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Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03298087
Recruitment Status : Recruiting
First Posted : September 29, 2017
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Tracking Information
First Submitted Date  ICMJE September 26, 2017
First Posted Date  ICMJE September 29, 2017
Last Update Posted Date April 1, 2021
Actual Study Start Date  ICMJE July 1, 2018
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
PSA<0.05ng/mL [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
  • time to biochemical progression [ Time Frame: up to 5 years ]
    biochemical, radiographic, or clinical
  • Time to radiographic progression [ Time Frame: up to 5 years ]
    per PCWG3 criteria
  • Time to initiation of additional antineoplastic therapy [ Time Frame: up to 5 years ]
    antineoplastic therapy includes any systemic or focal anti-prostate cancer therapy
  • Prostate cancer specific survival [ Time Frame: up to 5 years ]
    Prostate cancer specific survival
  • Patient reported outcomes as assedded by Functional Assessment of Cancer Therapy - Prostate (FACT-P) scale - patient questionnaire [ Time Frame: up to 5 years ]
    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.
  • Number of participants with treatment-related adverse events as assessed by physician using CTCAE v4.0 criteria [ Time Frame: 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).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer
Official Title  ICMJE Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer
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), 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), 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Single arm Phase II clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Newly Diagnosed Oligometastatic Prostate Cancer
Intervention  ICMJE
  • Procedure: radical prostatectomy
    surgical removal of the prostate
  • Radiation: stereotactic body radiotherapy
    Highly targeted radiation
    Other Name: SBRT
  • Drug: Leuprolide
    Lowers serum testosterone
    Other Name: ADT
  • Drug: apalutamide
    antiandrogen
    Other Name: ARN-509
  • Drug: abiraterone
    Inhibits androgen synthesis
    Other Name: zytiga
Study Arms  ICMJE 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.
Interventions:
  • Procedure: radical prostatectomy
  • Radiation: stereotactic body radiotherapy
  • Drug: Leuprolide
  • Drug: apalutamide
  • Drug: abiraterone
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 26, 2017)
28
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2023
Estimated Primary Completion Date September 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Prostate cancer only affects males.
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nicholas G Nickols, MD PhD (310) 478-3711 nicholas.nickols@va.gov
Contact: Matthew B Rettig, MD (310) 478-3711 matthew.rettig@va.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03298087
Other Study ID Numbers  ICMJE ONCA-013-16F
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party VA Office of Research and Development
Study Sponsor  ICMJE VA Office of Research and Development
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nicholas George Nickols, MD PhD VA Greater Los Angeles Healthcare System, West Los Angeles, CA
PRS Account VA Office of Research and Development
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP