Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Adenocarcinoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Anti-Infective Agents

Anticoagulants

Bone Density Conservation Agents

Amino Acids

Gallium 68 PSMA-11

Hormones

Carbamide Peroxide

Edetic Acid

Pentetic Acid

Chelating Agents

Calcium

Calcium, Dietary

Radiopharmaceuticals

Lysine

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

Biospecimen Collection

Computed Tomography

Gallium Ga 68 Gozetotide

Guided Stereotactic Body Radiation Therapy

Multiparametric Magnetic Resonance Imaging

Positron Emission Tomography

Questionnaire Administration

Maria Casado

Amar Kishan

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.

PRIMARY OBJECTIVE:

I. To assess prostate specific antigen (PSA) complete response rates in patients with unfavorable intermediate risk prostate cancer who are receiving apalutamide monotherapy in conjunction with magnetic resonance imaging stereotactic body radiotherapy with precision dose-escalation and de-escalation to involved and uninvolved areas of the prostate, respectively.

SECONDARY OBJECTIVES:

I. Assessing time to biochemical recurrence (BCR; PSA ≥ nadir PSA + 2 ng/mL) among patients initially meeting primary endpoint.

II. Assessing patient-reported genitourinary quality of life, as assessed by the Expanded Prostate Cancer Index Composite-26 (EPIC-26) survey instrument 24 months after radiotherapy completion.

III. Assessing patient-reported bowel quality of life, as assessed by the EPIC-26 survey instrument 24 months after radiotherapy completion.

IV. Assessing radiographic persistence of disease on a prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) six months following hormonal therapy completion.

V. Assessing radiographic persistence of disease on a multiparametric MRI at fixed intervals (i.e., 6, 12, 18, 24, 30) months after radiotherapy completion.

VI. Assessment of longitudinal changes in patient-reported quality of life metrics on the EPIC-26 survey instrument.

VII. Physician-reported acute and late toxicities as per the Common Terminology Criteria for Adverse Events (CTCAE) scale version (v)5.0.

OUTLINE:

Patients receive apalutamide orally (PO) once daily (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.

After completion of study treatment, patients are followed up every 3 months for up to 24 months after SBRT and then up to 60 months after SBRT.

Hormone Therapy (Apalutamide) and Image-guided Stereotactic Body Radiation Therapy for the Treatment of Patients With Prostate Cancer, HEATWAVE Trial

High Precision Stereotactic Radiotherapy to the Whole Prostate With Focal Boost and Varying Hormonal Therapy (HEATWAVE)

Will be summarized by count and percent along with the 95% confidence interval. This will then be compared to the historical control rate of 70% using a two sample z test for proportions with a one-sided p-value threshold of 0.05.

Evaluated among patients initially meeting the primary endpoint. BCR is defined as PSA \>= nadir PSA + 2 ng/mL. Time to BCR will be reported descriptively for each patient. Five-year biochemical recurrence free survival will be estimated by the Kaplan-Meier method as well as descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum).

Changes will be analyzed with respect to whether they represent minimally important differences.

The analysis of both acute and late changes in the bowel domain of the EPIC instrument will be stratified for use of hydrogel spacers or not, as these may reduce both acute and late gastrointestinal bowel symptoms.

Defined by expert reader using the criterion of standardized uptake value within 20% of pre-SBRT PSMA PET/CT. Will be reported as a binary value (persistent versus not persistent).

Defined by expert reader using a composite of apparent diffusion coefficient, size, and ktrans. Will be reported as a binary value (persistent vs. not persistent).

For the EPIC-26 instrument, these will be represented by changes from baseline in the urinary incontinence, urinary obstruction, bowel, sexual function, and hormone/vitality domains. Changes will be analyzed with respect to whether they represent minimally important differences.

Evaluated per the Common Terminology Criteria for Adverse Events scale version 5.0. Rates will be reported descriptively. The 5-year cumulative incidences of late grade ≥ 2 genitourinary and gastrointestinal toxicity will be analyzed using a cumulative incidence framework. The analysis of gastrointestinal toxicities (acute and late) will be stratified by the use of hydrogel spacers.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Hormone Therapy (Apalutamide) and Image-guided Stereotactic Body Radiation Therapy for the Treatment of Patients With Prostate Cancer, HEATWAVE Trial	NCT06067269	Prostate Adenoc... Stage II Prosta... Stage IIIA Pros... Stage IIIB Pros...	Apalutamide Biospecimen Col... Computed Tomogr... Gallium Ga 68 G... Guided Stereota... Multiparametric... Positron Emissi... Questionnaire A...	18 Years -	Jonsson Comprehensive Cancer Center
Hormone Therapy (Apalutamide) and Image-guided Stereotactic Body Radiation Therapy for the Treatment of Patients With Prostate Cancer, HEATWAVE Trial	NCT06067269	Prostate Adenoc... Stage II Prosta... Stage IIIA Pros... Stage IIIB Pros...	Apalutamide Biospecimen Col... Computed Tomogr... Gallium Ga 68 G... Guided Stereota... Multiparametric... Positron Emissi... Questionnaire A...	18 Years -	Jonsson Comprehensive Cancer Center

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