High Precision Stereotactic Radiotherapy to the Whole Prostate With Focal Boost and Varying Hormonal Therapy (HEATWAVE)
Overview
- Phase
- Phase 2
- Intervention
- Apalutamide
- Conditions
- Not specified
- Sponsor
- Jonsson Comprehensive Cancer Center
- Enrollment
- 95
- Locations
- 1
- Primary Endpoint
- Percent of patients achieving prostate specific antigen (PSA) of < 0.2 ng/mL
- Status
- Recruiting
- Last Updated
- 9 months ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed diagnosis of prostate adenocarcinoma
- •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)
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
Arms & Interventions
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.
Intervention: Apalutamide
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.
Intervention: Biospecimen Collection
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.
Intervention: Computed Tomography
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.
Intervention: Gallium Ga 68 Gozetotide
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.
Intervention: Guided Stereotactic Body Radiation Therapy
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.
Intervention: Multiparametric Magnetic Resonance Imaging
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.
Intervention: Positron Emission Tomography
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.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Time to biochemical recurrence (BCR)(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(24 months after completion of stereotactic body radiation therapy (SBRT))
- PROs on the EPIC-26 bowel domain(24 months after completion of SBRT)
- Radiographic persistence of disease on multiparametric magnetic resonance imaging(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(Up to 60 months)
- Radiographic persistence of disease on prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)(6 months after hormonal therapy completion)
- Physician-reported acute and late toxicities(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)