Metastatic Prostate AdenocarcinomaPhase 2NCT03902951
Antiandrogen Therapy and SBRT in Treating Patients With Recurrent, Metastatic Prostate Cancer
A Phase 2 study testing Abiraterone Acetate, Apalutamide and Leuprolide Acetate in people with Metastatic Prostate Adenocarcinoma and Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Prostate Adenocarcinoma, Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation, Recurrent Prostate Carcinoma
- What is being tested?
- Abiraterone Acetate, Apalutamide and Leuprolide Acetate
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2021to 1 Jan 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
About this study
Official title: A Single-Arm, Open-Label, Phase II Study of Systemic and Tumor Directed Therapy for Recurrent Oligometastatic M1 Prostate Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- Conditions
- Metastatic Prostate Adenocarcinoma, Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation, Recurrent Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8
- Being tested
- Abiraterone Acetate, Apalutamide, Leuprolide Acetate, Quality-of-Life Assessment, Questionnaire Administration
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abiraterone AcetateDrug
Also called CB7630, Zytiga
Given PO
ApalutamideDrug
Also called ARN 509, ARN-509, ARN509, JNJ 56021927
Given PO
Leuprolide AcetateDrug
Also called A-43818, Abbott 43818, Abbott-43818, Carcinil
Given SC
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
Stereotactic Body Radiation TherapyRadiation
Also called SABR, SBRT, Stereotactic Ablative Body Radiation Therapy
Undergo SBRT
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Abiraterone Acetate; Drug: Apalutamide; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Stereotactic Body Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of patients achieving a serum prostate specific antigen (PSA) of < 0.05 ng/mL
Will be summarized by count and percent along with the 95% confidence interval.
Measured: Up to 6 months post treatment
Secondary outcomes (7)
Time to biochemical progression
Will be summarized using Kaplan-Meier method.
Measured: Baseline to first rise in PSA to 0.2 ng/mL, assessed up to 2 years
Time to radiographic progression
Will be summarized using Kaplan-Meier method.
Measured: Baseline to time when any imaging shows new evidence of metastatic disease, assessed up to 2 years
Time to initiation of alternative antineoplastic therapy
Will be summarized using Kaplan-Meier method.
Measured: Baseline to time when new anti-prostate cancer therapy is initiated, assessed up to 2 years
Prostate cancer specific survival
Measured: Up to 2 years post treatment
Health related quality of life: Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire
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.
Measured: Up to 2 years post treatment
Incidence of adverse events
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.
Measured: Up to 30 days post treatment
Biomarker analysis
Will conduct whole exome deep sequencing (WES), RNA sequencing (RNA-seq), and comparative genomic hybridizations (CGH) of the metastatic tumors.
Measured: Up to 2 years post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study start17 Mar 2021
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Prostate AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Inc.
- Responsible party
- Sponsor
- Investigators
- Amar Kishan, Principal investigator, UCLA / Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03902951
- Sponsor's protocol ID
- 18-001037
- Other IDs
- NCI-2019-00337
- Status last verified
- Feb 2026
- First submitted
- 3 Apr 2019
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
Nikitas J, Rettig M, Shen J, Reiter R, Lee A, Steinberg ML, Valle LF, Sachdeva A, Romero T, Calais J, Czernin J, Nickols NG, Kishan AU. Systemic and Tumor-directed Therapy for Oligorecurrent Metastatic Prostate Cancer (SATURN): Primary Endpoint Results from a Phase 2 Clinical Trial. Eur Urol. 2024 Jun;85(6):517-520. doi: 10.1016/j.eururo.2024.01.021. Epub 2024 Mar 16.
PubMed 38494380