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

Trial Summary

What is the purpose of this trial?

This phase II trial evaluates apalutamide in combination with image-guided stereotactic body radiation therapy (SBRT) for the treatment of patients with prostate cancer. Prostate cancer usually needs the hormone testosterone to grow. Apalutamide is a hormone therapy that blocks the effect of testosterone on prostate tumor cells. This may help stop the growth of tumor cells that need testosterone to grow. Image-guided SBRT is a standard treatment for some types of prostate cancer. This treatment combines imaging of cancer within the body, with the delivery of therapeutic radiation doses produced on a linear accelerator machine. SBRT uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Combining apalutamide with image-guided SBRT may increase a prostate cancer patient's chances of achieving an extremely low prostate specific antigen response, which is an early predictor of disease cure.

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.

What data supports the effectiveness of the drug Apalutamide in treating prostate cancer?

Apalutamide has been shown to significantly improve survival and delay disease progression in men with both metastatic castration-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer, while maintaining quality of life. ^{1 2 3 4 5}

Is the hormone and radiation therapy for prostate cancer safe for humans?

Apalutamide, used in hormone therapy for prostate cancer, is generally well tolerated, but common side effects include fatigue and skin reactions. It has been approved for use in various prostate cancer conditions, indicating a recognized safety profile. ^{1 2 4 5 6}

How does the drug Apalutamide combined with radiation therapy differ from other prostate cancer treatments?

This treatment is unique because it combines Apalutamide, a next-generation oral drug that blocks male hormones (androgens) from stimulating cancer growth, with advanced image-guided radiation therapy, potentially improving the effectiveness of radiation in treating prostate cancer. ^{1 2 3 4 7}

Research Team

Amar Kishan

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

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]

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]

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 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 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. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Apalutamide: First Global Approval. [2019]

3. England pubmed.ncbi.nlm.nih.gov

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

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Apalutamide and its Active Metabolite N-Desmethyl-Apalutamide in Healthy and Castration-Resistant Prostate Cancer Subjects. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. [2023]

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

Apalutamide radio-sensitisation of prostate cancer. [2023]