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

NCT03572387 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 16-0752
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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 of treatment 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. In the 'no therapy' group, patients will initially be observed for 3 cycles and then receive treatment for 3 cycles, in the absence of prohibitive toxicities. After the treatment period, all patients will be followed for up to 24 months from the start of the study or until the events leading to discontinuation are observed.

Conditions

Prostatic Neoplasms; Prostate Neoplasms; Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With PSA Response

  Number of participants with PSA response, as defined by PSA decreased \> 30% as compared from baseline.

  baseline and 24 weeks

Secondary Outcomes (1)

• Percentage of Patients With Prolongation of PSA Doubling Time (PSADT) Post-treatment

  baseline and 24 weeks

Study Arms (2)

5-AZA + ATRA ('early' 5-AZA+ATRA)

EXPERIMENTAL

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; Drug: all trans retinoic acid; Drug: Lupron

No therapy ('delayed' 5-AZA+ATRA)

ACTIVE COMPARATOR

After one month of lupron, patients will receive no therapy for 3 cycles (12 weeks). After this observation period, patients will receive combination of 5-Azacitidine (5-AZA) + all trans retinoic acid (ATRA) group on a 28-day cycle, in the absence of prohibitive toxicities, for 3 cycles.

Drug: 5-Azacitidine; Drug: all trans retinoic acid; Drug: Lupron

Interventions

5-Azacitidine DRUG

subcutaneously on days 1-5 at a dose of 40 mg/m\^2

Also known as: 5-AZA

5-AZA + ATRA ('early' 5-AZA+ATRA); No therapy ('delayed' 5-AZA+ATRA)

all trans retinoic acid DRUG

45 mg/m\^2, will be taken orally on days 3-7 of each cycle, divided into two doses

Also known as: ATRA

5-AZA + ATRA ('early' 5-AZA+ATRA); No therapy ('delayed' 5-AZA+ATRA)

Lupron DRUG

7.5 mg x 1

Also known as: Leuprolide

5-AZA + ATRA ('early' 5-AZA+ATRA); No therapy ('delayed' 5-AZA+ATRA)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Azacitidine; Tretinoin; Leuprolide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Vaibhav Patel, MD
• Organization: Icahn School of Medicine at Mount Sinai

vaibhav.patel@mountsinai.org

212-659-5511

Study Officials

• Vaibhav G Patel, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: ll 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 'delay 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. In the 'no therapy' group, patients will initially be observed for 3 cycles and then receive treatment for 3 cycles, in the absence of prohibitive toxicities. After the treatment period, all patients will be followed for up to 24 months from the start of the study or until the events leading to discontinuation are observed.

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: June 28, 2018
• Study Start: August 20, 2018
• Primary Completion: June 19, 2022
• Study Completion: July 8, 2022
• Last Updated: April 30, 2024
• Results First Posted: April 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 24 months
• Access Criteria: At the end of study completion. It will be available for 5 years.

Locations

US (1)