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A Phase II Study of MAOA (Monoamine Oxidase A) Inhibitor Plus Docetaxel in Patients Currently Receiving and Progressing on Docetaxel Therapy

Phase 2
18 Years
Open (Enrolling)
Adenocarcinoma of the Prostate, Castrate Resistant Prostate Cancer, Recurrent Prostate Cancer

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Trial Information

A Phase II Study of MAOA (Monoamine Oxidase A) Inhibitor Plus Docetaxel in Patients Currently Receiving and Progressing on Docetaxel Therapy

PRIMARY OBJECTIVES: I. To determine the proportion of patients who experience a PSA
(Prostate Specific Antigen) decline of at least 30% within 12 weeks of initiation of therapy
when phenelzine 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 RECIST criteria. III. To report the maximum
change in PSA from baseline to 12 weeks (or earlier in patients who discontinue early) by
waterfall plot. IV. To determine the toxicity of the regimen in CRPC (Castrate Resistant
Prostate Cancer) previously treated with docetaxel. V. To determine time to death from all
causes. VI. To determine the frequency of MAOA overexpression in CRPC tumors that are
progressing on docetaxel. VII. To collect blood and tissue specimens for future molecular
correlative studies. VIII. To validate MAOA assessment in circulating tumor cells. IX. To
assess correlation with tissue expression of MAOA. X. To measure HIF-1alpha expression in
circulating tumor cells as a potential measure of MAO activity. OUTLINE: This is a
dose-escalation study of phenelzine sulfate. Patients receive oral phenelzine sulfate once
daily on days -7 to -4, and then twice daily 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. After completion of study
treatment, patients are followed up every 6 months.

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 a baseline tumor biopsy

- Evidence of castration resistant prostate cancer (CRPC) indicated by history of
progression despite standard hormonal therapy (by PSA and/or imaging studies)

- Prior therapy with at least four cycles of docetaxel with at least one PSA
measurement during docetaxel therapy that was lower than the pre-docetaxel baseline.
Combination therapy that includes docetaxel and non-cytoxic agents (biologic agents)
is allowable; prior treatment with weekly docetaxel is not allowable

- Evidence of early progression during (while on therapy or within 45 days of the last
dose administered) docetaxel therapy defined as:

- Increasing serum PSA level: Three increasing measurements obtained after exposure to
first-line docetaxel treatment are required; if the third PSA value is less than the
second, an additional fourth test to confirm a rising PSA is acceptable

- AND/OR progressive measurable disease: at least a 20% increase in the sum of the
longest diameters of measurable lesions over the smallest sum observed -or- the
appearance of one or more new lesions as assessed by CT scan after exposure to
first-line docetaxel treatment; measurable lesions include nodal lesions >= 20 mm in
diameter or visceral/soft-tissue lesions >= 10 mm in diameter

- AND/OR bone Scan Progression: appearance of 2 or more new lesions on bone scan after
exposure to first-line docetaxel treatment

- 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

- Evidence of MAOA expression (2 or higher) in metastasis biopsy specimen

- Serum testosterone levels < 50 ng/dL (unless surgically castrate); patients must
continue androgen deprivation with an LHRH agonist if they have not undergone

- ECOG performance status =< 2

- At least 15 days has passed since receiving the last dose of docetaxel at the time of
initiation of study drug

- 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

- Bilirubin =< 1.5 times ULN (if total bilirubin elevated, but direct is WNL, patient
is eligible)

- creatinine =< 1.5 times upper limit of normal (ULN)

- ALT =< 2.5 times ULN

- PSA > 2 ng/mL

- Life expectancy > 3 months

- Signed informed consent

- For patients who meet all of the above criteria, but have been off docetaxel therapy
for more than 6 weeks, current evidence of progression is also required

Exclusion Criteria:

- Received any other cytotoxic chemotherapy as a second-line treatment after first-line
docetaxel-based therapy

- 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

- Concurrent therapy: Excluded Concomitant medications: 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 methylclothiazide,
furazolidone, rasagiline, buspirone HCL; Serotoninergic Drugs: fluvoxamine (e.g.,
Luvox), fluoxetine (e.g., Prozac), paroxetine (e.g., Paxil), sertraline (e.g.,
Zoloft), dexfenfluramine, citoprolam, 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 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.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the proportion of patients who experience a PSA (Prostate Specific Antigen) decline of at least 30% within 12 weeks of therapy

Outcome Description:

To determine the proportion of patients who experience a PSA (Prostate Specific Antigen) decline of at least 30% within 12 weeks of initiation of therapy when phenelzine is added to docetaxel in patients who have evidence of progression on standard docetaxel.

Outcome Time Frame:

Within 12 weeks of initiation of therapy

Safety Issue:


Principal Investigator

Tomasz Beer

Investigator Role:

Principal Investigator

Investigator Affiliation:

OHSU Knight Cancer Institute


United States: Institutional Review Board

Study ID:




Start Date:

October 2010

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Castrate Resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



OHSU Knight Cancer Institute Portland, Oregon  97239