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 July 2014 by OHSU Knight Cancer Institute
Sponsor:
Collaborators:
The Wayne D. Kuni and Joan E. Kuni Foundation
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT01253642
First received: November 15, 2010
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

This phase II trial is studying how well giving phenelzine sulfate together with docetaxel works in treating patients with prostate cancer with progressive disease 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
Adenocarcinoma of the Prostate
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Drug: docetaxel
Procedure: prostate biopsy
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 3 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier method will be used.

  • Response rate in measurable disease by RECIST criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Maximum change in PSA [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Reported using a waterfall plot.

  • Toxicity of the regimen [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    The descriptions and grading scales found in the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.

  • Time to death from all causes [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Assessed using the Kaplan-Meier method.

  • 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 3 years ] [ Designated as safety issue: No ]
  • MAOA expression in circulating tumor cells and comparison to biopsy MAOA expression [ Time Frame: Up to 3 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.


Estimated Enrollment: 30
Study Start Date: October 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.
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Procedure: prostate biopsy
Undergo transrectal ultrasound (TRUS)-guided prostate biopsy OR image-guided (CT or ultrasound) core bone or soft tissue biopsy
Other Names:
  • biopsy of prostate
  • prostatic biopsy
Other: laboratory biomarker analysis
Correlative studies
Drug: phenelzine sulfate
Given PO
Other Name: Nardil

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.

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.

  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 as not demonstrated evidence of progression for more than 45 days before enrollment ("late enrollees")
  • 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; excluded concomitant medications while on combination therapy: Sympathomimetic drugs or related compounds: Amphetamine, Dextroamphetamine, Benzphetamine, Dexmethylphenidate, Methamphetamine, phentermine, cocaine, methylphenidate, dopamine, epinephrine, norepinephrine, methyldopa, L-dopa (levodopa), L-tryptophan, L-tyrosine, Phenylalanine, Ephedrine, Isometheptene, Levonordefrin, Midodrine, meperidine (e.g., Demerol); other Monoamine oxidase (MAO) inhibitors: isocarboxazid (e.g., Marplan), procarbazine (e.g., Matulane), selegiline (e.g., Eldepryl), tranylcypromine (e.g., Parnate), pargyline hydrochloride, pargyline hydrochloride and methyclothiazide, furazolidone, rasagiline, buspirone hydrochloride (HCL); Serotoninergic Drugs: fluvoxamine (e.g., Luvox), fluoxetine (e.g., Prozac), paroxetine (e.g., Paxil), sertraline (e.g., Zoloft), dexfenfluramine, citalopram, venlafaxine, desvenlafaxine, duloxetine, escitalopram, milnacipran, Atomoxetine
  • Barbiturates, such as: Amobarbital, Butalbital, Pentobarbital, Phenobarbital, Secobarbital; Cough, Cold and Allergy products, such as: Dextromethorphan, Naphazoline, Oxymetazoline, Phenylephrine, Propylhexedrine, Pseudoephedrine; Tryptophan, Disulfiram, Entacapone, Reserpine, Sibutramine, Tolcapone, Bupropion HCL, guanethidine, serotonin receptor agonists (e.g. sumatriptan); Dibenzazepine Derivative Drugs: nortriptyline hydrochloride, amitriptyline hydrochloride, perphenazine and amitriptyline hydrochloride, clomipramine hydrochloride, desipramine hydrochloride, imipramine hydrochloride, doxepin, carbamazepine, cyclobenzaprine HCl, amoxapine, maprotiline HCl, trimipramine maleate, protriptyline HCl, mirtazapine
  • Other chemotherapeutic agents or biological response modifiers will be prohibited for the duration of the study
  • All herbal supplements will be prohibited
  • The following foods and beverages must be avoided: Meat and Fish: Pickled herring, Liver, Dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna); Vegetables: Broad bean pods (fava bean pods), Sauerkraut; Dairy Products: Cheese (particularly aged cheeses, cottage cheese and cream cheese are allowed), Yogurt; Beverages: Beer and wine, Alcohol-free and reduced-alcohol beer and wine products; Miscellaneous: Yeast extract (including brewer's yeast in large quantities), Meat extract, Excessive amounts of chocolate and caffeine
  • Systemic steroids, other than as premedication, will not be allowed on the study
  • While concurrent use of narcotic analgesics is not prohibited, phenelzine is known to interact with a variety of narcotic agents resulting in potential for greater central nervous system (CNS) depression, respiratory depression, and hypotension; 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 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, 98109-1023
Contact: Evan Y. Yu    800-804-8824    evanyu@u.washington.edu   
Principal Investigator: Evan Y. Yu         
Sponsors and Collaborators
OHSU Knight Cancer Institute
The Wayne D. Kuni and Joan E. Kuni Foundation
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, OHSU-5688, IRB00005688, P30CA069533
Study First Received: November 15, 2010
Last Updated: July 28, 2014
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on September 18, 2014