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

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

Tracking Information

• First Submitted Date: June 18, 2018
• First Posted Date: June 28, 2018
• Last Update Posted Date: July 23, 2020
• Actual Study Start Date: August 20, 2018
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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 (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: A Pilot Study of 5-AZA and ATRA for Prostate Cancer With PSA-only Recurrence After Local Treatment
• Official Title: 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: Interventional
• Study Phase: Phase 2

Study Design

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

• Prostatic Neoplasms
• Prostate Neoplasms
• Prostate Cancer

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 26, 2018): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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: United States

Administrative Information

• NCT Number: NCT03572387
• Other Study ID Numbers: 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

• 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: Icahn School of Medicine at Mount Sinai
• Collaborators: Not Provided

Investigators

• 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