- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06067269
Hormone Therapy (Apalutamide) and Image-guided Stereotactic Body Radiation Therapy for the Treatment of Patients With Prostate Cancer, HEATWAVE Trial (HEATWAVE)
High Precision Stereotactic Radiotherapy to the Whole Prostate With Focal Boost and Varying Hormonal Therapy (HEATWAVE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90095
- UCLA / Jonsson Comprehensive Cancer Center
-
Principal Investigator:
- Amar Kishan
-
Contact:
- Amar Kishan
- Phone Number: 310-825-6577
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Ancillary studies
Undergo collection of blood samples
Other Names:
Given PO
Other Names:
Undergo multiparametric MRI
Other Names:
Undergo PSMA-PET/CT
Other Names:
Undergo PSMA-PET/CT
Other Names:
Undergo PSMA-PET/CT
Other Names:
Undergo guided SBRT
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent of patients achieving prostate specific antigen (PSA) of < 0.2 ng/mL
Time Frame: Three months after completion of apalutamide
|
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.
|
Three months after completion of apalutamide
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to biochemical recurrence (BCR)
Time Frame: We will follow patients for five years following completion of radiotherapy. Biochemical disease status will be checked every 3 months for the first year, and every 6 months thereafter.
|
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).
|
We will follow patients for five years following completion of radiotherapy. Biochemical disease status will be checked every 3 months for the first year, and every 6 months thereafter.
|
Patient-reported outcomes (PROs) on the Expanded Prostate Cancer Index Composite-26 (EPIC-26) urinary domain
Time Frame: 24 months after completion of stereotactic body radiation therapy (SBRT)
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Changes will be analyzed with respect to whether they represent minimally important differences.
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24 months after completion of stereotactic body radiation therapy (SBRT)
|
PROs on the EPIC-26 bowel domain
Time Frame: 24 months after completion of SBRT
|
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.
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24 months after completion of SBRT
|
Radiographic persistence of disease on prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)
Time Frame: 6 months after hormonal therapy completion
|
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).
|
6 months after hormonal therapy completion
|
Radiographic persistence of disease on multiparametric magnetic resonance imaging
Time Frame: At 6 months, 12 months, 18 months, 24 and 30 months after radiotherapy completion
|
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).
|
At 6 months, 12 months, 18 months, 24 and 30 months after radiotherapy completion
|
Longitudinal PROs on the EPIC-26 questionnaire in the sexual, urinary, and bowel domains
Time Frame: Up to 60 months
|
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.
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Up to 60 months
|
Physician-reported acute and late toxicities
Time Frame: We will follow patients for five years following completion of radiotherapy. Acute toxicity will be scored within the first 90 days after radiation. Late toxicity and patient-reported outcomes will be assessed every 3 months for the first year, and every
|
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.
|
We will follow patients for five years following completion of radiotherapy. Acute toxicity will be scored within the first 90 days after radiation. Late toxicity and patient-reported outcomes will be assessed every 3 months for the first year, and every
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Amar Kishan, UCLA / Jonsson Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Radiopharmaceuticals
- Anticoagulants
- Chelating Agents
- Sequestering Agents
- Calcium Chelating Agents
- Edetic Acid
- Gallium 68 PSMA-11
Other Study ID Numbers
- 23-000429
- NCI-2023-06647 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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