Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel
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|ClinicalTrials.gov Identifier: NCT01253642|
Recruitment Status : Terminated (low enrollment)
First Posted : December 3, 2010
Results First Posted : December 11, 2017
Last Update Posted : December 11, 2017
|Condition or disease||Intervention/treatment||Phase|
|Hormone-Resistant Prostate Cancer Metastatic Prostatic Adenocarcinoma Prostate Adenocarcinoma Recurrent Prostate Carcinoma||Procedure: Biopsy of Prostate Drug: Docetaxel Other: Laboratory Biomarker Analysis Drug: Phenelzine Sulfate||Phase 2|
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I. To determine the proportion of patients who experience a prostate specific antigen (PSA) decline of at least 30% within 12 weeks of initiation of combination therapy when phenelzine (phenelzine sulfate) is added to docetaxel in patients who have evidence of progression on standard docetaxel.
I. To determine duration of progression free survival after initiation of combination phenelzine and docetaxel therapy.
II. To determine the response rate in measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after initiation of combination phenelzine and docetaxel therapy.
III. To report the maximum change in PSA from baseline to 12 weeks (or earlier in patients who discontinue early) by waterfall plot after initiation of combination phenelzine and docetaxel therapy.
IV. To determine the toxicity of the combination regimen in castration-resistant prostate cancer (CRPC) previously treated with docetaxel.
V. To determine time to death from all causes. VI. To determine the frequency of monoamine oxidase A (MAOA) overexpression in CRPC tumors that are progressing on docetaxel.
VII. To compare the level of MAOA expression in primary diagnostic tissue (e.g. biopsy or radical prostatectomy) with CRPC tumors that are progressing on docetaxel.
VIII. To correlate MAOA overexpression in CRPC tumors with response to combination study treatment.
IX. To collect blood and tissue specimens for future molecular correlative studies.
X. To validate MAOA assessment in circulating tumor cells. XI. To assess correlation with tissue expression of MAOA. XII. To measure hypoxia-inducible factor (HIF)-1alpha expression and other potential biomarkers in circulating tumor cells as a potential measure of MAO activity.
I. To measure expression of lysine-specific histone demethylase 1 (LSD1) in CRPC tumors that are progressing on docetaxel and correlate with the endpoints described in the primary objective and secondary objectives I, II, III, and V.
II. To conduct gene expression studies in CRPC tumors that are progressing on docetaxel and correlate them with and correlate with the endpoints described in the primary objective and secondary objectives I, II, III and V.
OUTLINE: This is a dose-escalation study of phenelzine sulfate.
Patients receive phenelzine sulfate orally (PO) once daily (QD) on days -7 to -4, and then twice daily (BID) on days -3 to 21. Patients receive docetaxel intravenously (IV) over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of MAOA Inhibitor Plus Docetaxel in Patients Receiving and Progressing on Docetaxel Therapy|
|Study Start Date :||July 12, 2010|
|Actual Primary Completion Date :||September 15, 2016|
|Actual Study Completion Date :||September 15, 2017|
Experimental: Treatment (antiangiogenesis, chemosensitizer, chemotherapy)
Patients receive phenelzine sulfate PO QD on days -7 to -4, and then BID on days -3 to 21. Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity.
Procedure: Biopsy of Prostate
Undergo transrectal ultrasound (TRUS) guided prostate biopsy OR image-guided (CT or ultrasound) core bone or soft tissue biopsy
Other: Laboratory Biomarker Analysis
Drug: Phenelzine Sulfate
Other Name: Nardil
- Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30% [ Time Frame: Within 12 weeks ]PSA response: A ≥ 30% reduction from baseline within 12 weeks of initiation of therapy (confirmed on a second measurement at least 3 weeks later).
- Duration of Progression Free Survival After Initiation of Combination Phenelzine and Docetaxel Therapy [ Time Frame: Up to 6 years ]Progression free survival is calculated as the time from Day 1 of Combination therapy to first evidence of progression (by PSA, Measureable Disease, or Clinical Progression). For subjects who did not meet progression criteria, date of new therapy or date of death was used. Outcome is reported as mean.
- Frequency of MAOA (Monoamine Oxidase A) Overexpression in CRPC (Castration-Resistant Prostate Cancer) Tumors That Are Progressing on Docetaxel [ Time Frame: Baseline ]Reported as Number of participants with MAOA expression greater than 5%.
- HIF-1alpha Expression in CTC (Circulating Tumor Cells) as a Potential Measure of MAO Activity [ Time Frame: Up to 6 years ]
- MAOA Expression in CTC (Circulating Tumor Cells) and Comparison to Biopsy MAOA Expression [ Time Frame: Up to 6 years ]A Pearson's correlation will be used to correlate tumor biopsy MAOA expression and circulating tumor cells MAOA expression.
- Maximum Change in PSA [ Time Frame: 12 weeks (or earlier in patients who discontinued early) ]Measured from Day 1 of Combination therapy to PSA at 12 Weeks on therapy (or earlier if subject not on therapy for 12 weeks).
- Response Rate in Measurable Disease by RECIST (Response Evaluation Criteria In Solid Tumors) Criteria [ Time Frame: Up to 6 years ]Response in measurable disease is defined as a 30% decrease in the sum of diameters of target lesions (as described by RECIST 1.1).
- Time to Death From All Causes [ Time Frame: Up to 6 years ]Time to death is calculated from Day 1 of Combination therapy to death from any cause.
- Toxicity of the Regimen [ Time Frame: Up to 6 years ]Number of participants who experienced an Adverse Event. Detail of Adverse Events is reported in the Adverse Event Section
- Frequency of Gene Expression [ Time Frame: Up to 6 years ]Outcome measure will be reported using descriptive statistics, after overall study completion (March 2019).
- Frequency of LSD-1 (Lysine-specific Histone Demethylase 1) Expression [ Time Frame: Up to 6 years ]Outcome measure will be reported using descriptive statistics, after overall study completion (March 2019).
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): NCT01253642
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Tomasz Beer||OHSU Knight Cancer Institute|