Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03298087
Recruitment Status : Recruiting
First Posted : September 29, 2017
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

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.

Condition or disease Intervention/treatment Phase
Newly Diagnosed Oligometastatic Prostate Cancer Procedure: radical prostatectomy Radiation: stereotactic body radiotherapy Drug: Leuprolide Drug: apalutamide Drug: abiraterone Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm Phase II clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Systemic and Tumor-Directed Therapy for Oligometastatic Prostate Cancer
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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 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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. time to biochemical progression [ Time Frame: up to 5 years ]
    biochemical, radiographic, or clinical

  2. Time to radiographic progression [ Time Frame: up to 5 years ]
    per PCWG3 criteria

  3. Time to initiation of additional antineoplastic therapy [ Time Frame: up to 5 years ]
    antineoplastic therapy includes any systemic or focal anti-prostate cancer therapy

  4. Prostate cancer specific survival [ Time Frame: up to 5 years ]
    Prostate cancer specific survival

  5. 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.

  6. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Prostate cancer only affects males.
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03298087


Contacts
Layout table for location contacts
Contact: Nicholas G Nickols, MD PhD (310) 478-3711 nicholas.nickols@va.gov
Contact: Matthew Rettig, MD (310) 478-3711 matthew.rettig@va.gov

Locations
Layout table for location information
United States, California
VA Long Beach Healthcare System, Long Beach, CA Recruiting
Long Beach, California, United States, 90822
Contact: May Thein    562-826-8000 ext 5755    May.Thein@va.gov   
Contact: May Thein    5628268000 ext 5755    May.Thein@va.gov   
VA Greater Los Angeles Healthcare System, West Los Angeles, CA Recruiting
West Los Angeles, California, United States, 90073
Contact: Nicholas G Nickols, MD PhD    (310) 478-3711    nicholas.nickols@va.gov   
Contact: Matthew Rettig, MD    (310) 478-3711    matthew.rettig@va.gov   
Principal Investigator: Nicholas George Nickols, MD PhD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Layout table for investigator information
Principal Investigator: Nicholas George Nickols, MD PhD VA Greater Los Angeles Healthcare System, West Los Angeles, CA

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03298087     History of Changes
Other Study ID Numbers: ONCA-013-16F
First Posted: September 29, 2017    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by VA Office of Research and Development:
oligometastatic
SBRT
abiraterone
apalutamide

Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Leuprolide
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents