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Trial record 6 of 6 for:    BMP4

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

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ClinicalTrials.gov Identifier: NCT03572387
Recruitment Status : Recruiting
First Posted : June 28, 2018
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
William K. Oh, Icahn School of Medicine at Mount Sinai

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.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Prostate Neoplasms Prostate Cancer Drug: 5-Azacitidine Drug: all trans retinoic acid Drug: Lupron Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
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
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
Actual Study Start Date : August 20, 2018
Estimated Primary Completion Date : February 28, 2021
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
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.
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

Active Comparator: Lupron only
No treatment after one month of Lupron
Drug: Lupron
7.5 mg x 1




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Time to tumor progression [ Time Frame: up to 24 months ]
    Time to tumor progression.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

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): NCT03572387


Contacts
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Contact: William Oh, MD 212-659-5549 william.oh@mssm.edu
Contact: Kiev Gimpel-Tetra, MD 212-824-7117 kiev.gimpel-tetra@mssm.edu

Locations
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United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Principal Investigator: William Oh, MD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Investigators
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Principal Investigator: William Oh, MD Icahn School of Medicine at Mount Sinai

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Responsible Party: William K. Oh, Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT03572387     History of Changes
Other Study ID Numbers: GCO 16-0752
First Posted: June 28, 2018    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (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
Informed Consent Form (ICF)
Time Frame: 24 months
Access Criteria: At the end of study completion. It will be available for 5 years.

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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
Keywords provided by William K. Oh, Icahn School of Medicine at Mount Sinai:
Prostate Neoplasms
Prostatic Neoplasms
5-Azacitidine
all-trans retinoic acid
PSA
Additional relevant MeSH terms:
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Prostatic Neoplasms
Recurrence
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Disease Attributes
Pathologic Processes
Azacitidine
Tretinoin
Leuprolide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Keratolytic Agents
Dermatologic Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal