Description:
This phase II trial studies how well antiandrogen therapy (leuprolide, apalutamide, and
abiraterone acetate) and stereotactic body radiation therapy (SBRT) works in treating
patients with prostate cancer that has come back and has spread to other parts of the body.
Drugs used in chemotherapy, such as leuprolide, apalutamide, and abiraterone acetate, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. SBRT uses special equipment to
position a patient and deliver radiation to tumors with high precision. This method can kill
tumor cells with fewer doses over a shorter period and cause less damage to normal tissue.
Giving antiandrogen therapy and SBRT may work better in treating patients with prostate
cancer.
Title
- Brief Title: Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer
- Official Title: A Single-Arm, Open-Label, Phase II Study of Systemic and Tumor Directed Therapy for Recurrent Oligometastatic M1 Prostate Cancer
Clinical Trial IDs
- ORG STUDY ID:
18-001037
- SECONDARY ID:
NCI-2019-00337
- NCT ID:
NCT03902951
Conditions
- Metastatic Prostate Adenocarcinoma
- Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation
- Recurrent Prostate Carcinoma
- Stage IVB Prostate Cancer AJCC v8
Interventions
Drug | Synonyms | Arms |
---|
Abiraterone Acetate | CB7630, Zytiga | Treatment (leuprolide, apalutamide, abiraterone acetate, SBRT) |
Apalutamide | ARN 509, ARN-509, ARN509, JNJ 56021927, JNJ-56021927 | Treatment (leuprolide, apalutamide, abiraterone acetate, SBRT) |
Leuprolide Acetate | A-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, Viadur | Treatment (leuprolide, apalutamide, abiraterone acetate, SBRT) |
Purpose
This phase II trial studies how well antiandrogen therapy (leuprolide, apalutamide, and
abiraterone acetate) and stereotactic body radiation therapy (SBRT) works in treating
patients with prostate cancer that has come back and has spread to other parts of the body.
Drugs used in chemotherapy, such as leuprolide, apalutamide, and abiraterone acetate, work in
different ways to stop the growth of tumor cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. SBRT uses special equipment to
position a patient and deliver radiation to tumors with high precision. This method can kill
tumor cells with fewer doses over a shorter period and cause less damage to normal tissue.
Giving antiandrogen therapy and SBRT may work better in treating patients with prostate
cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To assess the efficacy of combined systemic and tumor directed therapy for recurrent
oligometastatic M1a,b prostate cancer patients with 1-5 metastases (exclusive of pelvic nodal
N1 metastases) staged by prostate-specific membrane antigen (PSMA) positron emission
tomography (PET)-computed tomography (CT).
SECONDARY OBJECTIVES:
I. Time to biochemical progression. II. Time to additional antineoplastic therapy. III.
Prostate cancer specific survival. IV. Safety and tolerability. V. Assessment of health
related quality of life using the Functional Assessment of Cancer Therapy - Prostate (FACT-P)
scale.
CORRELATIVE OBJECTIVES:
I. To determine genomic and transcriptomic features present in metastatic tumors in patients
that respond to this multimodal therapy.
II. To evaluate biomarkers of response using circulating tumor cells (CTCs). III. To evaluate
biomarkers of response using circulating tumor deoxyribonucleic acid (DNA) (ctDNA).
IV. To evaluate immunophenotypes of circulating immune cells.
OUTLINE:
Patients receive a single dose of leuprolide subcutaneously (SC) on day 1 and apalutamide
orally (PO) once daily (QD) and abiraterone acetate PO QD for up to 6 months in the absence
of disease progression or unacceptable toxicity. Beginning 2 months of initiation of
antiandrogen therapy (ADT), patients also receive SBRT over 1, 3, or 5 fractions in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 2 -4 weeks, every 30
days for 6 months, and then every 3 months thereafter.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (leuprolide, apalutamide, abiraterone acetate, SBRT) | Experimental | Patients receive leuprolide SC on day 1, Patients receive a single dose of leuprolide SC on day 1 and apalutamide PO QD and abiraterone acetate PO QD for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning 2 months of initiation of ADT, patients also receive SBRT over 1, 3, or 5 fractions in the absence of disease progression or unacceptable toxicity. | - Abiraterone Acetate
- Apalutamide
- Leuprolide Acetate
|
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of prostate adenocarcinoma after radical prostatectomy (primary
small cell carcinoma of the prostate is not allowed, however adenocarcinoma with
neuroendocrine differentiation is allowed)
- Presence of 1-5 visible metastases (by PSMA PET-CT)
- At least one metastasis must be M1a-b
- Visceral metastases are not allowed
- Patients may have any number of pelvic nodal metastases (but largest must be < 2
cm)
- Metastases must be amenable to treatment with SBRT
- Biopsy of one metastasis must be attempted, unless unsafe to perform
- Patient must be fit to undergo SBRT to all visible sites of metastases, ADT
- Total testosterone > 150 ng/dL prior to ADT (optimal time to measure total
testosterone is between 8 and 9 am)
- 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
- Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors
within 3 months prior to randomization
- Serum albumin >= 3.0 g/dL
- Glomerular filtration rate (GFR) >= 45 mL/min
- Serum potassium >= 3.5 mmol/L
- Serum total bilirubin =< 1.5 x upper limits 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
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x ULN
- Medications known to lower the seizure threshold 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 aside from salvage prostate radiation
- Concurrent malignancy aside from superficial skin cancers or superficial bladder
tumors
- Inability to undergo radiotherapy, or ADT
- 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
- Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)
- Any chronic medical condition requiring a higher dose of corticosteroid than 10
mg prednisone/prednisolone once daily
- Any condition that in the opinion of the investigator would preclude
participation in this study
- Concomitant strong CYP3A4 inducers. (If a strong CYP3A4 inducer must be
co-administered, abiraterone acetate dose frequency will be adjusted). [SAFETY:
Warning against use with CYP2C8 inhibitors with narrow therapeutic index is also
pertinent to be included as it is also part of United States Prescribing
Information (USPI): In a CYP2C8 drug-drug interaction trial in healthy subjects,
the area under curve (AUC) of pioglitazone (CYP2C8 substrate) was increased by
46% when pioglitazone was given together with a single dose of 1,000 mg
abiraterone acetate. Therefore, patients should be monitored closely for signs of
toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used
concomitantly with ZYTIGA]
- 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 (ChildPugh Class B & C)
- Presence of visceral metastases (i.e., stage M1c)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percent of patients achieving a serum prostate specific antigen (PSA) of < 0.05 ng/mL |
Time Frame: | Up to 6 months post treatment |
Safety Issue: | |
Description: | Will be summarized by count and percent along with the 95% confidence interval. |
Secondary Outcome Measures
Measure: | Time to biochemical progression |
Time Frame: | Baseline to first rise in PSA to 0.2 ng/mL, assessed up to 2 years |
Safety Issue: | |
Description: | Will be summarized using Kaplan-Meier method. |
Measure: | Time to radiographic progression |
Time Frame: | Baseline to time when any imaging shows new evidence of metastatic disease, assessed up to 2 years |
Safety Issue: | |
Description: | Will be summarized using Kaplan-Meier method. |
Measure: | Time to initiation of alternative antineoplastic therapy |
Time Frame: | Baseline to time when new anti-prostate cancer therapy is initiated, assessed up to 2 years |
Safety Issue: | |
Description: | Will be summarized using Kaplan-Meier method. |
Measure: | Prostate cancer specific survival |
Time Frame: | Up to 2 years post treatment |
Safety Issue: | |
Description: | |
Measure: | Health related quality of life: Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire |
Time Frame: | Up to 2 years post treatment |
Safety Issue: | |
Description: | This uses the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaire. It assesses patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Items are rated on a 0 to 4 Likert type scale and combined to produce subscale scores for each domain and a global score, the higher the score, the better the quality of life. Range from 0-150 . Data will be aggregated per patient and over time. |
Measure: | Incidence of adverse events |
Time Frame: | Up to 30 days post treatment |
Safety Issue: | |
Description: | The intensity of clinical adverse events will be graded according to the Common Terminology Criteria for Adverse Events version (v) 4.0 (CTCAE) grading system in the toxicity categories. |
Measure: | Biomarker analysis |
Time Frame: | Up to 2 years post treatment |
Safety Issue: | |
Description: | Will conduct whole exome deep sequencing (WES), RNA sequencing (RNA-seq), and comparative genomic hybridizations (CGH) of the metastatic tumors. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Jonsson Comprehensive Cancer Center |
Last Updated
August 12, 2021