Prostatic Neoplasms, Prostate Neoplasms, Prostate Cancer
Conditions
Keywords
Prostate Neoplasms, Prostatic Neoplasms, 5-Azacitidine, all-trans retinoic acid, PSA
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.
Interventions
DRUG5-Azacitidine
subcutaneously on days 1-5 at a dose of 40 mg/m\^2
45 mg/m\^2, will be taken orally on days 3-7 of each cycle, divided into two doses
DRUGLupron
7.5 mg x 1
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With PSA Response | baseline and 24 weeks | Number of participants with PSA response, as defined by PSA decreased \> 30% as compared from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Prolongation of PSA Doubling Time (PSADT) Post-treatment | baseline and 24 weeks | Percentage of patients with prolongation of PSA doubling time (PSADT) post-treatment compared to baseline after treatment with 3 cycles of Aza and ATRA. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 'Early' 5-AZA+ATRA Patients will receive Lupron 7.5 mg x 1. Four weeks later, they will receive treatment on a 28-day cycle, in the absence of toxicities, for 3 cycles.
Treatment:
5-Azacitidine: subcutaneously on days 1-5 at a dose of 40 mg/m\^2 all trans retinoic acid: 45 mg/m\^2, will be taken orally on days 3-7 of each cycle, divided into two doses
-Taken for 3 cycles | 6 |
| 'Delayed' 5-AZA+ATRA Patients will receive Lupron 7.5 mg x 1. Four weeks later, they will undergo observation every 28 days for 3 cycles. Thereafter, patients will receive 5-AZA+ATRA treatment on a 28-day cycle, in the absence of toxicities, for 3 cycles.
Treatment:
5-Azacitidine: subcutaneously on days 1-5 at a dose of 40 mg/m\^2 all trans retinoic acid: 45 mg/m\^2, will be taken orally on days 3-7 of each cycle, divided into two doses
-Taken for 3 cycles | 8 |
| Total | 14 |
Baseline characteristics
| Characteristic | Total | 'Early' 5-AZA+ATRA | 'Delayed' 5-AZA+ATRA |
|---|---|---|---|
| Age, Continuous | 66.4 years STANDARD_DEVIATION 7.64 | 62.3 years STANDARD_DEVIATION 6.8 | 71.8 years STANDARD_DEVIATION 5.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 5 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants |
| Gleason score <=7 (low to intermediate grade cancer) | 5 Participants | 0 Participants | 5 Participants |
| Gleason score >=8 (high grade cancer) | 8 Participants | 5 Participants | 3 Participants |
| Gleason score Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Prostate-Specific Antigen (PSA) doubling time | 2.89 months STANDARD_DEVIATION 1.33 | 3.51 months STANDARD_DEVIATION 1.48 | 2.43 months STANDARD_DEVIATION 1.06 |
| PSA | 4.75 ng/ml STANDARD_DEVIATION 7.81 | 7.11 ng/ml STANDARD_DEVIATION 11.7 | 2.99 ng/ml STANDARD_DEVIATION 2.56 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 5 / 6 | 8 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 |
Outcome results
Primary
Number of Participants With PSA Response
Number of participants with PSA response, as defined by PSA decreased \> 30% as compared from baseline.
Time frame: baseline and 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 'Early' 5-AZA+ATRA | Number of Participants With PSA Response | 0 Participants |
| 'Delayed' 5-AZA+ATRA | Number of Participants With PSA Response | 0 Participants |
Secondary
Percentage of Patients With Prolongation of PSA Doubling Time (PSADT) Post-treatment
Percentage of patients with prolongation of PSA doubling time (PSADT) post-treatment compared to baseline after treatment with 3 cycles of Aza and ATRA.
Time frame: baseline and 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 'Early' 5-AZA+ATRA | Percentage of Patients With Prolongation of PSA Doubling Time (PSADT) Post-treatment | 33.3 percentage of participants |
| 'Delayed' 5-AZA+ATRA | Percentage of Patients With Prolongation of PSA Doubling Time (PSADT) Post-treatment | 25 percentage of participants |