- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03902951
Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer
A Single-Arm, Open-Label, Phase II Study of Systemic and Tumor Directed Therapy for Recurrent Oligometastatic M1 Prostate Cancer
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90095
- UCLA / Jonsson Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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)
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 (leuprolide, apalutamide, abiraterone acetate, SBRT)
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.
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Ancillary studies
Other Names:
Ancillary studies
Given PO
Other Names:
Undergo SBRT
Other Names:
Given PO
Other Names:
Given SC
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent of patients achieving a serum prostate specific antigen (PSA) of < 0.05 ng/mL
Time Frame: Up to 6 months post treatment
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Will be summarized by count and percent along with the 95% confidence interval.
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Up to 6 months post treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to biochemical progression
Time Frame: Baseline to first rise in PSA to 0.2 ng/mL, assessed up to 2 years
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Will be summarized using Kaplan-Meier method.
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Baseline to first rise in PSA to 0.2 ng/mL, assessed up to 2 years
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Time to radiographic progression
Time Frame: Baseline to time when any imaging shows new evidence of metastatic disease, assessed up to 2 years
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Will be summarized using Kaplan-Meier method.
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Baseline to time when any imaging shows new evidence of metastatic disease, assessed up to 2 years
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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
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Will be summarized using Kaplan-Meier method.
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Baseline to time when new anti-prostate cancer therapy is initiated, assessed up to 2 years
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Prostate cancer specific survival
Time Frame: Up to 2 years post treatment
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Up to 2 years post treatment
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Health related quality of life: Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire
Time Frame: Up to 2 years post treatment
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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.
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Up to 2 years post treatment
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Incidence of adverse events
Time Frame: Up to 30 days post treatment
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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.
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Up to 30 days post treatment
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Biomarker analysis
Time Frame: Up to 2 years post treatment
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Will conduct whole exome deep sequencing (WES), RNA sequencing (RNA-seq), and comparative genomic hybridizations (CGH) of the metastatic tumors.
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Up to 2 years post treatment
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Genomic and transcriptomic features present in metastatic tumors
Time Frame: Up to 2 years post treatment
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Will conduct whole exome deep sequencing (WES), ribonucleic acid (RNA) sequencing (RNA-seq), and comparative genomic hybridizations (CGH) of the metastatic tumors of the 28 patients enrolled in the Phase II trial.
Then, will identify discriminating features of the metastatic tumors in responders that distinguish them from the non-responders.
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Up to 2 years post treatment
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Circulating tumor deoxyribonucleic acid (ctDNA) for predictors of response
Time Frame: Up to 2 years post treatment
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Up to 2 years post treatment
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Circulating tumor cells (CTCs) for predictors of response
Time Frame: Up to 2 years post treatment
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Up to 2 years post treatment
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Changes in circulating immunophenotypes
Time Frame: Baseline up to 2 years post treatment
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Baseline up to 2 years post treatment
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Amar Kishan, UCLA / Jonsson Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
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 (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Recurrence
- Adenocarcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Steroid Synthesis Inhibitors
- Reproductive Control Agents
- Fertility Agents, Female
- Fertility Agents
- Leuprolide
- Abiraterone Acetate
Other Study ID Numbers
- 18-001037
- NCI-2019-00337 (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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