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A Pilot Study of 5-AZA and ATRA for Prostate Cancer With PSA-only Recurrence After Local Treatment

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: NCT03572387
Recruitment Status : Recruiting
First Posted : June 28, 2018
Last Update Posted : July 23, 2020
Sponsor:
Information provided by (Responsible Party):
William K. Oh, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE June 18, 2018
First Posted Date  ICMJE June 28, 2018
Last Update Posted Date July 23, 2020
Actual Study Start Date  ICMJE August 20, 2018
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 21, 2020)
  • Change in Disease Progression-Free Rate [ Time Frame: Baseline and 24 weeks ]
    The disease progression-free rate at the end of treatment period of 24 weeks. Disease progression is defined as a composite of PSA or radiographic progression relative to baseline, whichever occurs first.
  • Percentage of adverse events by grade [ Time Frame: 24 weeks ]
    Safety will be assessed by the recording of adverse events. Adverse events will be graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The percentage of patients for each observed adverse effect will be reported by grade.
Original Primary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
  • Change in Disease Progression-Free Rate [ Time Frame: Baseline and 12 weeks ]
    The disease progression-free rate at the end of treatment period of 12 weeks. Disease progression is defined as a composite of PSA or radiographic progression relative to baseline, whichever occurs first.
  • Percentage of adverse events by grade [ Time Frame: 12 weeks ]
    Safety will be assessed by the recording of adverse events. Adverse events will be graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The percentage of patients for each observed adverse effect will be reported by grade.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2020)
  • Prolongation of PSADT > 10 months at 24 weeks [ Time Frame: 24 weeks ]
    prostate-specific antigen doubling time
  • Measurement of TGFβ2 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of BMP7 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of BMP4 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of GAS6 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of retinoic acid dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of NR2F1 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
  • Time to tumor progression [ Time Frame: up to 24 months ]
    Time to tumor progression.
  • Measurement of TGFβ2 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of BMP7 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of BMP4 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of GAS6 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of retinoic acid dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
  • Measurement of NR2F1 dormancy biomarker levels [ Time Frame: up to 24 months ]
    The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pilot Study of 5-AZA and ATRA for Prostate Cancer With PSA-only Recurrence After Local Treatment
Official Title  ICMJE A Pilot Study of the Combination of 5-azacitidine (5-AZA) and All-trans Retinoic Acid (ATRA) for Prostate Cancer (PCa) With PSA-only Recurrence After Definitive Local Treatment
Brief Summary This is a prospective, open-label, randomized, cross-over, pilot study of reprogramming therapy in patients with recurrent PCa based on rising PSA only. The primary objectives are to compare the disease progression-free rate at the end of 12 weeks between 5-AZA+ATRA and no therapy and to assess safety of the 5-AZA and ATRA combination. All study enrollees will receive Lupron. After one month, they will be assigned in a 1:1 randomization to either the `5-AZA+ATRA' group or the `no therapy' group. Patients in the `5-AZA + ATRA' group will receive treatment on a 28-day cycle, in the absence of prohibitive toxicities, for 3 cycles. Patients will initially be observed for 3 cycles under either no therapy or combination therapy, before crossing over to receive the opposite treatment for another 3 cycles in the absence of prohibitive toxicities. After the treatment period, all patients will be followed for a total of 24 months from the start of the study or until the events leading to discontinuation are observed.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Subjects will be assigned in a 1:1 randomization to either the '5-AZA+ATRA' group or the 'no therapy' group. Patients in the '5-AZA + ATRA' group will receive treatment on a 28-day cycle, in the absence of prohibitive toxicities, for 3 cycles. Patients will initially be observed for 3 cycles under either no therapy or combination therapy, before crossing over to receive the opposite treatment for another 3 cycles in the absence of prohibitive toxicities.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostatic Neoplasms
  • Prostate Neoplasms
  • Prostate Cancer
Intervention  ICMJE
  • Drug: 5-Azacitidine
    subcutaneously on days 1-5 at a dose of 40 mg/m^2
    Other Name: 5-AZA
  • Drug: all trans retinoic acid
    45 mg/m^2, will be taken orally on days 3-7 of each cycle, divided into two doses
    Other Name: ATRA
  • Drug: Lupron
    7.5 mg x 1
Study Arms  ICMJE
  • Experimental: (5-AZA) + (ATRA) combination
    Combination of 5-Azacitidine (5-AZA) + all trans retinoic acid (ATRA) group after one month of Lupron, group will receive treatment on a 28-day cycle, in the absence of prohibitive toxicities, for 3 cycles.
    Interventions:
    • Drug: 5-Azacitidine
    • Drug: all trans retinoic acid
    • Drug: Lupron
  • Active Comparator: Lupron only
    No treatment after one month of Lupron
    Intervention: Drug: Lupron
Publications * Not Provided

*   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: June 26, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate
  • Rising PSA
  • PSADT ≤ 10 months prior to initiation of ADT
  • No evidence of regional or active distant metastases, except for regional metastasis where salvage radiation therapy is not an option
  • Indication for ADT after receiving definitive local therapy
  • Males ≥ 18 years.
  • ECOG performance status of ≤ 2
  • Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 90 days after completion of therapy
  • Ability to understand and the willingness to sign a written informed consent
  • Ability to adhere to the study visit schedule and requirements of the protocol

Exclusion Criteria:

  • Patients who have received ADT and/or other chemotherapy within 3 months prior to entering the study.
  • Patients who have had radiotherapy or surgery within 4 weeks prior to entering the study. Minimally-invasive procedures for the purpose of diagnosis or staging of the disease are permitted.
  • Patients may not be receiving any other investigational agents.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-AZA and ATRA.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Significant active cardiac disease within the previous 6 months
  • Inadequate organ and marrow function as defined below:
  • leukocytes ≤ 3,000/mcL
  • absolute neutrophil count ≤ 1,500/mcL
  • platelets ≤ 100,000/mcl
  • total bilirubin above normal institutional limits
  • AST(SGOT)/ALT(SPGT) ≥ 2.5 X institutional upper limit of normal
  • creatinine above normal institutional limits
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: William Oh, MD 212-659-5549 william.oh@mssm.edu
Contact: Kiev Gimpel-Tetra, MD 212-824-7117 kiev.gimpel-tetra@mssm.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03572387
Other Study ID Numbers  ICMJE GCO 16-0752
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
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data collected during the course of this clinical trial will primarily be shared with other investigators and health system staff, the IRB, FDA, and other reporting agencies, and/or transferred to other collaborators. Prior to transfer, the data collected must comply with, and must be limited by, the MSH's guidelines for Protecting the Rights and Privacy of Human Subjects.
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Time Frame: 24 months
Access Criteria: At the end of study completion. It will be available for 5 years.
Responsible Party William K. Oh, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: William Oh, MD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date July 2020

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