Apalutamide + Radiation for Prostate Cancer

(BALANCE Trial)

Recruiting at 427 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

324 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well radiation therapy with or without apalutamide works in treating patients with prostate cancer that has come back (recurrent). Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgen can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may lessen the amount of androgen made by the body. Giving radiation therapy and apalutamide may work better at treating prostate cancer compared to radiation therapy alone.

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 the combination of Apalutamide and Radiation Therapy safe for treating prostate cancer?

External beam radiation therapy (EBRT) for prostate cancer can cause side effects like bowel, bladder, and sexual function issues. However, studies show that when used in certain ways, such as with dose adjustments or in combination with other treatments, it is generally well-tolerated with mostly low-grade side effects. No specific safety data for Apalutamide combined with radiation was found, but radiation therapy alone has been studied extensively. ^{1 2 3 4 5}

How is the treatment of Apalutamide + Radiation for Prostate Cancer different from other treatments?

The combination of Apalutamide (a drug that blocks male hormones) with External Beam Radiation Therapy (EBRT) is unique because it combines hormone therapy with targeted radiation, potentially enhancing the effectiveness of treatment by both reducing hormone levels that fuel cancer growth and directly targeting cancer cells with radiation. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Apalutamide + Radiation for Prostate Cancer?

Research shows that adding external beam radiotherapy (EBRT) to androgen deprivation therapy (ADT) can improve survival in men with locally advanced prostate cancer, suggesting that combining radiation with hormone therapy may be beneficial. ^{9 11 12 13 14}

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 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 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]

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 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]

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 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]

Citations

1. United States 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. [2018]

2. United States 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. [2013]

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

Long-term outcome for very high-risk prostate cancer treated primarily with a triple modality approach to include permanent interstitial brachytherapy. [2012]

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

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Estimating the Impact of Randomised Control Trial Results on Clinical Practice: Results from a Survey and Modelling Study of Androgen Deprivation Therapy plus Radiotherapy for Locally Advanced Prostate Cancer. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcomes from Dose-Reduced Radiotherapy to the Prostate in Elderly Patients with Localized Prostate Cancer. [2021]

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

Combined transperineal implant and external beam radiation for the treatment of prostate cancer: a large patient cohort in the community setting. [2012]

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

External beam radiation therapy with or without low-dose-rate brachytherapy: Analysis of favorable and unfavorable intermediate-risk prostate cancer patients. [2019]

9. Greece pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. [2022]

10. Australia 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. [2018]

11. Ireland pubmed.ncbi.nlm.nih.gov

3D conformal HDR brachytherapy and external beam irradiation combined with temporary androgen deprivation in the treatment of localized prostate cancer. [2006]

12. Germany pubmed.ncbi.nlm.nih.gov

Hypofractionated conformal HDR brachytherapy in hormone naïve men with localized prostate cancer. Is escalation to very high biologically equivalent dose beneficial in all prognostic risk groups? [2006]

13. Greece pubmed.ncbi.nlm.nih.gov

External beam radiotherapy for prostate cancer: current position and trends. [2006]

14. United States 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. [2013]