- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01253642
Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel
A Phase II Study of MAOA Inhibitor Plus Docetaxel in Patients Receiving and Progressing on Docetaxel Therapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
TERTIARY OUTCOMES:
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Oregon
-
Portland, Oregon, United States, 97239
- OHSU Knight Cancer Institute
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center
-
Seattle, Washington, United States, 98109
- Seattle Cancer Care Alliance
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histological or cytological diagnosis of adenocarcinoma of the prostate
- Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
- Willingness to undergo tumor biopsy
- Evidence of CRPC indicated by history of progression despite standard hormonal therapy (by PSA and/or imaging studies)
- Planned or recent initiation of standard docetaxel therapy; patients may be enrolled after receiving standard docetaxel therapy as long as the patient has not demonstrated evidence of progression for more than 45 days before enrollment ("late enrollers")
- For patients who have been on anti-androgen therapy and had evidence of response to the addition of an anti-androgen (i.e., PSA reduction), patients must have discontinued anti-androgen therapy for at least six weeks (4 weeks for flutamide) without current evidence of an anti-androgen withdrawal response
- Serum testosterone levels < 50 ng/dL (unless surgically castrate); patients must continue androgen deprivation with an luteinizing hormone releasing hormone (LHRH) agonist if they have not undergone orchiectomy
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Has recovered from all therapy-related toxicity to =< grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy)
- Absolute neutrophil count >= 1500/uL
- Platelets >= 100,000
- Creatinine =< 1.5 times upper limit of normal (ULN)
- Bilirubin =< 1.5 times ULN (if total bilirubin elevated, but direct is within normal limits [WNL], patient is eligible)
- Alanine aminotransferase (ALT) =< 2.5 times ULN
- PSA > 2 ng/mL (at the time of enrollment or prior to initiation of docetaxel)
- Life expectancy > 3 months
- Signed informed consent
Exclusion Criteria:
- Significant peripheral neuropathy defined as grade 2 or higher
- A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm
- Significant active concurrent medical illness or infection precluding protocol treatment or survival
- Current uncontrolled hyperthyroidism
- Pheochromocytoma
- Carcinoid Syndrome
- Known or suspected brain metastases
- Treatment with radiotherapy within the past 4 weeks or radiopharmaceutical therapy (strontium, samarium) within the past 8 weeks
- Concurrent therapy with a Selective Serotonin Reuptake Inhibitor (SSRI), tricyclic antidepressant, or Monoamine Oxidase Inhibitor (MAOi); clinical judgment should be used in a decision to discontinue antidepressants; a minimum of a 1 week washout period is required for any tricyclic or related antidepressant, or any SSRI (2 weeks for paroxetine or sertraline, 5 weeks for fluoxetine); minimum 2 week washout for any MAOi
- Concurrent therapy with any excluded medications that cannot be safely discontinued prior to initiation of combination therapy; discontinuation prior to enrollment is not required, but discontinuation prior to combination therapy must be possible
- Caution should be exercised in patients who are regularly taking narcotic analgesics, particularly higher doses; the doses of narcotic analgesics may need to be reduced, patients may need to be monitored closely for drug interactions, and the risks and benefits of participation in the study should be considered; clinical judgment should be exercised to manage this potential drug interaction
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Correlative studies
Given IV
Other Names:
Undergo transrectal ultrasound (TRUS) guided prostate biopsy OR image-guided (CT or ultrasound) core bone or soft tissue biopsy
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
Within 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 6 years
|
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%.
|
Baseline
|
HIF-1alpha Expression in CTC (Circulating Tumor Cells) as a Potential Measure of MAO Activity
Time Frame: Up to 6 years
|
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.
|
Up to 6 years
|
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).
|
12 weeks (or earlier in patients who discontinued early)
|
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).
|
Up to 6 years
|
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.
|
Up to 6 years
|
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
|
Up to 6 years
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Adenocarcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Psychotropic Drugs
- Antidepressive Agents
- Monoamine Oxidase Inhibitors
- Docetaxel
- Phenelzine
Other Study ID Numbers
- IRB00005688 (OTHER: OHSU Knight Cancer Institute)
- P30CA069533 (U.S. NIH Grant/Contract)
- NCI-2010-02037 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- SOL-09105-LM
- 5688
- OHSU-5688
- e5688
- MR00045508
- MR46390
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prostate Adenocarcinoma
-
Case Comprehensive Cancer CenterTerminatedAdenocarcinoma of Prostate | Adenocarcinoma of the Prostate Stage I | Adenocarcinoma of the Prostate Stage II | Adenocarcinoma of the Prostate Stage IIIUnited States
-
NRG OncologyNational Cancer Institute (NCI)Active, not recruitingStage II Prostate Adenocarcinoma | Stage III Prostate Adenocarcinoma | Stage I Prostate AdenocarcinomaUnited States, Canada, Puerto Rico
-
Dana-Farber Cancer InstituteCompletedProstate Cancer | Adenocarcinoma of the Prostate Stage I | Adenocarcinoma of the Prostate Stage II | Adenocarcinoma of the Prostate Stage IIIUnited States
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)CompletedStage II Prostate Adenocarcinoma | Stage III Prostate Adenocarcinoma | Stage I Prostate AdenocarcinomaUnited States
-
University of California, San FranciscoCompletedProstate Adenocarcinoma | Recurrent Prostate Carcinoma | Stage III Prostate Adenocarcinoma AJCC v7 | Stage I Prostate Adenocarcinoma AJCC v7 | Stage II Prostate Adenocarcinoma AJCC v7United States
-
National Cancer Institute (NCI)Active, not recruitingCastration-Resistant Prostate Carcinoma | Metastatic Prostate Carcinoma | Stage IV Prostate Adenocarcinoma AJCC v7 | Advanced Prostate Adenocarcinoma With Neuroendocrine Differentiation | Metastatic Prostate Adenocarcinoma With Neuroendocrine Differentiation | Prostate Adenocarcinoma With Neuroendocrine...United States
-
Mayo ClinicNational Cancer Institute (NCI)WithdrawnStage II Prostate Adenocarcinoma | Stage I Prostate Adenocarcinoma
-
NRG OncologyNational Cancer Institute (NCI)Active, not recruitingProstate Adenocarcinoma | Stage II Prostate Adenocarcinoma | Stage III Prostate Adenocarcinoma | Stage I Prostate AdenocarcinomaUnited States, Canada, Switzerland
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage III Prostate Adenocarcinoma AJCC v7 | Stage II Prostate Adenocarcinoma AJCC v7 | Stage I Prostate Adenocarcinoma American Joint Committee on Cancer (AJCC) v7United States
-
Andrei IagaruCompletedStage II Prostate Adenocarcinoma | Stage III Prostate Adenocarcinoma | Stage IV Prostate AdenocarcinomaUnited States
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States