Bhindi, B., et al.[2019]

In a study of 196 men with metastasized hormone-sensitive prostate cancer, the combination of abiraterone acetate (AA) and androgen deprivation therapy (ADT) showed significantly longer progression-free survival (PFS1: 23 months vs. 13 months) and overall survival (OS: 80 months vs. 61 months) compared to docetaxel (D) and ADT.

Both treatment regimens had similar overall toxicity rates, suggesting that while AA+ADT may offer better progression-free outcomes, it does not increase the risk of adverse effects compared to D+ADT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer. Tsaur, I., Heidegger, I., Bektic, J., et al.[2022]

Abiraterone is considered a cost-effective treatment for metastatic castration-resistant prostate cancer (mCRPC) at $94,000 per quality-adjusted life year (QALY) compared to placebo, based on a decision-tree model analyzing various treatment options over 18 months.

Cabazitaxel, while effective, is not cost-effective compared to abiraterone, with an incremental cost-effectiveness ratio of $956,000 per QALY, indicating that it may not be a viable option for patients after docetaxel failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis. Zhong, L., Pon, V., Srinivas, S., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Adverse Events of Docetaxel for Metastatic, Hormone-sensitive Prostate Cancer Among Elderly Men: A Post Hoc Analysis of the CHAARTED Trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Effect of Adding Docetaxel to Androgen-Deprivation Therapy in Patients With High-Risk Prostate Cancer With Rising Prostate-Specific Antigen Levels After Primary Local Therapy: A Randomized Clinical Trial. [2022]

4. Belgium pubmed.ncbi.nlm.nih.gov

[New treatments for castration-resistant prostate cancer]. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of docetaxel for castration-sensitive prostate cancer in a real-world population-based analysis. [2021]