Hormone + Radiation Therapy for Prostate Cancer

(HEATWAVE Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Amar Kishan

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

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.

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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.

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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.

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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.

Trial 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

Participant Groups

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UCLA / Jonsson Comprehensive Cancer Center Los Angeles, CA

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center Lead Sponsor

Janssen Scientific Affairs, LLC Industry Sponsor

References

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

Apalutamide: A Review in Metastatic Castration-Sensitive Prostate Cancer. [2021] Apalutamide (Erleada®) is an oral selective androgen receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. It is approved in the EU and the USA for the treatment of adult men with metastatic castration-sensitive prostate cancer (mCSPC). In a multinational, phase III study (TITAN) in this patient population, the addition of apalutamide (240 mg once daily) to androgen deprivation therapy (ADT) significantly improved median radiographic progression-free survival (rPFS), median overall survival (OS) and the median time to cytotoxic chemotherapy, while maintaining health-related quality of life (HR-QOL) and not substantially differing from placebo plus ADT in safety. Although mature OS data are awaited with interest, the addition of apalutamide to ADT extends the treatment options available for standard of care in adult men with mCSPC.

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

Apalutamide: First Global Approval. [2019] Apalutamide (ErleadaTM) is a next-generation oral androgen receptor (AR) inhibitor that is being developed by Janssen for the treatment of prostate cancer (PC). It binds directly to the ligand-binding domain of the AR and blocks the effects of androgens. In February 2018, apalutamide received its first global approval in the USA for the treatment of non-metastatic castration-resistant PC (nmCRPC). Apalutamide is undergoing phase III investigation in chemotherapy-naive patients with metastatic CRPC (in combination with abiraterone acetate plus prednisone), patients with high-risk localized or locally advanced PC receiving primary radiation therapy, and in patients with metastatic hormone-sensitive PC and biochemically-relapsed PC. This article summarizes the milestones in the development of apalutamide leading to this first approval in nmCRPC.

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

Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy. [2021] Apalutamide, a competent inhibitor of the androgen receptor, has shown promising clinical efficacy results for patients with advanced prostate cancer. Here, we describe the rationale and design for the SAVE trial, a multi-center, Phase II study, wherein 202 men with biochemical progression after radical prostatectomy are randomly assigned 1:1 to apalutamide plus salvage radiotherapy (SRT) or androgen-deprivation therapy with an luteinizing hormone-releasing hormone agonist or antagonist plus SRT. The primary objective is to compare sexual function between the two treatment arms based on the expanded prostate cancer index-26 sexual domain score at nine months after start of hormonal treatment. The key secondary objectives are to assess quality of life, to evaluate the safety profile and the short-term efficacy of apalutamide in combination with SRT. ClinicalTrials.gov identifier: NCT03899077.

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

Apalutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2020] Apalutamide (marketed as Erleada®) is an oral non-steroidal next-generation selective inhibitor of the androgen receptor (AR), and is approved in several countries, including the USA and those of the EU, for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In men with nmCRPC who were receiving androgen-deprivation therapy (ADT) and had a high risk of metastases in SPARTAN, apalutamide significantly prolonged metastasis-free survival (MFS) compared with placebo, with consistent benefits demonstrated across subgroups. The addition of apalutamide to ongoing ADT significantly prolonged time to metastasis and progression-free survival (PFS) compared with placebo, and maintained health-related quality of life (HR-QOL). Apalutamide was generally well tolerated in SPARTAN, with fatigue being the most frequently reported adverse event. Given the available evidence, apalutamide with ongoing ADT represents an emerging treatment option for patients with nmCRPC who are at high risk of developing metastatic disease.

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] Apalutamide is a next-generation androgen receptor inhibitor approved for treatment of subjects with high-risk, non-metastatic, castration-resistant prostate cancer (NM-CRPC).

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

Apalutamide-induced lichenoid reaction in a patient with non-metastatic castrate-resistant prostate cancer. [2023] Apalutamide is an oral selective androgen receptor inhibitor, approved by the FDA for the treatment of patients with non-metastatic, castration-resistant prostate cancer (M0 CRPC) at high risk of developing metastases and for patients with metastatic castration-sensitive prostate (mHSPC) in association with androgen deprivation therapy (ADT). In the registration studies, skin reactions were reported among the most common side effects and as an adverse event of special interest.

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

Apalutamide radio-sensitisation of prostate cancer. [2023] The combination of radiotherapy with bicalutamide is the standard treatment of prostate cancer patients with high-risk or locally advanced disease. Whether new-generation anti-androgens, like apalutamide, can improve the radio-curability of these patients is an emerging challenge.