ADT + Radiation +/- Abiraterone & Apalutamide for Prostate Cancer

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: GnRH agonists

Must not be taking: CYP3A4 inhibitors, CYP2D6 substrates

Disqualifiers: Seizure, Uncontrolled hypertension, Active infection, 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: 3

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two different drug combinations used with radiation to treat prostate cancer when PSA levels rise after surgery. The goal is to determine which combination more effectively manages the condition. Participants should have confirmed prostate cancer, a rising PSA level post-surgery, and be candidates for radiation and hormone therapy. Individuals who have undergone prostate surgery and experience increasing PSA levels might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants the chance to contribute to significant advancements in prostate cancer treatment.

Do I need to stop taking my current medications for the trial?

The trial requires that you stop taking medications known to lower the seizure threshold and CYP3A4 inhibitors or inducers and CYP2D6 substrates at least 4 weeks before starting. If you're on these medications, you'll need to discuss alternatives with your doctor.

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

Research shows that treatment using GnRH (a hormone) and Bicalutamide is generally well-tolerated. Studies indicate that GnRH treatments are linked to fewer serious heart issues compared to other options, though they may still cause side effects like hot flashes and reduced interest in sex.

For the other treatment option, which includes GnRH, Abiraterone, Apalutamide, and Prednisone, studies have shown it to be safe for previous patients. This combination has successfully improved prostate cancer outcomes without affecting quality of life. Common side effects might include fatigue and joint pain. Both treatments have been tested in other settings, suggesting they are generally safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they explore new combinations of drugs that could enhance existing therapies. The treatment with GnRH + Bicalutamide is unique because it combines hormone therapy with salvage radiation, potentially improving outcomes by reducing testosterone, which fuels cancer growth, more effectively. The second approach, using GnRH with Abiraterone, Apalutamide, and Prednisone, adds two newer agents that block androgen receptors and further lower androgen levels, which could lead to better cancer control. These combinations aim to tackle prostate cancer from multiple angles, offering hope for improved effectiveness over standard hormone therapies alone.

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

This trial will compare two treatment approaches for advanced prostate cancer. One group of participants will receive a combination of a GnRH agonist and bicalutamide. Studies have shown that this combination can delay cancer progression and improve quality of life by reducing symptoms. Another group will receive a mix of GnRH, abiraterone, prednisone, and apalutamide. Research indicates that this combination also improves outcomes by significantly extending the time before the disease worsens and increasing overall survival rates. Evidence supports both treatment approaches as effective in managing prostate cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Paul Nguyen, MD

Principal Investigator

Dana-Farber/Brigham and Women's Cancer Center

Are You a Good Fit for This Trial?

Men aged 18-95 with prostate cancer who've had surgery but now have rising PSA levels. They must have a Gleason score of 8-10, fast PSA doubling time, and good organ function. Men must agree to use contraception and not donate sperm during the study.

Inclusion Criteria

I can swallow pills.

My PSA level is 0.1 or higher after prostate surgery, and I have at least one risk factor.

Ability to understand and comply with study procedures

Exclusion Criteria

I haven't had a major heart problem in the last 6 months.

I do not have uncontrolled high blood pressure, serious gut problems, ongoing infections, or conditions needing high-dose steroids.

I am not currently being treated for another cancer nor at high risk of cancer returning within 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GnRH agonist injections and either Bicalutamide or Abiraterone acetate, Apalutamide, and Prednisone, along with salvage radiation therapy

6 months

Monthly or every 3 months for injections

Follow-up

Participants are monitored for safety, effectiveness, and survival outcomes after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• Apalutamide
• Bicalutamide
• GnRH
• Prednisone
• Salvage radiation

Trial Overview The trial is testing two ADT combinations with radiation for prostate cancer patients post-surgery with rising PSA. It's seeing if adding Abiraterone and Apalutamide to standard treatment offers better outcomes.

How Is the Trial Designed?

Group I: GnRH+Abiraterone+Apalutamide+Prednisone Experimental Treatment 5 Interventions

* GnRH agonist injection monthly or every 3 months for 6 months * Abiraterone acetate by mouth once/day for 6 months * Prednisone by mouth once/day for 6 months * Apalutamide by mouth once/day for 6 months * Salvage radiation (starting 4-10 weeks after initiation of ADT)

Group II: GnRH + Bicalutamide Experimental Treatment 3 Interventions

* GnRH agonist injection monthly or every 3 months for 6 months * Bicalutamide by mouth once/day for 6 months * Salvage radiation (starting 4-10 weeks after initiation of ADT)

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

Approved in European Union as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Casodex for:

• Metastatic prostate cancer

Approved in Japan as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Janssen Pharmaceutica

Industry Sponsor

Trials

43

Recruited

9,200+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Immunology Treatments

Top Products

Stelara (ustekinumab), Darzalex (daratumumab), Remicade (infliximab), Tremfya (guselkumab)

Published Research Related to This Trial

Bicalutamide is a newly approved non-steroidal anti-androgen for prostate cancer treatment, showing strong affinity for androgen receptors and effective tumor suppression in pharmacological studies, leading to its approval in about 70 countries.

In a late Phase II study in Japan, bicalutamide achieved a response rate of 64.4% when used alone, highlighting its potential as a standalone treatment option that may enhance patient quality of life and sexual function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A new anti-androgen, bicalutamide (Casodex), for the treatment of prostate cancer--basic clinical aspects]. Akaza, H.[2014]

A combination treatment of 150 mg bicalutamide and 5 mg finasteride was effective in achieving undetectable PSA levels and improving quality of life in a 69-year-old patient with relapsed prostate cancer, demonstrating minimal side effects.

Laboratory experiments showed that this combination therapy inhibited cancer cell proliferation and reduced androgen receptor activity, potentially slowing the progression to hormone independence in prostate cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The biological basis for the use of an anti-androgen and a 5-alpha-reductase inhibitor in the treatment of recurrent prostate cancer: Case report and review. Wang, LG., Mencher, SK., McCarron, JP., et al.[2014]

In a study of 813 patients with metastatic prostate cancer, bicalutamide combined with LHRH-A therapy showed longer median times to progression (97 weeks) and death (180 weeks) compared to flutamide combined with LHRH-A (77 weeks and 148 weeks, respectively).

Both treatments were generally well tolerated, but bicalutamide had a lower incidence of diarrhea and fewer withdrawals due to side effects compared to flutamide, which had a significantly higher incidence of diarrhea (26% vs. 12%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group. Schellhammer, PF., Sharifi, R., Block, NL., et al.[2019]

In a study of 6882 men with high-risk prostate cancer, the type of androgen suppression therapy (AST) used alongside radical radiotherapy (RRT) significantly influenced the risk of prostate cancer death, particularly when comparing combinations of bicalutamide and GnRH with different RRT types.

Men receiving monotherapy with bicalutamide combined with conventional fractionated external beam radiotherapy (CF-EBRT) had a notably higher risk of prostate cancer death (HR 2.35), while those treated with neoadjuvant CAB/adjuvant GnRH showed no increased risk, indicating the importance of therapy combinations in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists. Bonde, TM., Garmo, H., Stattin, P., et al.[2023]

In a phase I study involving patients with advanced prostate cancer, irradiation to the testes was tested as an alternative to standard androgen deprivation treatments, showing that both tested radiation regimens (17 Gy in 2 fractions and 24 Gy in 3 fractions) were well tolerated with minimal toxicity.

Despite the treatment being well tolerated, neither radiation regimen successfully induced castration, as all patients maintained normal testosterone levels during the 11 to 36 months of follow-up, indicating that further research is needed to determine the efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective phase I study on testicular castration induced by radiation treatment. Faria, S., Cury, F., Souhami, L.[2018]

Bicalutamide, particularly at a 150-mg daily dose, is effective as a monotherapy for locally advanced prostate cancer, providing similar survival outcomes to castration, while also improving quality of life.

When combined with a luteinizing hormone-releasing hormone agonist (LHRH-A), a lower 50-mg daily dose of bicalutamide shows equivalent efficacy to flutamide, with the added benefit of better tolerability and longer median survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bicalutamide (Casodex) in the treatment of prostate cancer: history of clinical development. Kolvenbag, GJ., Blackledge, GR., Gotting-Smith, K.[2022]

In a study of 318 prostate cancer patients with a median follow-up of 56 months, both radiotherapy combined with GnRHa and radiotherapy combined with bicalutamide showed similar five-year biochemical relapse-free survival rates (85.5% for GnRHa and 88.3% for bicalutamide).

Bicalutamide may be a suitable alternative for patients who prefer to avoid the side effects associated with GnRHa, highlighting the need for further randomized trials to compare these two treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy Plus GnRH Analogue Versus High Dose Bicalutamide: A Case Control Study. Buwenge, M., Deodato, F., Macchia, G., et al.[2020]

Bicalutamide, when used in conjunction with radiation therapy, showed cytotoxic effects in androgen-dependent prostate cancer cells (LNCaP), leading to cell cycle arrest and reduced expression of prostate serum antigen (PSA) and androgen receptor (AR).

The study found that bicalutamide decreased the effectiveness of radiation in LNCaP cells, suggesting that it should not be administered close to radiation treatment to avoid antagonistic interactions, while showing an additive effect in androgen-independent DU145 cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonistic interaction between bicalutamide (Casodex) and radiation in androgen-positive prostate cancer LNCaP cells. Quéro, L., Giocanti, N., Hennequin, C., et al.[2014]

In a randomized trial involving 813 patients with Stage D2 prostate carcinoma, bicalutamide combined with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy showed equivalent efficacy to flutamide combined with LHRH-A, with similar time to disease progression over a median follow-up of 95 weeks.

The analysis indicated that both treatment regimens had comparable outcomes, with a hazard ratio of 0.9, suggesting that bicalutamide is as effective as flutamide in delaying disease progression in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Schellhammer, PF., Sharifi, R., Block, NL., et al.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5086

Abiraterone with discontinuation of gonadotropin-releasing ... We present a single arm, phase II trial of pts with metastatic PC treated with AA+Prednisone (AAP) after GnRH discontinuation.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12554570/

Efficacy and safety of apalutamide, abiraterone acetate ... This study analyzed 146 mHSPC patients. The results are displayed that Apalutamide and Abiraterone significantly prolonged PFS and PSA-PFS ...

3. targetedonc.com targetedonc.com/view/abiraterone-prednisone-apalutamide-improves-prostate-cancer-outcomes-leaves-hrqol-unaffected

Abiraterone, Prednisone, Apalutamide Improves Prostate ... Oncological outcomes improved with the addition of abiraterone acetate (Zytiga) plus prednisone (AAP) and apalutamide (Erleada) after radical prostatectomy.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9321995/

5‐year follow‐up results from the STAMPEDE randomised trial ... A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone ...

5. curetoday.com curetoday.com/view/prostate-cancer-outcomes-improve-with-zytiga-prednisone-erleada

Prostate Cancer Outcomes Improve With Zytiga, ... Patients with prostate cancer showed improvements after receiving Zytiga (abiraterone acetate), prednisone and Erleada (apalutamide) with ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT02867020?term=NCT02867020&draw=1&rank=1

NCT02867020 | Study of Abiraterone Acetate Plus ADT ... Evaluation of the activity, safety and patients reported outcome of ADT plus abiraterone, abiraterone plus APALUTAMIDE (a second-generation antiandrogen) or ...

7. thelancet.com thelancet.com/article/S0140-6736(21)02437-5/fulltext

Abiraterone acetate and prednisolone with or without ... Our results suggest a clear improvement in metastasis-free and overall survival from the addition of 2 years of abiraterone to ADT in men with ...