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

• Register: ClinicalTrials.gov
• Last refreshed on: 20 May 2013
• Main ID: NCT01253642
• Date of registration: 15/11/2010
• Primary sponsor: OHSU Knight Cancer Institute
• Public title: Phenelzine Sulfate and Docetaxel for Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel
• Scientific title: A Phase II Study of MAOA (Monoamine Oxidase A) Inhibitor Plus Docetaxel in Patients Currently Receiving and Progressing on Docetaxel Therapy
• Date of first enrolment: October 2010
• Target sample size: 20
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01253642
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Tim Newby

• Name: Tomasz Beer
• Affiliation: OHSU Knight Cancer Institute

Key inclusion & exclusion 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 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
orchiectomy

- 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)

- 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
MAOi

- 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

-


Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Adenocarcinoma of the Prostate

Castrate Resistant Prostate Cancer

Recurrent Prostate Cancer

Intervention(s)

Drug: docetaxel

Drug: phenelzine sulfate

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Procedure: prostate biopsy

Primary Outcome(s)

To determine the proportion of patients who experience a PSA (Prostate Specific Antigen) decline of at least 30% within 12 weeks of therapy [Time Frame: Within 12 weeks of initiation of therapy]

Secondary Outcome(s)

Frequency of MAOA (Monoamine Oxidase A) overexpression in CRPC(Castrate Resistant Prostate Cancer) tumors that are progressing on docetaxel [Time Frame: prior to initiation of study treatment]

HIF-1alpha expression in circulating tumor cells as a potential measure of MAO(Monoamine Oxidase) and activity [Time Frame: prior to study treatment, after 4 cycles of docetaxel, and at end of study treatment]

Measure MAOA (Monoamine Oxidase A) expression in circulating tumor cells and compare to biopsy MAOA expression. [Time Frame: Pre-study, after 4 cycles of docetaxel, and at the end of study treatment]

Report the maximum change in PSA (Prostate Specific Antigen) [Time Frame: From baseline to 12 weeks]

Response rate in measurable disease by RECIST (Response Evaluation Criteria In Solid Tumors) [Time Frame: Every 12 weeks after initiation of study therapy]

Time to death from all causes [Time Frame: measured from start of study therapy to time of death (approximately 12-24 months)]

To determine duration of progression free survival after initiation of combination phenelzine and docetaxel therapy [Time Frame: measured at time of progression by PSA (Prostate Specific Antigen), Measureable disease, or bone disease (approximately 6-24 months)]

To determine the toxicity of the regimen by documenting side effects related to the study treatment [Time Frame: every 3 weeks during study treatment]

Secondary ID(s)

IRB00005688

NCI-2010-02037

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)