Hormone + Radiation Therapy for Prostate Cancer

(HEATWAVE Trial)

Overseen By Christy Palodichuk

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Seizure threshold lowering drugs

Disqualifiers: Spinal cord compression, Prior pelvic radiation, Seizure history, 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

Compensation: Varies

Number of Visits: 9

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining hormone therapy with targeted radiation can more effectively treat prostate cancer. It uses apalutamide, a hormone therapy that blocks testosterone, along with precise radiation to target cancer cells. The goal is to determine if this combination can reduce tumor growth more effectively while minimizing harm to healthy tissue. Men with prostate cancer who have specific risk factors, such as certain PSA levels or visible tumors on an MRI, might be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, offering them a chance to contribute to significant advancements in prostate cancer treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications known to lower the seizure threshold at least 4 weeks before starting the study. If you are on medications that are CYP2D6 substrates with a narrow therapeutic index, you may need to switch to an alternative or reduce the dose.

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

Research has shown that apalutamide is generally safe and well tolerated. In previous studies with patients who have advanced prostate cancer, most continued treatment without serious problems. Among those new to apalutamide, 80% managed to stay on it without stopping due to side effects.

Image-guided stereotactic body radiation therapy (SBRT) is also considered a safe option for treating prostate cancer. This precise radiation targets tumors while minimizing harm to nearby healthy tissues. Some individuals might experience more urinary side effects, but overall, it remains a safe treatment.

Both treatments have been studied separately and have demonstrated promising safety results. However, individual experiences can vary, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining apalutamide with image-guided stereotactic body radiation therapy (SBRT) for prostate cancer because this approach offers a targeted attack on cancer cells. Unlike traditional hormone therapies that broadly suppress testosterone, apalutamide specifically blocks androgen receptors, which can help slow cancer growth more precisely. Additionally, the use of SBRT allows for high doses of radiation to be delivered accurately to the tumor in just a few sessions, potentially reducing treatment time and side effects compared to conventional radiation therapy. This combination could enhance the effectiveness of treatment while minimizing the impact on healthy tissue, providing new hope for patients.

What evidence suggests that combining apalutamide with image-guided SBRT could be effective for prostate cancer?

In this trial, participants will receive a combination of apalutamide and image-guided stereotactic body radiation therapy (SBRT). Research has shown that apalutamide effectively treats prostate cancer. Specifically, studies have demonstrated that patients using apalutamide with hormone therapy lived longer than those using only hormone therapy. For example, one study found that 65.1% of patients were alive after 48 months when taking apalutamide, compared to 51.8% who took a placebo.

Regarding SBRT, research indicates it is a safe and effective method for treating prostate cancer. SBRT delivers radiation with high precision, protecting healthy tissue while targeting tumors. This precision makes it a strong treatment option, with high rates of disease control and low recurrence chances.

Together, these treatments in this trial may offer a promising way to manage prostate cancer and improve patient outcomes. ^{2 3 6 7 8}

Who Is on the Research Team?

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Men aged 18+ with confirmed prostate adenocarcinoma, testosterone levels ≥150 ng/dL, and specific risk factors for prostate cancer. They must have undergone certain imaging tests and have adequate organ function. Excluded are those with spinal cord compression, prior pelvic malignancy or radiation, certain heart conditions within the past 6 months, seizure history or risks, uncontrolled hypertension, absorption-affecting GI disorders, active infections like HIV/hepatitis, or severe liver impairment.

Inclusion Criteria

Your AST or ALT levels are less than 2.5 times the upper limit of normal for screening.

Your glomerular filtration rate is 45 milliliters per minute or higher (at screening).

Your serum potassium level must be at least 3.5 mmol/L when evaluated prior to enrollment.

Exclusion Criteria

I have had cancer in my pelvic area before.

I have inflammatory bowel disease or an active connective tissue disorder.

I have a history of seizures or conditions that could lead to seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Hormonal Therapy

Participants receive apalutamide orally once daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months.

6-12 months

Monthly visits (in-person)

Radiation Therapy

Participants undergo image-guided stereotactic body radiation therapy (SBRT) for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1.

1-2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including multiparametric MRI and PSMA-PET/CT scans.

60 months

Every 3 months for the first 24 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Apalutamide
• Image-guided Stereotactic Body Radiation Therapy

Trial Overview The HEATWAVE trial is testing if hormone therapy using Apalutamide combined with image-guided Stereotactic Body Radiation Therapy (SBRT) can improve outcomes in men with prostate cancer. SBRT delivers precise high-dose radiation to tumors while sparing normal tissue. The goal is to see if this combination helps lower a marker called PSA which indicates disease cure.

How Is the Trial Designed?

Group I: Treatment (apalutamide, SBRT) Experimental Treatment 8 Interventions

Patients receive apalutamide PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 6 or 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo SBRT for 5 fractions over 1-2 weeks beginning on day 1 of cycle 1. Patients also undergo multiparametric MRI and collection of blood samples throughout the trial. Patients undergo PSMA-PET/CT scans during screening and follow up.

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?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

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

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 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]

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, an androgen receptor inhibitor for high-risk non-metastatic castration-resistant prostate cancer, shows rapid absorption and a large distribution volume, indicating effective body-wide delivery after oral administration.

In a study involving 1092 subjects, the pharmacokinetics of apalutamide and its metabolite were characterized, revealing low inter-individual variability and no significant predictors affecting drug clearance, suggesting consistent dosing effects across different patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. Pérez-Ruixo, C., Pérez-Blanco, JS., Chien, C., et al.[2021]

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]

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 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]

Citations

1. 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.

2. 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– ...

3. 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 ...

4. 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.

5. urotoday.com urotoday.com/video-lectures/mhspc/video/mediaitem/4763-real-world-data-explores-benefits-of-apalutamide-in-metastatic-hormone-sensitive-prostate-cancer-benjamin-maughan.html

Real-World Data Explores Benefits of Apalutamide in ... All doublet combinations showed superior outcomes compared to ADT monotherapy, with apalutamide demonstrating numerically superior results. Dr.

6. 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 ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0302283816301336

Phase 2 Study of the Safety and Antitumor Activity ... Apalutamide was safe and well tolerated in patients with high-risk nmCRPC in the phase 2 portion of the study. Apalutamide exhibited robust activity in ...

8. jnj.com jnj.com/media-center/press-releases/phase-2-data-for-erleada-apalutamide-plus-androgen-deprivation-therapy-following-radical-prostatectomy-in-patients-with-high-risk-localized-prostate-cancer-show-100-biochemical-free-recurrence-rate-more-than-two-years-post-surgery

Phase 2 data for ERLEADA® (apalutamide) plus androgen ... Following RP, patients who received the treatment regimen showed a 100% biochemical recurrence (BCR)–free rate at 24 months.