Anti-Testosterone Drugs + Radiation Therapy for Prostate Cancer

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

64 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine whether anti-testosterone medications, when administered before, during, and after high-dose, precision radiation, will be effective in preventing the prostate cancer from returning.

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.

What data supports the effectiveness of the drug Abiraterone in treating prostate cancer?

Research shows that Abiraterone, when used with prednisone, significantly improves survival and delays disease progression in patients with metastatic castration-resistant prostate cancer, especially after chemotherapy. ^{1 2 3 4 5}

Is the combination of anti-testosterone drugs and radiation therapy generally safe for humans?

Abiraterone, an anti-testosterone drug, has been used in treating prostate cancer and is generally considered safe, but it can cause side effects like swelling, high blood pressure, low potassium levels, liver issues, and heart problems. Patients taking abiraterone need regular monitoring to manage these risks. ^{1 4 6 7 8}

What makes the Anti-Testosterone Drugs + Radiation Therapy treatment unique for prostate cancer?

This treatment combines anti-testosterone drugs like Abiraterone and ARN-509 with radiation therapy, offering a novel approach by targeting androgen (male hormone) production and signaling, which is crucial in prostate cancer progression. Unlike traditional treatments, this combination aims to enhance the effectiveness of radiation therapy while potentially reducing side effects associated with hormone therapy alone. ^{1 3 9 10 11}

Research Team

Sean McBride, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 Business School

John (Jack) Lawrence

Janssen Pharmaceuticals

Chief Medical Officer since 2023

MD from University of Virginia School of Medicine

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Sweden 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. [2017]

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

The role of abiraterone in the management of metastatic castration-resistant prostate cancer. [2015]

4. Germany 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. [2022]

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

Leuprolide acetate given by a subcutaneous extended-release injection: less of a pain? [2013]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020]

7. United States 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. [2018]

8. France pubmed.ncbi.nlm.nih.gov

Abiraterone. After prostate cancer treatment failure: 4-month survival advantage. [2015]

9. Netherlands pubmed.ncbi.nlm.nih.gov

[Drug treatment of prostatic carcinoma]. [2006]

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

Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02. [2022]

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

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