Radiotherapy + Enzalutamide for Recurrent Prostate Cancer

(STEEL Trial)

Not currently recruiting at 110 trial locations

Overseen By Edwin Posadas, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: RTOG Foundation, Inc.

Must be taking: GnRH analogs

Must not be taking: HAART

Disqualifiers: Metastatic disease, Chemotherapy, IBD, 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 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether adding enzalutamide, a type of hormone therapy, to standard prostate cancer treatment can prevent disease progression in men whose cancer has returned after surgery. It compares standard hormone therapy with this enhanced approach to determine if it improves outcomes. The trial targets men who underwent prostate cancer surgery in the past 10 years, are experiencing rising PSA levels (a marker of prostate cancer), and show signs of aggressive cancer features, such as a high Gleason score or other specific criteria. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on HIV treatment with HAART, you may not be eligible to participate.

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

Previous studies have shown that enzalutamide is generally safe. Patients with prostate cancer who took enzalutamide lived for an average of 37 months without cancer spreading, compared to 15 months for those on a placebo. This suggests that enzalutamide not only delays cancer progression but is also generally safe.

Enzalutamide is usually well-tolerated, though it can have side effects. Common side effects include fatigue, hot flashes, and high blood pressure, which were mostly mild to moderate.

Radiation therapy, a standard treatment for prostate cancer, is generally considered safe. Some individuals might experience temporary skin irritation, fatigue, or bladder issues during or after treatment.

Overall, the combination of treatments in this trial appears safe based on prior studies. However, discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for recurrent prostate cancer because they explore the potential of combining radiotherapy with enhanced androgen deprivation therapy (ADT) using enzalutamide. Unlike traditional ADT, which often involves a GnRH analog and sometimes bicalutamide, this approach includes enzalutamide, which blocks testosterone more effectively. This combination aims to improve outcomes by intensifying the hormonal blockade, potentially slowing cancer progression more effectively than standard treatments. This innovative strategy could offer new hope for patients whose cancer has returned after initial treatment.

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

Research has shown that enzalutamide, one of the treatments in this trial, can extend the lives of men with prostate cancer when combined with other hormone treatments. One study found that combining enzalutamide with GnRH therapy led to fewer cases of cancer progression compared to a placebo. Another study reported that about 87% of patients who took enzalutamide with leuprolide (a hormone treatment) remained alive without cancer worsening. This trial will compare the effectiveness of Salvage Radiation Therapy with Enhanced ADT, which includes enzalutamide, against Salvage Radiation Therapy with Standard ADT. These findings support the use of enhanced hormone therapy with enzalutamide to potentially improve outcomes for prostate cancer patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Edwin Posadas, MD

Principal Investigator

RTOG Foundation

Hiram Gay, MD

Principal Investigator

RTOG Foundation

Are You a Good Fit for This Trial?

Men with recurrent prostate cancer after surgery, having a high Gleason score (8-10), elevated PSA levels, and certain aggressive disease features are eligible. They must have adequate blood counts and organ function. Exclusions include heart failure, metastatic disease, prior chemotherapy for prostate cancer, seizures or conditions predisposing to them, uncontrolled hypertension or infections, recent cardiovascular events or falls.

Inclusion Criteria

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN within 90 days prior to registration

My PSA level is at least 0.2 ng/mL, or 0.1 ng/mL with an ultrasensitive test.

My prostate cancer has spread to the seminal vesicles.

Exclusion Criteria

I have a history of seizures or conditions that could lead to seizures.

You have a history of falling and breaking bones multiple times in the past year, and the doctor thinks that taking certain medications could make your bones weaker.

I've had radiation in the same area as my current cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive salvage radiation therapy and androgen deprivation therapy (ADT) for prostate cancer recurrence

24 months

Regular visits as per treatment protocol

Radiation

Salvage radiation therapy (SRT) administered over 7-8 weeks

7-8 weeks

Daily visits for radiation sessions

Follow-up

Participants are monitored for progression-free survival and other outcomes

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Bicalutamide
• Enzalutamide
• Salvage Radiotherapy

Trial Overview The trial is testing whether adding the drug Enzalutamide to salvage radiation therapy and standard hormone therapy improves progression-free survival in men whose prostate cancer has returned post-surgery compared to just radiation and standard hormone therapy alone.

How Is the Trial Designed?

Group I: Salvage Radiation Therapy + Enhanced ADT Experimental Treatment 3 Interventions

Enhanced ADT: 24 months of GnRH analog (any formulation) with 24 months of enzalutamide (160 mg/day). SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.

Group II: Salvage Radiation Therapy (SRT) + Standard androgen deprivation therapy (ADT) Active Control 3 Interventions

Standard ADT: 24 months of GnRH analog (any formulation) with optional 1-4 months of bicalutamide (50 mg/day). SRT: Starting within 0-70 days of initiation of GnRH analog, 66.6-70.2 Gy as 1.8 Gy/fraction in 37-39 fractions or 66.0-70.0 Gy as 2.0 Gy/fraction in 33-35 fractions lasting approximately 7-8 weeks, and optional lymph node boost.

Who Is Running the Clinical Trial?

RTOG Foundation, Inc.

Lead Sponsor

Trials

7

Recruited

1,500+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Published Research Related to This Trial

Enzalutamide demonstrated significant efficacy in managing non-metastatic castration-resistant prostate cancer, with a median prostate-specific antigen-progression-free survival of 35.0 months in a study of 66 Japanese patients.

The treatment showed a high prostate-specific antigen response rate of 88.9%, with most patients experiencing manageable adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide in patients with non-metastatic castration-resistant prostate cancer after combined androgen blockade for recurrence following radical treatment in Japan (Japanese research for patients with non-metastatic castration-resistant prostate cancer-enzalutamide: JCASTRE-zero)-a prospective single-arm interventional study. Sugimoto, M., Kato, T., Tohi, Y., et al.[2022]

The SALV-ENZA trial is a phase II study involving adult males with recurrent prostate cancer after surgery, testing the effectiveness of combining salvage radiation therapy (SRT) with the anti-androgen enzalutamide to improve outcomes like freedom from PSA progression.

This study aims to determine if adding enzalutamide, known for its favorable side effect profile, enhances the efficacy of SRT compared to standard treatment alone, potentially leading to better clinical outcomes and paving the way for future phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II randomized placebo-controlled double-blind study of salvage radiation therapy plus placebo versus SRT plus enzalutamide with high-risk PSA-recurrent prostate cancer after radical prostatectomy (SALV-ENZA). Kapoor, R., Deek, MP., McIntyre, R., et al.[2021]

In a study of 86 men with recurrent prostate cancer, combining enzalutamide (ENZA) with salvage radiation therapy (SRT) significantly improved freedom from prostate-specific antigen (PSA) progression, with a 2-year FFPP of 84% for ENZA compared to 66% for placebo.

The treatment was found to be safe, with common side effects including fatigue and urinary frequency, but the long-term effects on distant metastasis or overall survival are still unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Randomized Study of Salvage Radiation Therapy Plus Enzalutamide or Placebo for High-Risk Prostate-Specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy: The SALV-ENZA Trial. Tran, PT., Lowe, K., Tsai, HL., et al.[2023]

A 76-year-old man developed severe thrombocytopenia after 13 days of enzalutamide treatment for castration-resistant prostate cancer, indicating that this side effect can occur early in therapy.

After discontinuing enzalutamide, the patient's platelet count recovered, and he was able to restart the medication without recurrence of thrombocytopenia; however, he later experienced a seizure, suggesting that enzalutamide may also be associated with neurological adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. Murata, M., Takizawa, I., Maruyama, R., et al.[2022]

A case study of a patient with castration-resistant prostate cancer showed that combining ablative stereotactic body radiation therapy with ongoing enzalutamide treatment resulted in a durable complete remission, despite prior progression on the medication.

This finding highlights the potential for innovative treatment strategies in advanced prostate cancer and suggests the need for further clinical trials to explore this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer. Nguyen, TC., Bajwa, R., Bari, S., et al.[2020]

In a study of 554 prostate cancer patients who received salvage radiotherapy (SRT) after surgery, escalating the radiation dose to 7000 cGy or more significantly improved progression-free survival compared to lower doses, with a median follow-up of 6.8 years.

Factors such as lower tumor stages and lower Gleason scores were also associated with better progression-free survival, but the study found no significant impact on overall survival, indicating the need for longer follow-up to fully understand the benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Dose Escalation on the Efficacy of Salvage Radiotherapy for Recurrent Prostate Cancer-A Risk-Adjusted, Matched-Pair Analysis. Böhmer, D., Siegmann, A., Scharl, S., et al.[2023]

Citations

1. xtandihcp.com xtandihcp.com/cspc/efficacy

Efficacy CSPC | HCP Site | XTANDI® (enzalutamide) Number of events: 45 (12.7%) with XTANDI + GnRH therapy* vs 92 (25.7%) with placebo + GnRH therapy* · Median metastasis-free survival was not reached in either ...

2. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-significantly-improves-survival

XTANDI® Plus Leuprolide Significantly Improves Survival ... XTANDI® Plus Leuprolide Significantly Improves Survival Outcomes in Men with Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12504157/

Comparative effectiveness and safety of enzalutamide ... This large-scale, real-world study demonstrates that enzalutamide is associated with improved overall survival and a lower risk of treatment ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMx250003

Improved Outcomes with Enzalutamide in Biochemically ... Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. VIEW THE RELATED ARTICLE. Published August 1, 2025. N Engl J Med 2025;393:832.

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/fda-xtandi-prostate-cancer-psa-recurrence

Xtandi Approved for High-Risk Prostate Cancer - NCI Freedland and his colleagues reported, about 87% of participants treated with enzalutamide and leuprolide were still alive with no evidence of ...

6. xtandihcp.com xtandihcp.com/cspc/safety

Safety Profile in CSPC Learn about the efficacy and safety of XTANDI® (enzalutamide) in the results of the AFFIRM Trial for post-docetaxel mCRPC patients. See Risk Info.

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303974

Improved Outcomes with Enzalutamide in Biochemically ... Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of ...

8. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/xtandi

Xtandi | European Medicines Agency (EMA) Patients treated with Xtandi lived for an average of 37 months without their disease becoming metastatic compared with 15 months on placebo.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12114795/

Safety and Efficacy of Reduced Dose of Enzalutamide in ... Recent EMBARK findings highlight Enzalutamide's potential in high-risk localized prostate cancer, showing significant improvements in metastasis ...

10. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-reduced-risk-death-40-vs-leuprolide

XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ... The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...