Anti-Testosterone Drugs + Radiation Therapy for Prostate Cancer

Not currently recruiting at 10 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Anti-testosterone

Must not be taking: Steroidal antiandrogens, Non-steroidal antiandrogens, CYP3A4 inducers, Seizure threshold reducers

Disqualifiers: Metastatic disease, Prior prostate treatment, Severe hepatic impairment, 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: 4

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if anti-testosterone drugs, combined with precision radiation therapy, can prevent the recurrence of prostate cancer. Participants will take medications such as abiraterone (Zytiga or Yonsa), ARN-509, and leuprolide (Lupron, Eligard, or Viadur) before, during, and after receiving targeted radiation. The trial seeks men with prostate cancer who have specific high-risk features, like a high Gleason score or elevated PSA levels, but without any signs of cancer spreading to other parts of the body. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. Specifically, you cannot have used steroidal antiandrogens, AR partial agonists, ketoconazole, chemotherapy, immunotherapy, estrogens, or radiopharmaceuticals within 3 months before joining. Additionally, non-steroidal anti-androgens must not have been used within 1 month before joining, and medications that lower the seizure threshold must be stopped 4 weeks before joining.

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

Research shows that the treatments in this trial are generally safe.

For Abiraterone, studies indicate it does not pose a higher risk of serious side effects compared to standard treatments. However, almost all patients experience some side effects, which are usually manageable. A key concern is potential liver issues, so regular monitoring is important during treatment.

ARN-509, also known as Apalutamide, is considered safe and well-tolerated. Most patients continue treatment without major issues, and it has been effective in controlling cancer.

Leuprolide has a well-known safety record. It is generally well-tolerated, with some patients experiencing temporary pain at the injection site. There is a slightly higher risk of heart-related issues compared to some other treatments, but it is still commonly used.

Studies have found stereotactic ultra-fractionated radiotherapy to be well-tolerated, with only minor side effects. Most patients report good survival rates with this precise form of radiation.

In summary, each treatment has a strong safety record according to studies, but monitoring for side effects is important with any treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine anti-testosterone drugs like Abiraterone, ARN-509, and Leuprolide with advanced radiation therapy techniques for prostate cancer. This combination targets the cancer more aggressively by both blocking testosterone, which fuels prostate cancer growth, and delivering precise radiation to cancer cells. Unlike traditional options that might use either hormonal therapy or radiation alone, this approach maximizes the chances of attacking the cancer from multiple angles. This strategy has the potential to be more effective in shrinking tumors and slowing disease progression, offering hope for improved outcomes in patients.

What evidence suggests that these treatments might be effective for prostate cancer?

Research shows that the combination of treatments tested in this trial has effectively treated prostate cancer. Participants will receive Abiraterone, which helps patients live longer and slows cancer growth, and ARN-509, also known as apalutamide, which lowers prostate-specific antigen (PSA) levels, a marker for tracking prostate cancer. Leuprolide, another component, significantly reduces testosterone levels, slowing cancer growth. Lastly, stereotactic ultra-fractionated radiotherapy effectively controls prostate cancer with minimal side effects. Together, these treatments target different aspects of prostate cancer, showing promise in preventing its return. ^{1 2 3 5 6}

Who Is on the Research Team?

Sean McBride, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer, not previously treated for it, can join this trial. They need a PSA level ≥20 ng/mL and clinical stage ≥T3 disease. Key organ functions must be normal, including liver and kidney tests. Participants should have no active infections like HIV or hepatitis that would make steroid use risky, no recent other cancer treatments or surgeries, and agree to use contraception during the study.

Inclusion Criteria

Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information

PSA ≥20 ng/mL within two months prior to registration

IPSS (International Prostate Symptom Score) ≤ 20F

Exclusion Criteria

I have a specific type of inflammatory bowel disease.

I have a specific condition affecting my digestive system.

I have active symptoms of viral hepatitis or chronic liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive leuprolide, abiraterone, and ARN-509 for a total of 6 months, starting 3 months prior to radiation therapy and continuing until approximately 3 months post-radiation therapy.

6 months

Visits every 4 weeks (±1 week) and at least once during radiation therapy

Radiation

Participants undergo high-dose, precision radiation therapy.

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on biochemical failure as indicated by PSA levels.

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• ARN-509
• Leuprolide
• Stereotactic, Ultra-fractionated Radiotherapy

Trial Overview The trial is testing if anti-testosterone drugs (Abiraterone and ARN-509) combined with Leuprolide and high-dose precision radiotherapy can prevent prostate cancer from returning. Patients will receive these medications before, during, and after the radiation treatment to see how effective they are together.

How Is the Trial Designed?

Group I: patients with prostate cancer Experimental Treatment 4 Interventions

Eligible patients will receive a total of 6 months of leuprolide, abiraterone, and ARN-509 to begin three months prior to RT and continuing until approximately 3 months post-RT. Patients will be assessed every 4 weeks (±1 week) (a cycle = 28 days) throughout their treatment with the study drugs, and at least once during RT.

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

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

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

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

Abiraterone acetate (Zytiga®) is an effective antiandrogen for prostate cancer but has poor oral bioavailability (<10%) and requires patients to fast around its administration due to a significant food effect (5-10-fold increase in absorption).

The review highlights the need for improved oral formulation strategies to enhance solubility and bioavailability of abiraterone acetate, aiming to reduce the required dose and eliminate the food effect, which could lead to better patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. Schultz, HB., Meola, TR., Thomas, N., et al.[2020]

Oral abiraterone acetate (Zytiga®) effectively inhibits androgen biosynthesis, which is crucial for the progression of metastatic castration-resistant prostate cancer (mCRPC), and has been shown to prolong overall survival and radiographic progression-free survival in large phase 3 trials.

In combination with prednisone, abiraterone acetate has a manageable safety profile and is a convenient once-daily treatment option, making it a significant first-line therapy for men with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer. Scott, LJ.[2019]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5543693/

Safety and Antitumor Activity of Apalutamide (ARN-509) in ... Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC with 80% of AAP-naïve and 43% of post-AAP patients remaining on treatment for ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27160947/

Phase 2 Study of the Safety and Antitumor Activity of ... - PubMed Overall, 89% of patients had ≥50% PSA decline at 12 wk. Median TTPP was 24.0 mo (95% confidence interval [CI], 16.3 mo-not reached [NR]); median MFS was NR (95% ...

3. aacrjournals.org aacrjournals.org/cancerres/article/72/6/1494/577561/ARN-509-A-Novel-Antiandrogen-for-Prostate-Cancer

ARN-509: A Novel Antiandrogen for Prostate Cancer Treatment These data support clinical development of ARN-509 for treatment of castration-sensitive and -resistant prostate cancer.

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2012.30.5_suppl.43

Phase I/II safety and pharmacokinetic (PK) study of ARN- ... Conclusions: In this Phase 1 study, ARN-509 was shown to be safe and well tolerated, with promising preliminary activity based on PSA and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0302283816301336

Phase 2 Study of the Safety and Antitumor Activity ... On the basis of these promising preclinical results, a first-in-human phase 1/2 study was conducted (ARN-509-001) in patients with CRPC.

6. aacrjournals.org aacrjournals.org/clincancerres/article/23/14/3544/122974/Safety-and-Antitumor-Activity-of-Apalutamide-ARN

Safety and Antitumor Activity of Apalutamide (ARN-509) in ... Primary endpoint was ≥50% decline in 12-week PSA according to Prostate Cancer Working Group 2 criteria. Secondary endpoints included time to PSA progression and ...