Neoadjuvant and Adjuvant Abiraterone + Apalutamide for Prostate Cancer

No longer recruiting at 3 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Antiandrogens, CYP17 inhibitors

Disqualifiers: Cardiovascular disease, Seizure history, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a combination of medications, including Abiraterone and Apalutamide (both hormone therapies), on localized prostate cancer. Researchers aim to assess how these drugs affect cancer cells before and after surgery and whether they improve outcomes. The trial includes different groups: some participants receive medications before surgery, some after, and one group is observed without intervention. Men with biopsy-confirmed prostate cancer and no signs of spreading might be suitable candidates, especially if their cancer has certain characteristics, such as a high Gleason score, which measures cancer aggressiveness. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications known to lower the seizure threshold at least one week before starting the study treatment. If you are on such medications, you may need to discontinue or substitute them.

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

Research has shown that the treatment combinations in this trial have been well-tolerated in past studies. Abiraterone acetate and prednisone, when used together, have been safely used for prostate cancer, with studies indicating that patients generally handle this combination well and manage side effects effectively.

One study found that adding apalutamide to abiraterone acetate and prednisone also maintained a good safety record, meaning most people do not experience severe side effects. Leuprolide, a hormone therapy, is commonly used and generally safe, though it can cause mild side effects like tiredness or hot flashes.

Overall, these treatments have been used safely in other settings, and previous patients have tolerated them well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine Abiraterone Acetate and Apalutamide in a new approach to managing prostate cancer. Unlike the standard of care that often includes surgery, radiation, or traditional hormone therapies, this combination targets and blocks androgen receptors more effectively, potentially reducing tumor growth more efficiently. By adding Apalutamide, which directly inhibits the androgen receptor signaling, this regimen may offer a more comprehensive attack on cancer cells. This approach aims to improve patient outcomes by possibly delaying disease progression and enhancing survival rates.

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

Research has shown that combining abiraterone acetate with hormone therapy (also known as androgen deprivation therapy or ADT) can greatly benefit prostate cancer patients. Specifically, using abiraterone with ADT increased the survival rate after three years by 7% compared to ADT alone. In this trial, participants in Arm 1A and Arm 2A will receive a combination of abiraterone acetate, apalutamide, leuprolide, and prednisone. Adding apalutamide to abiraterone has proven effective for patients with high-risk prostate cancer by improving PSA levels and controlling disease spread as seen in scans. Patients using these combinations have experienced longer survival and slower cancer progression. These findings suggest that these treatments could effectively manage prostate cancer that has not spread beyond the prostate. ^{2 3 6 7 8}

Who Is on the Research Team?

Mary-Ellen Taplin, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Men over 18 with confirmed prostate adenocarcinoma, eligible for surgery, and no metastatic disease. They must have a Gleason score of at least 7 or higher PSA/T3 disease, good organ/marrow function, and agree to use contraception. Excluded if they've had prior hormone therapy for prostate cancer (except certain inhibitors), severe liver impairment, conditions requiring high-dose steroids, or significant cardiovascular issues.

Inclusion Criteria

I am eligible for prostate removal surgery as per my doctor's assessment.

Lymph nodes must be less than 20 mm in the short (transverse) axis

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 hormone therapy for prostate cancer, but not specific treatments.

Hypogonadism or severe androgen deficiency as defined by screening serum testosterone

I have received treatments like chemotherapy, radiation, or immunotherapy for prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant therapy with abiraterone acetate, apalutamide, leuprolide, and prednisone for 6 months before radical prostatectomy

6 months

Radical Prostatectomy

Participants undergo radical prostatectomy after completing neoadjuvant therapy

1 day

1 visit (in-person)

Adjuvant Treatment

Participants receive adjuvant therapy with abiraterone acetate, apalutamide, leuprolide, and prednisone for 12 months or are observed

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with quality of life assessments at 6, 12, and 24 months post-RP

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone Acetate
• Apalutamide
• Leuprolide
• Prednisone

Trial Overview

The trial is testing the combination of Abiraterone Acetate and Apalutamide with Leuprolide and Prednisone in men undergoing prostatectomy for localized prostate cancer. It aims to see how this intense hormone treatment affects surgical outcomes and cancer markers.

How Is the Trial Designed?

Group I: Arm 2A: AAPL Adjuvant Therapy [Part 2] Experimental Treatment 4 Interventions

Eligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 12 months

Group II: Arm 1B: APL Neoadjuvant Therapy [Part 1] Experimental Treatment 3 Interventions

Eligible Participants will be randomized to receive: APL: Abiraterone acetate (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/day orally) for 6 months

Group III: Arm 1A: AAPL Neoadjuvant Therapy [Part 1] Experimental Treatment 4 Interventions

Eligible Participants will be randomized to receive: AAPL: Abiraterone acetate (240 mg/day orally), Apalutamide (1000 mg/day orally), Leuprolide (22.5 mg every 12 weeks intramuscularly), Prednisone (5 mg/twice daily orally) for 6 months Pts x weeks to RP

Group IV: Arm 2B: Observation [Part 2] Active Control 1 Intervention

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

The study evaluated the effectiveness of abiraterone acetate combined with prednisone (AA+P) in 53 patients with castration-resistant prostate cancer (mCRPC), showing a good response to this treatment.

Key factors associated with higher survival rates included a longer duration of prostate cancer prior to treatment, lower pain intensity, extended treatment duration with AA+P, and favorable tumor marker levels at 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Metastatic Castration-resistant Prostate Cancer Patients With Abiraterone Acetate and Prednisone and Corresponding Survival Prognostic Factors. Jimenez Romero, ME., Gallego, MC., Navarro Serrato, JC., et al.[2021]

In a phase 3 trial involving 1199 patients, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly improved overall survival, with a median survival not reached in the abiraterone group compared to 34.7 months in the placebo group.

The study also showed that patients receiving abiraterone had a median radiographic progression-free survival of 33.0 months, compared to 14.8 months in the placebo group, indicating a strong benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi, K., Tran, N., Fein, L., et al.[2022]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

In a study of 131 patients with high-risk, nonmetastatic, castration-resistant prostate cancer, treatment with abiraterone acetate and prednisone resulted in an impressive 86.9% of patients achieving a 50% or greater reduction in prostate-specific antigen (PSA) levels, indicating strong efficacy.

The treatment also showed promising secondary outcomes, with a median time to PSA progression of 28.7 months, while safety was generally acceptable, although 96.2% of patients experienced adverse events, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The IMAAGEN Study: Effect of Abiraterone Acetate and Prednisone on Prostate Specific Antigen and Radiographic Disease Progression in Patients with Nonmetastatic Castration Resistant Prostate Cancer. Ryan, CJ., Crawford, ED., Shore, ND., et al.[2021]

In a study involving 202 patients with metastatic castration-resistant prostate cancer, the sequence of treatment with abiraterone acetate followed by enzalutamide resulted in a longer time to second PSA progression (19.3 months) compared to the reverse sequence (15.2 months), indicating a more effective treatment strategy.

Enzalutamide demonstrated a significantly higher PSA response rate (36%) as a second-line therapy compared to abiraterone (4%), suggesting that enzalutamide is more effective when used after abiraterone in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal sequencing of enzalutamide and abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer: a multicentre, randomised, open-label, phase 2, crossover trial. Khalaf, DJ., Annala, M., Taavitsainen, S., et al.[2021]

In a phase 3 trial with 1088 patients, abiraterone acetate plus prednisone significantly improved overall survival compared to placebo plus prednisone, with a median survival of 34.7 months versus 30.3 months, indicating its efficacy in treating chemotherapy-naive castration-resistant prostate cancer.

The treatment was associated with a manageable safety profile, although there were some increased risks of grade 3-4 adverse events, such as cardiac disorders and elevated liver enzymes, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Ryan, CJ., Smith, MR., Fizazi, K., et al.[2022]

In a study of 133 patients with non-metastatic castration-resistant prostate cancer, abiraterone acetate (AA) plus prednisone showed comparable overall survival and cancer-specific survival to enzalutamide (Enz) over a median follow-up of 36 months.

However, patients treated with AA plus prednisone had a significantly higher risk of non-cancer-caused death compared to those treated with Enz, suggesting that while both treatments are effective, AA plus prednisone may pose additional safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. Tsujino, T., Tokushige, S., Komura, K., et al.[2023]

In a study of 254 metastatic castration-resistant prostate cancer patients treated with abiraterone acetate plus prednisone (AA+P) over a median follow-up of 67.1 weeks, patient-reported outcomes (PROs) showed no significant decline in quality of life or cognitive function, indicating that the treatment is well-tolerated.

The study also reported a 66.4% response rate in prostate-specific antigen (PSA) levels, demonstrating the efficacy of AA+P in managing this patient population while maintaining their overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence in patient-reported outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate + prednisone (AA+P) across Canada: Final results of COSMiC. Gotto, G., Drachenberg, DE., Chin, J., et al.[2020]

Abiraterone acetate (AA) is effective and well tolerated in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC), showing a 49% rate of PSA decline of 50% or more at 12 weeks in a study of 145 patients.

The median progression-free survival was 17 months and overall survival was 26.5 months, with outcomes significantly influenced by factors such as pain presence, patient satisfaction, and PSA levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abiraterone acetate in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: an Italian multicenter "real life" study. Cindolo, L., Natoli, C., De Nunzio, C., et al.[2022]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a study of 1199 men with metastatic castration-sensitive prostate cancer, treatment with abiraterone acetate plus prednisone (AA+P) significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) compared to placebo, particularly in patients with lung metastases.

Patients with visceral metastases (VM) who received AA+P had a median OS of 55.4 months versus 33.0 months for those on placebo, and a median rPFS of 30.7 months compared to 18.3 months, indicating that AA+P is an effective treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of abiraterone acetate plus prednisone in patients with castration-sensitive prostate cancer and visceral metastases over four years of follow-up: A post-hoc exploratory analysis of the LATITUDE study. Baciarello, G., Özgüroğlu, M., Mundle, S., et al.[2022]

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