Clinical Trials /

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

NCT03572387

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: GCO 16-0752
  • NCT ID: NCT03572387

Conditions

  • Prostatic Neoplasms
  • Prostate Neoplasms
  • Prostate Cancer

Interventions

DrugSynonymsArms
5-Azacitidine5-AZA(5-AZA) + (ATRA) combination
all trans retinoic acidATRA(5-AZA) + (ATRA) combination
Lupron(5-AZA) + (ATRA) combination

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
(5-AZA) + (ATRA) combinationExperimentalCombination 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.
  • 5-Azacitidine
  • all trans retinoic acid
  • Lupron
Lupron onlyActive ComparatorNo treatment after one month of Lupron
  • Lupron

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Disease Progression-Free Rate
Time Frame:Baseline and 12 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Time to tumor progression
Time Frame:up to 24 months
Safety Issue:
Description:Time to tumor progression.
Measure:Measurement of TGFβ2 dormancy biomarker levels
Time Frame:up to 24 months
Safety Issue:
Description:The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
Measure:Measurement of BMP7 dormancy biomarker levels
Time Frame:up to 24 months
Safety Issue:
Description:The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
Measure:Measurement of BMP4 dormancy biomarker levels
Time Frame:up to 24 months
Safety Issue:
Description:The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
Measure:Measurement of GAS6 dormancy biomarker levels
Time Frame:up to 24 months
Safety Issue:
Description:The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
Measure:Measurement of retinoic acid dormancy biomarker levels
Time Frame:up to 24 months
Safety Issue:
Description:The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.
Measure:Measurement of NR2F1 dormancy biomarker levels
Time Frame:up to 24 months
Safety Issue:
Description:The measurement of dormancy biomarker levels in relation to disease states: tumor progression and disease progression.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Icahn School of Medicine at Mount Sinai

Trial Keywords

  • Prostate Neoplasms
  • Prostatic Neoplasms
  • 5-Azacitidine
  • all-trans retinoic acid
  • PSA

Last Updated

July 19, 2019