Apalutamide + Radiotherapy for Prostate Cancer

(PRIMORDIUM Trial)

Not currently recruiting at 240 trial locations

Overseen By Study Contact

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Janssen Pharmaceutica N.V., Belgium

Must be taking: LHRH agonists

Must not be taking: CYP17 inhibitors, AR antagonists

Disqualifiers: Pelvic radiation, ADT, chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding the drug apalutamide to standard prostate cancer treatment can delay disease spread or improve survival. It targets men who have undergone prostate surgery and still show signs of cancer, specifically those with rising PSA levels (a protein indicating prostate activity) after surgery. Participants will receive either standard treatment with radiotherapy (also known as radiation therapy or X-ray therapy) and hormone therapy (LHRHa), or the same treatment plus apalutamide. This trial may suit those who have had prostate cancer surgery, are experiencing rising PSA levels, and have not previously received radiation or hormone therapy for this condition. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in prostate cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain medications like androgen receptor antagonists or CYP17 inhibitors, you may not be eligible to participate.

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

Research has shown that apalutamide, the medication tested with radiotherapy, has been generally safe in earlier trials. Real-world studies have confirmed that apalutamide is safe and effective for patients with prostate cancer. In some studies, a very small number of patients, about 0.2%, experienced serious issues like problems with blood flow in the brain, but these were rare.

Radiotherapy has long been a common treatment for prostate cancer. It is known to be effective, and most patients tolerate it well. Common side effects might include tiredness and skin irritation, but these are usually manageable.

Overall, both apalutamide and radiotherapy have been well-tolerated in past studies, providing reassurance about their safety in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about the combination of apalutamide with radiotherapy for prostate cancer because it introduces a potentially powerful synergy. Unlike the standard of care, which often includes treatments like surgery, radiation, and hormone therapy alone, this approach combines radiotherapy with apalutamide, an advanced androgen receptor inhibitor. Apalutamide works by blocking the effects of male hormones that can fuel cancer growth, and when paired with radiotherapy, it might enhance the effectiveness of cancer cell eradication. Additionally, the study is exploring different combinations with or without the drug to understand its added benefits, aiming to improve outcomes for patients by offering a more comprehensive attack on the cancer.

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

In this trial, one group of participants will receive apalutamide combined with radiotherapy and hormone therapy (LHRHa). Studies have shown that apalutamide can significantly improve survival rates in prostate cancer patients. Specifically, one study found that 65.1% of patients taking apalutamide with hormone therapy (ADT) were alive after 48 months, compared to 51.8% of those taking a placebo with ADT. Research indicates that apalutamide can reduce the risk of death by 23% over two years in men with prostate cancer that has spread but still responds to hormone therapy. Both real-world use and clinical trials have deemed it safe. Adding apalutamide to radiation treatment may help delay cancer spread, as it effectively slows prostate cancer progression. ^{2 5 6 7 8}

Who Is on the Research Team?

Janssen Pharmaceutica N.V., Belgium Clinical Trial

Principal Investigator

Janssen Pharmaceutica N.V., Belgium

Are You a Good Fit for This Trial?

Men with high-risk, hormone-sensitive prostate cancer who've had a prostatectomy and show no signs of metastasis. They must have a PSA <0.1 ng/mL post-surgery, good performance status (able to carry out daily activities), and be at high risk for metastasis based on specific criteria like Gleason score or PSADT. Participants need to swallow pills and undergo PSMA-PET scans.

Inclusion Criteria

I can swallow pills whole or mix them with apple sauce.

I had prostate surgery and my PSA was below 0.1 ng/mL between 6 and 20 weeks after.

My scans show no signs of prostate cancer spread, except possibly one bone lesion.

Exclusion Criteria

I have been treated with hormone therapy for prostate cancer.

I have had radiation treatment for cancer in my pelvic area.

I am allergic or react badly to apalutamide, LHRH agonists, or their ingredients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive radiotherapy and LHRH agonist, with or without apalutamide, for prostate cancer treatment

26 weeks

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 9 years

Biannual visits for observational cohort

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide
• LHRHa
• Radiotherapy

Trial Overview The trial is testing if adding Apalutamide to standard treatment with Radiotherapy plus LHRH agonist can delay the spread of cancer or death in men with high-risk prostate cancer. The effectiveness will be measured using advanced imaging techniques like PSMA-PET.

How Is the Trial Designed?

Group I: Interventional Cohort (Group 2): RT+LHRHa + Apalutamide Experimental Treatment 3 Interventions

Participants will receive prostate-bed plus pelvic lymph node salvage external-beam radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), along with a LHRHa as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization. Participants will also receive 240 milligram (mg) of apalutamide starting within 3 days after randomization as film-coated tablets, to be swallowed whole and together once daily with or without food, for a period of 180 Days.

Group II: Interventional Cohort (Group 1): RT+ LHRHa Active Control 2 Interventions

Participants will receive radiotherapy (RT) which is defined as prostate-bed plus pelvic lymph node salvage external-beam radiotherapy with or without optional stereotactic body radiation therapy (SBRT), along with a luteinizing hormone-releasing hormone agonist (LHRHa) as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization.

Group III: Observational Cohort(Group3) PSMA-PET Negative Participants Active Control 1 Intervention

Enrollment into this cohort will be stopped further. Participants who were PSMA-PET-negative at screening and were already enrolled in the Observational Cohort will continue in this cohort. Data collected in the course of routine clinical practice during this period will include clinical evaluations, disease progression, therapies administered as per standard-of-care at the study-sites and survival status. For Observational Cohort, information will be entered into the electronic case report form (eCRF) from the medical records at least twice a year. The use of any medicinal product(s) for the treatment and management of participants will be at discretion of the treating physician.

Who Is Running the Clinical Trial?

Janssen Pharmaceutica N.V., Belgium

Lead Sponsor

Trials

84

Recruited

31,600+

Joaquin Duato

Janssen Pharmaceutica N.V., Belgium

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Pharmaceutica N.V., Belgium

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

In three clinical trials for locally advanced prostate cancer, combining external irradiation with LHRH analogues significantly improved various survival rates, including disease-free and overall survival, with a notable P-value of < 0.001.

The EORTC trial 22863 specifically demonstrated a significant overall survival benefit when using the LHRH analogue goserelin acetate from the start of irradiation for three years, while the RTOG trial 85-31 showed survival improvements in patients with poorly differentiated tumors when the LHRH analogue was started during the last week of irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current studies of combined radiotherapy-hormone therapy in localized and locally advanced prostatic cancers]. Bolla, M., Artignan, X., Chirpaz, E., et al.[2019]

Apalutamide demonstrated stronger radio-sensitizing effects compared to bicalutamide in both hormone-sensitive and hormone-resistant prostate cancer cell lines, suggesting it may enhance the effectiveness of radiotherapy.

In vivo studies showed that combining apalutamide with radiotherapy resulted in significantly greater tumor necrosis in mouse models, indicating a potential for improved treatment outcomes in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide radio-sensitisation of prostate cancer. Kakouratos, C., Kalamida, D., Lamprou, I., et al.[2023]

The SAVE trial is a Phase II study involving 202 men with advanced prostate cancer, comparing the effects of apalutamide combined with salvage radiotherapy against androgen-deprivation therapy plus salvage radiotherapy.

The primary goal is to evaluate sexual function after nine months of treatment, while also assessing quality of life, safety, and short-term efficacy of apalutamide, highlighting its potential benefits in managing prostate cancer post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. Dirix, P., Strijbos, M., den Mooter, TV., et al.[2021]

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 ...