Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT01253642
First received: November 15, 2010
Last updated: June 16, 2015
Last verified: June 2015
  Purpose

This phase II trial studies how well giving phenelzine sulfate together with docetaxel works in treating patients with prostate cancer that is growing, spreading, or getting worse after first-line therapy with docetaxel. Phenelzine sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Phenelzine sulfate may also help docetaxel work better by making tumor cells more sensitive to the drug. Giving phenelzine sulfate together with docetaxel may kill more tumor cells.


Condition Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of MAOA Inhibitor Plus Docetaxel in Patients Receiving and Progressing on Docetaxel Therapy

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Proportion of patients who experience a PSA decline of at least 30% [ Time Frame: Within 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of progression free survival after initiation of combination phenelzine and docetaxel therapy [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.

  • Frequency of MAOA overexpression in CRPC tumors that are progressing on docetaxel [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Reported using descriptive statistics. A Pearson's correlation will be used to correlate tumor biopsy MAOA expression and circulating tumor cells MAOA expression.

  • HIF-1alpha expression in circulating tumor cells as a potential measure of MAO and activity [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • MAOA expression in circulating tumor cells and comparison to biopsy MAOA expression [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Reported using a waterfall plot.

  • Response rate in measurable disease by RECIST criteria [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Time to death from all causes [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Assessed using the Kaplan-Meier method.

  • Toxicity of the regimen [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
    The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be utilized for adverse event (AE) reporting.


Other Outcome Measures:
  • Frequency of gene expression [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Will be reported using descriptive statistics.

  • Frequency of LSD-1 expression [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Will be reported using descriptive statistics.


Estimated Enrollment: 30
Study Start Date: July 2010
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 ultrasonography (TRUS)-guided prostate biopsy OR image-guided (CT or ultrasound) core bone or soft tissue biopsy
Other Names:
  • Prostate Biopsy
  • Prostatic Biopsy
Drug: Docetaxel
Given IV
Other Names:
  • DOCETAXEL
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Phenelzine Sulfate
Given PO
Other Names:
  • Nardil
  • PHENELZINE SULFATE

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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/microliter (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01253642

Locations
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Tomasz M. Beer    503-494-0365    beert@ohsu.edu   
Principal Investigator: Tomasz M. Beer         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Peter S. Nelson    800-422-6237    pnelson@fhcrc.org   
Principal Investigator: Peter S. Nelson         
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Evan Y. Yu    800-804-8824    evanyu@u.washington.edu   
Principal Investigator: Evan Y. Yu         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Tomasz Beer OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT01253642     History of Changes
Other Study ID Numbers: IRB00005688, NCI-2010-02037, SOL-09105-LM, 5688, OHSU-5688, MR00045508, IRB00005688, P30CA069533
Study First Received: November 15, 2010
Last Updated: June 16, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Docetaxel
Phenelzine
Antidepressive Agents
Antimitotic Agents
Antineoplastic Agents
Central Nervous System Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Monoamine Oxidase Inhibitors
Pharmacologic Actions
Psychotropic Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on August 30, 2015