Apalutamide + Radiation for Prostate Cancer

(BALANCE Trial)

Not currently recruiting at 441 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: NRG Oncology

Must not be taking: Seizure threshold-lowering drugs

Disqualifiers: Metastatic disease, Prior invasive malignancy, Seizure history, Uncontrolled 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

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 tests whether adding the drug apalutamide to radiation therapy is more effective than using radiation therapy alone for treating prostate cancer that has returned after surgery. Radiation uses high-energy rays to target and kill cancer cells, while apalutamide (also known as Erleada) reduces hormones that promote cancer growth. Men who had prostate surgery in the past 10 years and have experienced a recurrence, as indicated by certain PSA levels (a protein produced by prostate cells), might be suitable candidates for this trial. As a Phase 2 trial, this 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 requires that certain medications be stopped before treatment starts. Specifically, finasteride or dutasteride must be stopped before treatment begins. Additionally, any medications known to lower the seizure threshold must be discontinued or substituted at least 30 days before starting the trial.

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

Research has shown that apalutamide, the drug tested in this trial, is generally safe. In one study, only 0.2% of patients taking apalutamide died from a stroke, matching the rate of those taking a placebo—a harmless pill with no active ingredients.

Other studies have found apalutamide to be safe and effective in both real-world use and clinical trials. This indicates that while no treatment is without risk, most patients tolerate apalutamide well.

Since this trial is in Phase 2, earlier studies have already confirmed some safety aspects. The current trial focuses on evaluating the treatment's effectiveness while continuing to monitor its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining apalutamide with radiation therapy for prostate cancer because it targets the androgen receptor, a key player in prostate cancer growth, in a way that existing treatments like hormone therapy do not. Unlike standard hormone treatments that broadly lower testosterone levels, apalutamide works by directly blocking the androgen receptor, potentially reducing side effects associated with hormone therapy. This approach could enhance the effectiveness of radiation therapy, offering a more targeted attack on cancer cells and possibly improving outcomes for patients.

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

Research has shown that apalutamide, when combined with hormone therapy (ADT), treats prostate cancer by reducing hormone levels that promote cancer growth. In studies, apalutamide and ADT achieved a 65.1% survival rate at 48 months, compared to 51.8% with a placebo and ADT, significantly lowering the risk of death. Another study found that apalutamide reduced the risk of death by 23% in patients with prostate cancer that has spread but still responds to hormone therapy. In this trial, one group of participants will receive radiation therapy with apalutamide, while another group will receive radiation therapy with a placebo. These findings suggest that adding apalutamide to radiation therapy might be more effective than using radiation alone for treating recurring prostate cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Felix Y Feng

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

Men with stage III-IV prostate cancer who've had a prostatectomy within the last 10 years, have certain PSA levels, and meet specific health criteria can join. They must not have had prior chemotherapy for prostate cancer or radiotherapy overlapping the treatment area, among other exclusions.

Inclusion Criteria

My cancer is at least stage T3a.

I can care for myself and am able to carry on normal activities.

My surgical sample is available for genomic analysis or I already have the results for validation.

Exclusion Criteria

For patients who have not undergone prior Decipher analysis, submission of the specimen to GenomeDx should be as soon as possible after study registration (Step 1) as these results can take up 21 days after the specimen is received at GenomeDx; Step 2 registration must occur within 6 weeks (42 days) of Step 1 registration; if Decipher results have already been obtained, in lieu of tissue, results must be submitted to GenomeDx for validation

Patients must not plan to participate in any other clinical trials while receiving treatment on this study or being followed post-protocol therapy.

I have had seizures or conditions that increase my risk of seizures, like a stroke within the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo external beam radiation therapy for 7-8 weeks

7-8 weeks

Weekly visits for radiation therapy

Treatment

Patients receive either placebo or apalutamide orally once daily for up to 6 cycles

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide
• External Beam Radiation Therapy

Trial Overview The trial is testing if adding apalutamide to radiation therapy improves outcomes in treating prostate cancer compared to radiation alone. Apalutamide blocks androgens which may fuel cancer growth.

How Is the Trial Designed?

Group I: Arm 2 (radiation therapy, apalutamide) Experimental Treatment 2 Interventions

Patients undergo external beam radiation therapy on day 1 for 7-8 weeks. Beginning on day of radiation therapy, patients receive apalutamide PO QD on days 1-30. Treatment repeats every 30 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm 1 (radiation therapy, placebo) Active Control 2 Interventions

Patients undergo external beam radiation therapy on day 1 for 7-8 weeks. Beginning on day of radiation therapy, patients receive placebo PO QD on days 1-30. Treatment repeats every 30 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

External Beam Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in United States as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Canada as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Japan as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in China as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Approved in Switzerland as External Beam Radiation Therapy for:

• Various types of cancer, including but not limited to breast, lung, prostate, and brain cancers

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 215 patients with locally advanced prostate cancer, 97.5% of those treated with external beam radiation therapy (EBRT) showed no biochemical failure after a mean follow-up of 17.3 months, indicating high efficacy of the treatment protocol.

The study suggests that intermittent androgen ablation therapy after EBRT may be a viable option, although the follow-up period was short and further research is needed to confirm long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer. Yamanaka, H., Ito, K., Naito, S., et al.[2013]

External beam radiotherapy (EBRT) for loco-regional prostate cancer shows comparable 10-year survival rates to radical prostatectomy, with survival rates of 90-95% for T1, 60-70% for T2, and 50-60% for T3 stages, indicating its effectiveness as a treatment option.

Advancements in radiotherapy techniques, such as 3D-conformal RT and intensity-modulated RT (IMRT), allow for higher radiation doses to be delivered to the tumor while minimizing damage to surrounding tissues, and the use of cytoprotection with amifostine may help reduce radiation side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiotherapy for prostate cancer: current position and trends. Koukourakis, MI., Touloupidis, S.[2006]

In a study of 173 patients with high-risk localized prostate cancer, long-term androgen deprivation therapy (ADT) for 36 months or more combined with external-beam radiotherapy (EBRT) significantly improved five-year progression-free survival rates (92.8%) compared to short-term ADT (72.9%).

Patients receiving short-term ADT experienced a higher incidence of cardiovascular toxicity (grade II or above) compared to those on long-term ADT, indicating that longer ADT may not only enhance survival but also have a more favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. Okubo, M., Nakayama, H., Itonaga, T., et al.[2022]

A study of 1,825 men with prostate cancer treated with external beam radiation therapy (EBRT) found that location of treatment significantly influenced the level of adverse effects, with one regional cancer service reporting a higher 'big bother' rate (11.1%) compared to the rest of Victoria (4.8%).

The study indicates that while the technique of EBRT did not show a significant impact on patient outcomes over time, the variation in patient-reported adverse effects highlights the importance of monitoring and evaluating treatment locations for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of patient-reported quality of life outcomes after external beam radiation treatment for prostate cancer in Victoria: A cohort study by the Victorian Prostate Cancer Registry. Patabendi Bandarage, VR., Billah, B., Millar, JL., et al.[2018]

In a study of 46,325 men with high-risk prostate cancer, androgen deprivation therapy (ADT) improved overall survival for those receiving external beam radiation therapy (EBRT) alone, but not for those receiving combined EBRT and brachytherapy.

The findings suggest that while ADT is beneficial with EBRT, it may not enhance survival in patients treated with both EBRT and brachytherapy, highlighting the need for further research to evaluate the risks and benefits of ADT in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy. Yang, DD., Muralidhar, V., Mahal, BA., et al.[2018]

In a study of 585 high-risk prostate cancer patients treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT), a biopsy Gleason score (bGS) of 8 to 10 was identified as the strongest predictor of biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM).

The study found that the duration of ADT did not significantly impact patient outcomes, highlighting the importance of tumor characteristics over treatment length in predicting survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Tendulkar, RD., Reddy, CA., Stephans, KL., et al.[2020]

In a study of 247 patients with higher risk prostate cancer, two different external beam radiotherapy (EBRT) regimens (20 Gy vs. 44 Gy) showed equivalent outcomes in biochemical progression-free survival (bPFS), cause-specific survival, and overall survival after a median follow-up of 9 years.

The findings suggest that the higher dose of EBRT does not provide additional benefits over the lower dose, likely due to the effectiveness of the high-quality brachytherapy used in conjunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

20 Gy versus 44 Gy of supplemental external beam radiotherapy with palladium-103 for patients with greater risk disease: results of a prospective randomized trial. Merrick, GS., Wallner, KE., Butler, WM., et al.[2013]

Citations

1. jnj.com jnj.com/media-center/press-releases/erleada-apalutamide-demonstrates-statistically-significant-and-clinically-meaningful-improvement-in-overall-survival-compared-to-enzalutamide-in-patients-with-metastatic-castration-sensitive-prostate-cancer

ERLEADA® (apalutamide) demonstrates statistically ... Largest head-to-head real-world study in mCSPC demonstrated that ERLEADA® reduced risk of death by 23 percent at 24 months compared to ...

2. erleadahcp.com erleadahcp.com/efficacy/

Efficacy | ERLEADA® (apalutamide) HCP Median follow-up time was 44.0 months. 1. The survival rate at 48 months was 65.1% for ERLEADA ® + ADT patients vs 51.8% for placebo + ADT patients.

3. nature.com nature.com/articles/s41391-024-00929-6

Survival outcomes of apalutamide as a starting treatment Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51– ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39893578/

Real-world clinical usage and efficacy of apalutamide in ... The secondary outcomes were the efficacy of apalutamide: PSA response (50% or 90% decline), progression-free survival, and skin-adverse events ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124002530

Apalutamide in Metastatic Castration-sensitive Prostate ... Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

6. erleadahcp.com erleadahcp.com/patient-reported-outcomes/

PATIENT-REPORTED OUTCOMES FOR HRQoL 1-6 Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA® and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39613567/

Results from the Multicenter Real-world ARON-3 Study Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1903307

Apalutamide for Metastatic, Castration-Sensitive Prostate ... In our trial, initial therapy with apalutamide in patients with metastatic, castration-sensitive prostate cancer led to improved clinical outcomes. The intent ...