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

NCT ID: NCT06067269

Last Updated: 2025-07-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-28

Study Completion Date

2027-12-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Prostate Adenocarcinoma Stage II Prostate Cancer AJCC v8 Stage IIIA Prostate Cancer AJCC v8 Stage IIIB Prostate Cancer AJCC v8

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (apalutamide, SBRT)

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.

Group Type EXPERIMENTAL

Apalutamide

Intervention Type DRUG

Given PO

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Computed Tomography

Intervention Type PROCEDURE

Undergo PSMA-PET/CT

Gallium Ga 68 Gozetotide

Intervention Type OTHER

Undergo PSMA-PET/CT

Guided Stereotactic Body Radiation Therapy

Intervention Type RADIATION

Undergo guided SBRT

Multiparametric Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo multiparametric MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PSMA-PET/CT

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Apalutamide

Given PO

Intervention Type DRUG

Biospecimen Collection

Undergo collection of blood samples

Intervention Type PROCEDURE

Computed Tomography

Undergo PSMA-PET/CT

Intervention Type PROCEDURE

Gallium Ga 68 Gozetotide

Undergo PSMA-PET/CT

Intervention Type OTHER

Guided Stereotactic Body Radiation Therapy

Undergo guided SBRT

Intervention Type RADIATION

Multiparametric Magnetic Resonance Imaging

Undergo multiparametric MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PSMA-PET/CT

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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ARN 509 ARN-509 ARN509 Erleada JNJ 56021927 JNJ-56021927 Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68)Ga-labeled Glu-urea-Lys(Ahx)-HBED-CC (68)Ga-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC (68)Gallium-PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC (68Ga)Glu-urea-Lys(Ahx)-HBED-CC 68Ga-DKFZ-PSMA-11 68Ga-HBED-CC-PSMA 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC 68Ga-PSMA 68Ga-PSMA-11 68Ga-PSMA-HBED-CC [68Ga] Prostate-specific Membrane Antigen 11 [68Ga]GaPSMA-11 AAA 517 AAA-517 AAA517 Ga PSMA Ga-68 labeled DKFZ-PSMA-11 Ga-68 labeled PSMA-11 GA-68 PSMA-11 Gallium Ga 68 PSMA-11 Gallium Ga 68-labeled PSMA-11 GALLIUM GA-68 GOZETOTIDE Gallium-68 PSMA Gallium-68 PSMA Ligand Glu-urea-Lys(Ahx)-HBED-CC GaPSMA PSMA-HBED-CC GA-68 MP-MRI mpMRI Multi-parametric MRI Multiparametric MRI Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT

Eligibility Criteria

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Inclusion Criteria

* Confirmed diagnosis of prostate adenocarcinoma
* Age ≥ 18
* Classified as having National Comprehensive Cancer Network unfavorable intermediate risk prostate cancer (i.e., \[a\] 2 of the following: PSA 10-20 ng/mL, clinical T category 2b-2c, or International Society of Urological Pathology \[ISUP\] grade group 2; \[b\] OR any 1 of \[a\] with ISUP grade group 3 disease; OR \[c\] any 1 of \[a\] with 50% or more cores on systematic biopsy showing prostate cancer)
* Have a Decipher genomic classifier score
* Have at least one dominant intraprostatic lesion visible on multiparametric MRI (Prostate Imaging-Reporting and Data System \[PI-RADS\] version 2.1 score 4 or 5)
* Have underwent a prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)
* Have total testosterone \>= 150 ng/dL
* Adequate performance status (Eastern Cooperative Oncology Group \[ECOG\] 0-1)
* Hemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization (at screening)
* Platelet count ≥ 100,000 x 10\^9/uL independent of transfusion and/or growth factors within 3 months prior to randomization (at screening)
* Serum albumin ≥ 3.0 g/dL (at screening)
* Glomerular filtration rate (GFR) ≥ 45 mL/min (at screening)
* Serum potassium ≥ 3.5 mmol/L (at screening)
* Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible) (at screening)
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 2.5 x ULN (at screening)
* Medications known to lower the seizure threshold (see list under prohibited medications) must be discontinued or substituted at least 4 weeks prior to study entry

Exclusion Criteria

* Any evidence of spinal cord compression (radiological or clinical)
* Prior pelvic malignancy
* Prior pelvic radiation
* Concurrent malignancy other than adequately treated basal cell or squamous cell skin cancer, non-muscle invasive bladder cancer (NMIBC), or any other cancer in situ currently without evidence of recurrence or progression
* Inability to undergo radiotherapy, or hormonal therapy
* Primary small cell carcinoma of the prostate (prostate adenocarcinoma with neuroendocrine differentiation is allowed)
* Inflammatory bowel disease or active collagen vascular disease
* History of any of the following:

* Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system \[CNS\] or meningeal disease which may require treatment with surgery or radiation therapy)
* Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
* Current evidence of any of the following:

* Uncontrolled hypertension
* Gastrointestinal disorder affecting absorption
* Known active infection (eg, human immunodeficiency virus \[HIV\] or viral hepatitis)
* Any condition that in the opinion of the investigator would preclude participation in this study
* Treatment with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, a dose reduction of the CYP2D6 substrate may be considered
* Baseline moderate and severe hepatic impairment (Child Pugh class B \& C)
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amar Kishan

Role: PRINCIPAL_INVESTIGATOR

UCLA / Jonsson Comprehensive Cancer Center

Locations

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UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Christy Palodichuk

Role: CONTACT

310-267-8988

Facility Contacts

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Maria Casado

Role: primary

310-794-6913

Other Identifiers

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NCI-2023-06647

Identifier Type: REGISTRY

Identifier Source: secondary_id

23-000429

Identifier Type: -

Identifier Source: org_study_id

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