Apalutamide + Targeted Radiation for Prostate Cancer

Recruiting at 324 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: Androgen deprivation

Disqualifiers: Seizures, Inflammatory bowel disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 6 months

804 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for prostate cancer in men with rising PSA levels (a protein made by prostate cells) after surgery. It tests whether adding the drug apalutamide (Erleada), sometimes with other medications and targeted radiation therapy, to standard treatments like prostate radiation and hormone therapy can better control cancer. The trial targets those who have had prostate surgery and now face a biochemical recurrence, with some showing signs of cancer spreading outside the pelvis. Participants should have undergone prostate surgery and noticed a PSA rise, but not have cancer spread beyond the pelvis according to standard imaging tests. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that a short course of low-dose anti-androgen like bicalutamide is allowed before starting the study treatment. It's best to discuss your current medications with the trial team.

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

Research has shown that apalutamide, the main treatment in this trial, is generally safe and well-tolerated for treating prostate cancer. One study found that about 20% of patients taking apalutamide with other prostate cancer treatments experienced serious side effects, similar to the rate in those taking a placebo. Most patients continued the treatment over time, indicating its manageability.

Targeted radiation therapy is also considered a safe and effective option for prostate cancer, particularly for cancers that have spread beyond the prostate. This type of radiation minimizes harm to healthy tissue while focusing on cancer cells and is known to be well-tolerated.

Both treatments have a history of being manageable for patients, which is important for those considering joining a trial. Consulting with a healthcare provider is essential to determine if these treatments are suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about apalutamide combined with targeted radiation for prostate cancer because it offers a novel approach to managing the disease. Unlike standard treatments, which often rely heavily on hormone therapy alone, this approach integrates apalutamide, an androgen receptor inhibitor, with advanced radiation techniques. This combination aims to more precisely target cancer cells while potentially reducing side effects associated with conventional hormone therapies. By enhancing the precision and effectiveness of treatment, researchers hope to improve outcomes for patients with prostate cancer.

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

In this trial, participants will receive different combinations of treatments. Studies have shown that apalutamide, one of the treatments in this trial, significantly reduces the risk of death in prostate cancer patients when combined with hormone therapy (ADT). One study found that 65.1% of patients taking apalutamide with ADT were alive after 48 months, compared to 51.8% of those taking a placebo with ADT. Another treatment option in this trial is targeted radiation therapy. Research indicates that this therapy, when combined with hormone therapy, can help men with advanced prostate cancer live longer without disease progression. This combination has effectively kept PSA levels low, indicating reduced cancer activity. Together, these treatments aim to effectively manage prostate cancer that has spread beyond the pelvis. ^{6 7 8 9 10}

Who Is on the Research Team?

Neha Vapiwala

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Men with prostate cancer that has returned after surgery, evidenced by rising PSA levels. They must be suitable for standard radiation and hormone therapy, have no spread of cancer outside the pelvis as confirmed by imaging, and meet specific health criteria like adequate blood counts and liver function.

Inclusion Criteria

Hemoglobin (Hgb) >= 9.0 g/dL

I have not started hormone therapy for cancer return before my first PET scan.

Patient must not be enrolled in another therapeutic clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Patients undergo SOC PET/CT or PET/MR scan at baseline to determine PET status

1 week

1 visit (in-person)

Treatment

Patients receive standard of care external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) with or without apalutamide, and possibly metastasis-directed radiation therapy based on PET results

6 months

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 10 years

Every 3 months for 2 years, every 6 months for years 3-5, then annually for years 6-10

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide
• Targeted Radiation Therapy

Trial Overview The trial is testing if adding apalutamide (a drug blocking male hormones used by tumor cells) to standard care improves outcomes in patients whose prostate cancer has returned post-surgery. It also examines whether targeted radiation based on PET scan results offers additional benefits.

How Is the Trial Designed?

Group I: Arm D (EBRT, STAD, apalutamide, RT) Experimental Treatment 18 Interventions

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET positive for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A and apalutamide PO QD as in Arm B. Patients also undergo SBRT or 3D CRT, IMRT (including VMAT), and IMPT over 3-10 fractions in the absence of disease progression or unacceptable toxicity.

Group II: Arm C (EBRT, STAD, apalutamide) Experimental Treatment 13 Interventions

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET positive for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A. Patients also receive apalutamide PO QD as in Arm B.

Group III: Arm B (EBRT, STAD, apalutamide) Experimental Treatment 13 Interventions

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET negative for extra pelvic metastases undergo SOC EBRT and receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC as in Arm A. Patients also receive apalutamide PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

Group IV: Arm A (EBRT, short-term androgen deprivation therapy [STAD]) Active Control 12 Interventions

STEP 0: Patients undergo SOC PET/CT or PET/MR scan at baseline. Patients randomized to Arms C or D and receiving fluciclovine F18 IV undergo a repeat PET2 at time of PSA progression or clinical concerns for progression or 12 months after completion of enhanced systemic therapy, whichever occurs first. Patients in Arm C or D using another tracer for PET1 do not undergo PET2. STEP 1: Patients who are PET negative for extera pelvic metastases undergo SOC EBRT for 6 months. Patients also receive goserelin acetate SC, leuprolide acetate IM, triptorelin IM, relugolix PO, or degarelix SC for 6 months starting up to 3 months prior to EBRT but no later than 7 days after start of EBRT. All treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.

Apalutamide is already approved in United States, European Union for the following indications:

Approved in United States as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Erleada for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

In a study involving 57 patients with metastatic castration-resistant prostate cancer (mCRPC), the combination of apalutamide with abiraterone acetate and prednisone was well tolerated and demonstrated significant antitumor activity, particularly in patients who had not previously been treated with androgen receptor inhibitors.

While apalutamide reduced the systemic exposure to prednisone by 61%, no significant adverse events related to mineralocorticoid excess were observed, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Antitumor Effect of Apalutamide with Abiraterone Acetate plus Prednisone in Metastatic Castration-Resistant Prostate Cancer: Phase Ib Study. Posadas, EM., Chi, KN., de Wit, R., 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]

In the SPARTAN trial, apalutamide significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer (nmCRPC) receiving androgen-deprivation therapy, demonstrating its efficacy as a treatment option.

Apalutamide was generally well tolerated, with fatigue being the most common side effect, indicating a favorable safety profile while maintaining health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Al-Salama, ZT.[2020]

Apalutamide is an oral androgen receptor inhibitor that effectively blocks androgen effects, and it received its first global approval in February 2018 for treating non-metastatic castration-resistant prostate cancer (nmCRPC).

Currently, apalutamide is being tested in phase III trials for various prostate cancer stages, including metastatic castration-resistant prostate cancer and high-risk localized prostate cancer, indicating its potential for broader applications in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. Al-Salama, ZT.[2019]

Apalutamide, an oral medication for non-metastatic castration-resistant prostate cancer, can cause a range of skin reactions, including a rare lichenoid reaction, as demonstrated in a case study of a patient after 4 months of treatment.

This case highlights the importance of a multidisciplinary approach in identifying and managing drug-related adverse events, which can improve diagnosis and treatment strategies for patients experiencing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. Cremante, M., Puglisi, S., Gandini, A., et al.[2023]

In a phase III study (TITAN) involving men with metastatic castration-sensitive prostate cancer, adding apalutamide to androgen deprivation therapy significantly improved median radiographic progression-free survival and overall survival.

Apalutamide was found to maintain health-related quality of life and had a safety profile similar to that of placebo when combined with androgen deprivation therapy, expanding treatment options for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. Hoy, SM.[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/safety/

Safety | ERLEADA® (apalutamide) HCP Serious adverse reactions occurred in 20% of patients in the ERLEADA® + ADT arm and 20% of patients in the placebo + ADT arm.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5543693/

Safety and Antitumor Activity of Apalutamide (ARN-509) in ... Apalutamide was safe, well tolerated, and demonstrated clinical activity in mCRPC with 80% of AAP-naïve and 43% of post-AAP patients remaining on treatment for ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/210951s017lbl.pdf

ERLEADA® (apalutamide) tablets, for oral use In a randomized study (TITAN) of patients with metastatic castration-sensitive prostate cancer, fractures occurred in 9% of patients treated with ERLEADA and in ...

9. erleada.com erleada.com/

Official Patient Website | ERLEADA® (apalutamide) ERLEADA is a prescription medicine used to treat two types of prostate cancer: Prostate cancer that HAS SPREAD to other parts of the body and STILL responds to ...

10. innovativemedicine.jnj.com innovativemedicine.jnj.com/us/news-center/oncology/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 ...