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

50 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Apalutamide for prostate cancer?

Apalutamide has been shown to significantly improve survival and delay disease progression in patients with different types of prostate cancer, such as metastatic castration-sensitive and non-metastatic castration-resistant prostate cancer, when combined with androgen deprivation therapy. It has also been effective in maintaining quality of life and is generally well tolerated. ^{1 2 3 4 5}

Is Apalutamide safe for use in humans?

The studies reviewed focus on the safety of different surgical methods for prostate cancer, such as robot-assisted radical prostatectomy (RARP), and suggest that RARP is a safe option for men with high-risk prostate cancer. However, they do not provide specific safety data on Apalutamide itself. ^{6 7 8 9 10}

How is the drug apalutamide used before surgery for prostate cancer different from other treatments?

Apalutamide is unique because it is an oral drug that specifically targets androgen receptors, which are proteins that help prostate cancer cells grow. This drug is typically used for advanced prostate cancer, but using it before surgery for prostate cancer is a novel approach that may help shrink tumors and improve surgical outcomes. ^{1 2 3 11 12}

What is the purpose of this trial?

This phase II trial studies how well apalutamide works in treating patients with prostate cancer before radical prostatectomy. Androgen can cause the growth of prostate cancer cells. Hormone therapy using apalutamide may fight prostate cancer by lowering the amount of androgen the body makes and may make it less likely for patients to receive radiation therapy after surgery.

Research Team

John W Davis

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. [2019]

3. United States 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. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. [2021]

6. India pubmed.ncbi.nlm.nih.gov

Perioperative adverse events and functional outcomes following open and robot-assisted prostatectomy in patients over age 70. [2021]

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

Long-term adverse effects after retropubic and robot-assisted radical prostatectomy. Nationwide, population-based study. [2021]

8. England pubmed.ncbi.nlm.nih.gov

How does robot-assisted radical prostatectomy (RARP) compare with open surgery in men with high-risk prostate cancer? [2013]

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

Is robot-assisted radical prostatectomy safe in men with high-risk prostate cancer? Assessment of perioperative outcomes, positive surgical margins, and use of additional cancer treatments. [2022]

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

Robotic vs. Retropubic radical prostatectomy in prostate cancer: A systematic review and an meta-analysis update. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Prospects of Treating Prostate Cancer through Apalutamide: A Mini-Review. [2022]