Radiotherapy + Enzalutamide for Recurrent Prostate Cancer

(STEEL Trial)

Recruiting at 107 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

188 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with post-prostatectomy PSA (Prostate Specific Antigen) recurrences with aggressive disease features will receive salvage radiation therapy and standard androgen deprivation therapy (ADT) or enhanced ADT to determine if there is any improvement in progression-free survival when enhanced ADT is used compared to standard ADT.

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.

What data supports the effectiveness of the treatment Radiotherapy + Enzalutamide for Recurrent Prostate Cancer?

Research shows that combining enzalutamide, a drug that blocks male hormones, with salvage radiation therapy can help control prostate cancer that returns after surgery by delaying the rise of PSA levels, which are markers of cancer activity. ^{1 2 3 4 5}

Is the combination of radiotherapy and enzalutamide safe for treating recurrent prostate cancer?

Enzalutamide, used with radiotherapy, has been studied for safety in treating prostate cancer. It is generally considered to have a favorable side effect profile, but some patients may experience side effects like severe thrombocytopenia (low platelet count) and seizures. ^{1 3 6 7 8}

How is the treatment of radiotherapy combined with enzalutamide unique for recurrent prostate cancer?

This treatment is unique because it combines salvage radiotherapy (a second chance for cure after surgery) with enzalutamide, a potent anti-androgen drug that blocks male hormones, without using additional hormone therapy. This combination aims to improve control of prostate cancer with potentially fewer side effects compared to traditional hormone therapies. ^{1 2 3 5 9}

Research Team

Hiram Gay, MD

Principal Investigator

RTOG Foundation

Edwin Posadas, MD

Principal Investigator

RTOG Foundation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

References

1. England 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). [2021]

2. England pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for the treatment of oligoprogression on androgen receptor targeted therapy in castration-resistant prostate cancer. [2020]

3. United States 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. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of salvage radiotherapy combined with endocrine therapy in patients with biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis of randomized controlled trials. [2023]

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

Salvage surgery or salvage radiotherapy for locally recurrent prostate cancer. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Enzalutamide-induced severe thrombocytopenia complicated by a seizure in a 76-year-old man with castration-resistant prostate cancer. [2022]

7. Switzerland 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. [2023]

8. England 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. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Salvage reirradiation for locoregional failure after radiation therapy for prostate cancer: who, when, where and how? [2022]