Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Newly Diagnosed Oligometastatic Prostate Cancer
• Intervention / Treatment: Procedure: radical prostatectomy; Radiation: stereotactic body radiotherapy; Drug: Leuprolide; Drug: apalutamide; Drug: abiraterone

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).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System, Long Beach, CA
    • West Los Angeles, California, United States, 90073-1003
      • VA Greater Los Angeles Healthcare System, West Los Angeles, CA
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center, Richmond, VA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Procedure: radical prostatectomy; surgical removal of the prostate; Radiation: stereotactic body radiotherapy; Highly targeted radiation; Other Names: SBRT; Drug: Leuprolide; Lowers serum testosterone; Other Names: ADT; Drug: apalutamide; antiandrogen; Other Names: ARN-509; Drug: abiraterone; Inhibits androgen synthesis; Other Names: zytiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 months after recovery of testosterone

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to biochemical progression	biochemical, radiographic, or clinical	up to 5 years
Time to radiographic progression	per PCWG3 criteria	up to 5 years
Time to initiation of additional antineoplastic therapy	antineoplastic therapy includes any systemic or focal anti-prostate cancer therapy	up to 5 years
Prostate cancer specific survival	Prostate cancer specific survival	up to 5 years
Patient reported outcomes as assedded 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 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.	up to 5 years
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).	up to 5 years

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Nicholas George Nickols, MD PhD, VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: September 26, 2017
• First Posted (Actual): September 29, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: SBRT; abiraterone; oligometastatic; apalutamide
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: ONCA-013-16F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No