Apalutamide + Radiotherapy for Prostate Cancer

(PRIMORDIUM Trial)

Recruiting at 188 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

694 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if adding a new medication to standard prostate cancer treatments can better delay the spread of cancer or death. The combination works by blocking male hormones, killing cancer cells, and lowering hormone levels.

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.

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

Research shows that combining hormone therapy, like LHRHa, with radiation therapy improves survival rates in prostate cancer patients by reducing the chances of the cancer returning or spreading. This suggests that using Apalutamide, a similar hormone therapy, with radiotherapy could also be effective. ^{1 2 3 4 5}

Is the combination of Apalutamide and Radiotherapy safe for treating prostate cancer?

The combination of luteinizing hormone-releasing hormone (LHRH) analogs and external beam radiation therapy has been studied and found to be generally well tolerated, with low incidence of acute side effects like mild blood, intestinal, and urinary issues. Late side effects were rare, with only a few cases of rectal bleeding and chronic diarrhea reported. ^{3 6 7 8 9}

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

This treatment is unique because it combines apalutamide, a new-generation anti-androgen that blocks male hormones, with radiotherapy to potentially improve the effectiveness of radiation in treating prostate cancer, especially in patients with advanced disease. This approach is different from traditional treatments that typically use older anti-androgens like bicalutamide. ^{1 2 3 10 11}

Research Team

Janssen Pharmaceutica N.V., Belgium Clinical Trial

Principal Investigator

Janssen Pharmaceutica N.V., Belgium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Biljana Naumovic

Janssen Pharmaceutica N.V., Belgium

Chief Medical Officer since 2019

MD from Belgrade University Medical School, Executive Education from London Business School

Findings from Research

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]

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]

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]

References

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

Neoadjuvant hormone therapy for radical prostate radiotherapy: bicalutamide monotherapy vs. luteinizing hormone-releasing hormone agonist monotherapy: a single-institution matched-pair analysis. [2014]

2. France pubmed.ncbi.nlm.nih.gov

[Current studies of combined radiotherapy-hormone therapy in localized and locally advanced prostatic cancers]. [2019]

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

External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Combination of radiotherapy and hormonotherapy in locally advanced cancers of the prostate]. [2019]

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

Nonrandomized Comparison of Efficacy and Side Effects of Bicalutamide Compared With Luteinizing Hormone-Releasing Hormone (LHRH) Analogs in Combination With Radiation Therapy in the CHHiP Trial. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

[Neoadjuvant combined hormonal therapy and radiotherapy with external beam irradiation in prostatic carcinoma]. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Recovery of serum testosterone after neoadjuvant androgen deprivation therapy and radical radiotherapy in localized prostate cancer. [2022]

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

Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical and Biological Characterisation of Localised High-risk Prostate Cancer: Results of a Randomised Preoperative Study of a Luteinising Hormone-releasing Hormone Agonist with or Without Abiraterone Acetate plus Prednisone. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Apalutamide radio-sensitisation of prostate cancer. [2023]