Newly Diagnosed Oligometastatic Prostate Cancer
Conditions
Keywords
oligometastatic, SBRT, abiraterone, apalutamide
Brief summary
This is a trial for patients with newly diagnosed metastatic prostate cancer with 5 or fewer sites of metastases. The trial involves surgery (removal of the prostate) or radiation to the prostate, six months of hormone therapy, and stereotactic body radiotherapy to the sites of metastasis.
Detailed description
This is a single arm Phase II clinical trial in patients with newly diagnosed M1a,b prostate cancer and 1-5 radiographically visible metastases treated with radical prostatectomy (and post-operative fractionated radiotherapy for pT 3a, pN1, or positive margins) or radiation to the prostate, metastasis directed SBRT, and complete ADT with LHRH analog leuprolide, abiraterone acetate with prednisone, and apalutamide (ARN-509) for a total of six months of systemic therapy. The primary endpoint of our study is the percent of patients achieving a serum PSA of \<0.05 ng/mL six months after recovery of serum testosterone (for patients undergoing radical prostatectomy) or PSA \<nadir+2 (for patients undergoing prostate radiation).
Interventions
PROCEDUREradical prostatectomy
surgical removal of the prostate
RADIATIONstereotactic body radiotherapy
Highly targeted radiation
DRUGLeuprolide
Lowers serum testosterone
DRUGapalutamide
antiandrogen
DRUGabiraterone
Inhibits androgen synthesis
Sponsors
VA Office of Research and Development
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm Phase II clinical trial
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Biopsy confirmed diagnosis of prostate adenocarcinoma (primary small cell carcinoma of the prostate is not allowed, however adenocarcinoma with neuroendocrine differentiation is allowed) 2. Age 18 3. Presence of 1-5 visible metastases (by NaF PET-CT or PSMA PET-CT including diagnostic CT of the chest, abdomen, and pelvis) 1. At least one metastasis must be M1a-b 2. Visceral metastases are not allowed 3. Patients may have any number of pelvic nodal metastases (but largest must be \<2 cm) 4. Metastases must be amenable to treatment with SBRT 5. Biopsy of one metastasis must be attempted, unless unsafe to perform. If biopsy is not diagnostic, or unsafe to perform, then a secondary imaging modality (for example, MRI) must also be consistent with metastatic disease (unless PSMA PET-CT was used as initial staging). 4. Patient must be fit to undergo radical prostatectomy, SBRT to all visible sites of metastases, ADT, 5. Total testosterone \>200 ng/dL prior to ADT (optimal time to measure total testosterone is between 8 and 9 am) 6. Adequate performance status (ECOG 0-1) 7. Clinical laboratory values at screening: 1. Hemoglobin 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization 2. Platelet count 100,000 x 109/ L independent of transfusion and/or growth factors within 3 months prior to randomization 3. Serum albumin 3.0 g/dL 4. GFR 45 mL/min 5. Serum potassium 3.5 mmol/L 6. Serum total bilirubin 1.5 ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is \>1.5 ULN, measure direct and indirect bilirubin and if direct bilirubin is 1.5 ULN, subject may be eligible) 7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \<2.5 ULN 8. 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
1. Any evidence of spinal cord compression (radiological or clinical) 2. Prior pelvic malignancy 3. Prior pelvic radiation 4. Concurrent malignancy aside from superficial skin cancers or superficial bladder tumors 5. Inability to undergo prostatectomy, radiotherapy, or ADT 6. Primary small cell carcinoma of the prostate (prostate adenocarcinoma with neuroendocrine differentiation is allowed) 7. Inflammatory bowel disease or active collagen vascular disease 8. History of any of the following: 1. Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy) 2. 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 9. Current evidence of any of the following: 1. Uncontrolled hypertension 2. Gastrointestinal disorder affecting absorption 3. Active infection (eg, human immunodeficiency virus \[HIV\] or viral hepatitis) 4. Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily 5. Any condition that in the opinion of the investigator would preclude participation in this study 6. Concomitant strong CYP3A4 inducers. (If a strong CYP3A4 inducer must be co-administered, abiraterone acetate dose frequency will be adjusted). 7. 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. 8. Baseline severe hepatic impairment (ChildPugh Class B & C) 10. Presence of visceral metastases (i.e., stage M1c)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With PSA<0.05ng/mL (Radical Prostatectomy) or PSA <Nadir+2ng/mL (Prostate Radiation) | 6 months after recovery of testosterone | PSA is a biomarker for disease burden in prostate adenocarcinoma and offers a non-invasive and sensitive assessment of disease control after treatment in the vast majority of patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Biochemical Progression | up to 5 years | biochemical, radiographic, or clinical |
| Time to Radiographic Progression | up to 5 years | per PCWG3 criteria |
| Number of Participants With Treatment-related Adverse Events as Assessed by Physician Using CTCAE v4.0 Criteria | up to 5 years | CTCAE v4 criteria are a set of criteria for the standardized classification of adverse effects cancer therapy. The CTCAE system is a product of the US National Cancer Institute. The criteria are assessed by physician. The grades range from 0 to 5 (higher is worse). Data will be aggregated per patient and over time and classified by organ system (e.g., genitourinary, gastrointestinal, etc). |
| Prostate Cancer Specific Survival | up to 5 years | Prostate cancer specific survival |
| Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Every 3 months up to a total of 21 months | 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 sub-scores that are summed into a total FACT-P score, the higher the score, the better the quality of life. Range from 0-150 . Data was aggregated per patient and over time. Data represented here are the mean scores and 95% confidence intervals of the participants who filled out the questionnaire (15/24 completed through 18 months, 12/24 completed through 21 months). |
| Time to Initiation of Additional Antineoplastic Therapy | up to 5 years | antineoplastic therapy includes any systemic or focal anti-prostate cancer therapy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Arm Radical prostatectomy (and post-operative fractionated radiotherapy for pT=3a, pN1, or positive margins), metastasis directed SBRT, and complete ADT with LHRH analog leuprolide, abiraterone acetate with prednisone, and apalutamide (ARN-509) for a total of six months of systemic therapy.
radical prostatectomy: surgical removal of the prostate
stereotactic body radiotherapy: Highly targeted radiation
Leuprolide: Lowers serum testosterone
apalutamide: antiandrogen
abiraterone: Inhibits androgen synthesis | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Experimental Arm |
|---|---|
| Age, Continuous | 69 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment United States | 28 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 21 / 28 |
| serious Total, serious adverse events | 1 / 28 |
Outcome results
Primary
Percentage of Participants With PSA<0.05ng/mL (Radical Prostatectomy) or PSA <Nadir+2ng/mL (Prostate Radiation)
PSA is a biomarker for disease burden in prostate adenocarcinoma and offers a non-invasive and sensitive assessment of disease control after treatment in the vast majority of patients.
Time frame: 6 months after recovery of testosterone
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm | Percentage of Participants With PSA<0.05ng/mL (Radical Prostatectomy) or PSA <Nadir+2ng/mL (Prostate Radiation) | 20 Participants |
Secondary
Number of Participants With Treatment-related Adverse Events as Assessed by Physician Using CTCAE v4.0 Criteria
CTCAE v4 criteria are a set of criteria for the standardized classification of adverse effects cancer therapy. The CTCAE system is a product of the US National Cancer Institute. The criteria are assessed by physician. The grades range from 0 to 5 (higher is worse). Data will be aggregated per patient and over time and classified by organ system (e.g., genitourinary, gastrointestinal, etc).
Time frame: up to 5 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental Arm | Number of Participants With Treatment-related Adverse Events as Assessed by Physician Using CTCAE v4.0 Criteria | Grade 2 | 19 Participants |
| Experimental Arm | Number of Participants With Treatment-related Adverse Events as Assessed by Physician Using CTCAE v4.0 Criteria | Grade 3 | 2 Participants |
| Experimental Arm | Number of Participants With Treatment-related Adverse Events as Assessed by Physician Using CTCAE v4.0 Criteria | Grade 4 | 1 Participants |
Secondary
Patient Reported Outcomes as Assessed by 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 sub-scores that are summed into a total FACT-P score, the higher the score, the better the quality of life. Range from 0-150 . Data was aggregated per patient and over time. Data represented here are the mean scores and 95% confidence intervals of the participants who filled out the questionnaire (15/24 completed through 18 months, 12/24 completed through 21 months).
Time frame: Every 3 months up to a total of 21 months
Population: We could only analyze patients who agreed to fill out the questionnaires.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Experimental Arm | Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Month 0 | 118 Score on a Scale |
| Experimental Arm | Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Month 3 | 112 Score on a Scale |
| Experimental Arm | Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Month 6 | 115 Score on a Scale |
| Experimental Arm | Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Month 9 | 119 Score on a Scale |
| Experimental Arm | Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Month 12 | 120 Score on a Scale |
| Experimental Arm | Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Month 15 | 120 Score on a Scale |
| Experimental Arm | Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Month 18 | 122 Score on a Scale |
| Experimental Arm | Patient Reported Outcomes as Assessed by Functional Assessment of Cancer Therapy - Prostate (FACT-P) Scale - Patient Questionnaire | Month 21 | 113 Score on a Scale |
Secondary
Prostate Cancer Specific Survival
Prostate cancer specific survival
Time frame: up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental Arm | Prostate Cancer Specific Survival | 100 percentage of participants |
Secondary
Time to Biochemical Progression
biochemical, radiographic, or clinical
Time frame: up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Arm | Time to Biochemical Progression | NA months |
Secondary
Time to Initiation of Additional Antineoplastic Therapy
antineoplastic therapy includes any systemic or focal anti-prostate cancer therapy
Time frame: up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Arm | Time to Initiation of Additional Antineoplastic Therapy | NA months |
Secondary
Time to Radiographic Progression
per PCWG3 criteria
Time frame: up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental Arm | Time to Radiographic Progression | NA months |