Hormone Therapy Break for Metastatic Prostate Cancer

(A-DREAM Trial)

Not currently recruiting at 351 trial locations

Overseen By Atish D. Choudhury, MD, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: LHRH agonist, ARPI

Must not be taking: Experimental agents

Disqualifiers: Surgical castration, Active second 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 18

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether men with metastatic prostate cancer, who have responded well to intense antiandrogen therapy (a type of hormone therapy), can pause their hormone treatments. The goal is to determine if stopping these medications allows testosterone levels to recover without the cancer returning. Suitable candidates for this trial include patients who have received consistent hormone therapy for about 18 to 24 months and have not experienced cancer spread to the liver or brain. Participants will stop their medications and undergo monitoring for any signs of cancer recurrence. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial involves taking a break from hormonal medications for prostate cancer if your doctor advises it. This means you might stop taking your current medications temporarily, but it depends on your doctor's guidance.

Is there any evidence suggesting that antiandrogen therapy interruptions are likely to be safe for patients with metastatic prostate cancer?

Research has shown that antiandrogen therapy, a common treatment for prostate cancer, is usually well-tolerated by patients. One study found that this therapy lowered prostate-specific antigen (PSA) levels in over 90% of patients, indicating good cancer control. Another study noted that patients using similar treatments experienced longer periods without worsening cancer symptoms.

However, like any treatment, side effects can occur. Some people may notice changes in energy, mood, or sexual function, but these are often manageable. Researchers closely monitor participants in trials like this one to ensure their safety.

In summary, while antiandrogen therapy can have some side effects, previous studies generally consider it safe. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about the hormone therapy break for metastatic prostate cancer because it offers a potential shift from the continuous hormonal treatments that are standard today. Typically, treatments involve ongoing antiandrogen therapy to lower testosterone and block hormone signals, but this trial explores discontinuing these medications temporarily. This approach could reduce side effects and improve quality of life for patients while still effectively managing cancer. By closely monitoring patients and resuming treatment only if necessary, this method could personalize and potentially enhance the overall treatment strategy for prostate cancer.

What evidence suggests that this treatment might be an effective treatment for metastatic prostate cancer?

Research has shown that antiandrogen therapy effectively treats prostate cancer that has spread and still responds to hormones. Specifically, drugs like abiraterone, enzalutamide, and apalutamide significantly lower and stabilize PSA levels, which monitor prostate cancer. These treatments can help control cancer growth. In this trial, participants will discontinue hormonal medications as part of the treatment arm, which may help manage the side effects of ongoing treatment while still controlling the cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Atish D. Choudhury, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men with metastatic hormone-sensitive prostate cancer who have responded well to intense antiandrogen therapy. They must not have liver or brain metastases, should be on continuous testosterone suppression for 18-24 months, and treated with ARPIs like abiraterone or enzalutamide for at least a year. Men can't join if they're very sick (ECOG 0-2), have high PSA levels, are hypogonadal before treatment, or had surgical castration.

Inclusion Criteria

My scans showed cancer spread before starting hormone therapy.

I am on hormone therapy for cancer using specific medications.

Radiographic evidence of disease is not required at the time of enrollment

Exclusion Criteria

I do not have an active second cancer, except for certain skin or superficial bladder cancers.

My PSA level is 5 ng/ml or higher before starting intense hormone therapy.

Testosterone < 50 ng/dl at time of enrollment to A032101

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Interruption

Patients stop both hormonal medications and are monitored for symptoms

18 months

Follow-up every 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Antiandrogen Therapy

Trial Overview The A-DREAM trial is testing whether patients with advanced prostate cancer can safely take breaks from their hormonal medications after responding exceptionally well to them. It involves stopping the usual drugs that lower testosterone and block male hormones in cancer cells under doctor supervision to see if this allows natural testosterone recovery without worsening the disease.

How Is the Trial Designed?

Group I: Treatment (discontinue hormonal medication, follow up) Experimental Treatment 4 Interventions

Patients stop both hormonal medications (medication to decrease testosterone levels in the body and potent oral hormonal medication to block growth signals from male hormones in the cancer cells). Patients are then followed every 12 months for symptoms. Patients with an increase in PSA level to greater than or equal to 5 ng/ml, changes on imaging studies suggesting that their cancer is growing back, or symptoms that the doctor thinks is related to their cancer growing back, resume both hormonal treatments.

Antiandrogen Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Antiandrogen Therapy for:

• Prostate cancer

Approved in European Union as Antiandrogen Therapy for:

• Prostate cancer

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Androgen deprivation therapy (ADT) is effective for managing metastatic or recurrent prostate cancer but can lead to significant side effects, including changes in body composition, increased fracture risk, and insulin resistance.

Recent studies suggest that denosumab and toremifene citrate can help reduce fracture risk in men undergoing ADT, highlighting the importance of managing these adverse effects to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen deprivation therapy in prostate cancer: anticipated side-effects and their management. Kim, HS., Freedland, SJ.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7076308/

Efficacy of Androgen Deprivation Therapy in Patients with ... The purpose of this study was to determine the comparative effectiveness of androgen deprivation therapy (ADT) combined with docetaxel (DTX)-based chemotherapy

2. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433126

Balancing Hormone Therapy: Mitigating Adverse Effects of ... Five-year follow-up analyses demonstrated that 34% of the metastasis-directed therapy (MDT) group remain ADT-free at 5 years, in contrast to 8% ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3172154/

Novel Androgen Deprivation Therapy (ADT) in the ... This study showed better PSA and objective response in patients who had upfront anti-androgen withdrawal and ketoconazole use compared to those who underwent ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124000282

A 3-year Interim Analysis of the Observational J-ROCK Study In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone- ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1324181/full

Comparative effectiveness of multiple androgen receptor ... Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than ...

6. icer.org icer.org/wp-content/uploads/2020/10/ICER_Prostate_Cancer_Final_Evidence_Report_100418.pdf

Antiandrogen Therapies for Nonmetastatic Castration- ... 11 Time to symptomatic progression was also longer with apalutamide (HR 0.45; 95%. CI 0.32 to 0.63) and there were improvements in PFS and PSA progression.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4094624/

Androgen deprivation therapy for prostate cancer: long-term ... ADT can normalize serum prostate specific antigen in over 90% of patients and results in sizable tumor response in 80% to 90%. This treatment can be done either ...

8. urotoday.com urotoday.com/library-resources/mhspc/147798-the-current-state-of-treatment-implementation-for-mhspc-in-north-america.html

The Current State of Treatment Implementation for ... Treatment trends over time did demonstrate an overall decrease in ADT only (66% to 60%) or ADT + non-steroidal anti-androgen (31% to 17%) utilization between ...