Apalutamide Before Surgery for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiandrogens, Estrogens, LHRH agonists

Disqualifiers: Hypertension, Heart disease, Liver disease, 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: 24 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment plan for prostate cancer using a drug called apalutamide (also known as Erleada) before surgery. The goal is to determine if this drug can reduce androgen levels, potentially slowing cancer cell growth and decreasing the need for radiation therapy after surgery. Men diagnosed with intermediate-risk prostate cancer who plan to undergo prostate removal may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications that affect hormone levels or have a history of seizures, you may need to discuss this with the trial team.

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

Research shows that apalutamide is generally safe for patients. Studies have found it to be well-tolerated in both clinical trials and real-world settings. For instance, one study found that most patients did not experience serious side effects. However, rare cases of serious events, such as strokes, occurred in 0.2% of patients.

The FDA has already approved apalutamide for other types of prostate cancer, indicating it has passed safety checks for those conditions. This approval might reassure participants about its safety for use before surgery in this trial. Discuss any concerns or specific conditions with the trial team to ensure it’s a good fit. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about using apalutamide before surgery for prostate cancer because it offers a unique approach to treatment. Unlike standard treatments that often involve surgery or radiation as initial steps, apalutamide is an oral medication that targets androgens, which are hormones that can promote the growth of prostate cancer cells. This drug works by blocking the androgen receptors, potentially shrinking the tumor before surgery. This pre-surgical strategy could make the surgical removal of cancer more effective and may reduce the risk of cancer spreading, offering a new layer of hope for better outcomes in prostate cancer treatment.

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

Research has shown that apalutamide effectively treats prostate cancer by lowering levels of certain hormones that promote cancer growth. Studies have demonstrated that apalutamide significantly reduces the risk of death in prostate cancer patients. One study found that, when combined with other treatments, apalutamide greatly improved survival rates compared to a placebo. Another study showed it caused a sharp drop in PSA levels, which monitor prostate cancer. In this trial, participants will receive apalutamide before undergoing radical prostatectomy, making it a promising option for slowing down prostate cancer before surgery. ^{2 5 6 7 8}

Who Is on the Research Team?

John W Davis

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Men with intermediate-risk prostate cancer, suitable for surgery, and no metastases. They must have a testosterone level above 200 ng/mL, agree to use contraception during the trial and for 3 months after, be able to swallow tablets, and not have other serious health issues or another active malignancy.

Inclusion Criteria

My scans show no signs of cancer spread, and any suspicious lymph nodes are smaller than 10 mm.

Serum bilirubin < 1.5 x upper limit of normal (ULN); Note: In subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible

Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria

I have had serious heart issues like a heart attack or severe heart failure recently.

My high blood pressure is under control with medication.

Severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apalutamide orally daily for 24 weeks prior to radical prostatectomy

24 weeks

Surgery

Participants undergo radical prostatectomy within 2 weeks of completing apalutamide treatment

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including biochemical recurrence and quality of life assessments

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide
• Radical Prostatectomy

Trial Overview The trial is testing apalutamide's effectiveness in treating prostate cancer before surgical removal of the prostate. Apalutamide is a hormone therapy that lowers androgen levels which may reduce the need for radiation post-surgery.

How Is the Trial Designed?

Group I: Treatment (apalutamide, radical prostatectomy) Experimental Treatment 3 Interventions

Patients receive apalutamide PO daily for 24 weeks in the absence of disease progression or unacceptable toxicity. Within 2 weeks of completing apalutamide, patients undergo radical prostatectomy.

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

Approved in United States as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[2021]

In a study of 251 elderly men (≥70 years old) who underwent either open retropubic radical prostatectomy (ORRP) or robot-assisted radical prostatectomy (RARP), the rates of major complications were similar for both surgical methods, at 4.7% for ORRP and 4.9% for RARP.

Both surgical approaches resulted in comparable continence rates after 24 months (78.5% for ORRP vs. 79.4% for RARP), but the rates of erectile function remained low, indicating that while safety is similar, functional outcomes may still be a concern for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative adverse events and functional outcomes following open and robot-assisted prostatectomy in patients over age 70. Sancı, A., Özkaya, MF., Oguz, ES., et al.[2021]

In a study involving 57 patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of apalutamide with abiraterone acetate and prednisone was well tolerated and demonstrated significant antitumor activity, particularly in patients who had not previously been treated with androgen receptor inhibitors.

While apalutamide reduced the systemic exposure to prednisone by 61%, no significant adverse events related to mineralocorticoid excess were observed, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study. Posadas, EM., Chi, KN., de Wit, R., et al.[2021]

Apalutamide, an oral medication for non-metastatic castration-resistant prostate cancer, can cause a range of skin reactions, including a rare lichenoid reaction, as demonstrated in a case study of a patient after 4 months of treatment.

This case highlights the importance of a multidisciplinary approach in identifying and managing drug-related adverse events, which can improve diagnosis and treatment strategies for patients experiencing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. Cremante, M., Puglisi, S., Gandini, A., et al.[2023]

A study comparing 177 patients who underwent open retropubic radical prostatectomy (RRP) and 233 patients who had robot-assisted radical prostatectomy (RARP) found no significant differences in cancer recurrence rates or positive margin rates, indicating that RARP is a safe and effective option for high-risk prostate cancer patients.

Patients who underwent RARP experienced less blood loss and were more likely to have complete bilateral nerve-sparing procedures compared to those who had open RRP, suggesting additional benefits of the robotic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How does robot-assisted radical prostatectomy (RARP) compare with open surgery in men with high-risk prostate cancer? Punnen, S., Meng, MV., Cooperberg, MR., et al.[2013]

In the SPARTAN trial, apalutamide significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen-deprivation therapy, demonstrating its efficacy as a treatment option.

Apalutamide was generally well tolerated, with fatigue being the most common side effect, indicating a favorable safety profile while maintaining health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Al-Salama, ZT.[2020]

The SAVE trial is a Phase II study involving 202 men with advanced prostate cancer, comparing the effects of apalutamide combined with salvage radiotherapy against androgen-deprivation therapy plus salvage radiotherapy.

The primary goal is to evaluate sexual function after nine months of treatment, while also assessing quality of life, safety, and short-term efficacy of apalutamide, highlighting its potential benefits in managing prostate cancer post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. Dirix, P., Strijbos, M., den Mooter, TV., et al.[2021]

Apalutamide is an oral androgen receptor inhibitor that effectively blocks androgen effects, and it received its first global approval in February 2018 for treating non-metastatic castration-resistant prostate cancer (nmCRPC).

Currently, apalutamide is being tested in phase III trials for various prostate cancer stages, including metastatic castration-resistant prostate cancer and high-risk localized prostate cancer, indicating its potential for broader applications in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. Al-Salama, ZT.[2019]

Citations

1. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

2. erleadahcp.com erleadahcp.com/efficacy/

Efficacy | ERLEADA® (apalutamide) HCP Median follow-up time was 44.0 months. 1. The survival rate at 48 months was 65.1% for ERLEADA ® + ADT patients vs 51.8% for placebo + ADT patients.

3. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51– ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39893578/

Real-world clinical usage and efficacy of apalutamide in ... The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124002530

Apalutamide in Metastatic Castration-sensitive Prostate ... Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

6. erleadahcp.com erleadahcp.com/patient-reported-outcomes/

PATIENT-REPORTED OUTCOMES FOR HRQoL 1-6 Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA® and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39613567/

Results from the Multicenter Real-world ARON-3 Study Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1903307

Apalutamide for Metastatic, Castration-Sensitive Prostate ... In our trial, initial therapy with apalutamide in patients with metastatic, castration-sensitive prostate cancer led to improved clinical outcomes. The intent ...