Clinical trial NCT03298087: Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer
Official title: Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Newly Diagnosed Oligometastatic Prostate Cancer
Keywords: oligometastatic
SBRT
abiraterone
apalutamide
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2017-09-29
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm Phase II clinical trial
Primary purpose: TREATMENT

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).

Eligibility criteria: 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)

Primary outcomes:
measure: PSA<0.05ng/mL (radical prostatectomy) or PSA <nadir+2ng/mL (prostate radiation)
timeFrame: 6 months after recovery of testosterone
Secondary outcomes:
measure: time to biochemical progression
timeFrame: up to 5 years
measure: Time to radiographic progression
timeFrame: up to 5 years
measure: Time to initiation of additional antineoplastic therapy
timeFrame: up to 5 years
measure: Prostate cancer specific survival
timeFrame: up to 5 years
measure: Patient reported outcomes as assedded by Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire
timeFrame: up to 5 years
measure: Number of participants with treatment-related adverse events as assessed by physician using CTCAE v4.0 criteria
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: VA Long Beach Healthcare System, Long Beach, CA
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
state: California
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center, Richmond, VA
state: Virginia
Study officials:
affiliation: VA Greater Los Angeles Healthcare System, West Los Angeles, CA
name: Nicholas George Nickols, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parikh NR, Huiza C, Patel JS, Tsai S, Kalpage N, Thein M, Pitcher S, Lee SP, Inouye WS, Jordan ML, Sanati H, Jafari L, Bennett CJ, Gin GE, Kishan AU, Reiter RE, Lewis M, Sadeghi A, Aronson WJ, Garraway IP, Rettig MB, Nickols NG. Systemic and tumor-directed therapy for oligometastatic prostate cancer: study protocol for a phase II trial for veterans with de novo oligometastatic disease. BMC Cancer. 2019 Apr 1;19(1):291. doi: 10.1186/s12885-019-5496-5.