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Genital Diseases, Male

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Male Urogenital Diseases

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All Drugs and Chemicals

Psychotropic Drugs

Docetaxel

Phenelzine

Tubulin Modulators

Antimitotic Agents

Antidepressive Agents

Monoamine Oxidase Inhibitors

Enzyme Inhibitors

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.

Undergo transrectal ultrasound (TRUS) guided prostate biopsy OR image-guided (CT or ultrasound) core bone or soft tissue biopsy

Biopsy of Prostate

Laboratory Biomarker Analysis

Phenelzine Sulfate

Tomasz Beer

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.

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.

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

PSA response: A ≥ 30% reduction from baseline within 12 weeks of initiation of therapy (confirmed on a second measurement at least 3 weeks later).

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.

Reported as Number of participants with MAOA expression greater than 5%.

A Pearson's correlation will be used to correlate tumor biopsy MAOA expression and circulating tumor cells MAOA expression.

Measured from Day 1 of Combination therapy to PSA at 12 Weeks on therapy (or earlier if subject not on therapy for 12 weeks).

Response in measurable disease is defined as a 30% decrease in the sum of diameters of target lesions (as described by RECIST 1.1).

Time to death is calculated from Day 1 of Combination therapy to death from any cause.

Number of participants who experienced an Adverse Event. Detail of Adverse Events is reported in the Adverse Event Section

National Cancer Institute (NCI)

The Wayne D. Kuni and Joan E. Kuni Foundation

OHSU Knight Cancer Institute

Principal Investigator

Serious Adverse Events are considered Serious only if they are both unexpected and related to study. Hospitalizations that are expected for these study agents or the study population are not considered Serious Adverse Events.

Only Adverse Events that are considered possibly or definitely related to the study are reported.

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.

Combination Phenelzine and Docetaxel

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Early termination leading to small numbers of subjects analyzed; overall morbidity of patient population prohibited long term treatment or follow-up.

Kristi Eilers

Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30%

1 subject withdrew from the study before the first evidence of progression and is not included in this progression free survival analysis.

Duration of Progression Free Survival After Initiation of Combination Phenelzine and Docetaxel Therapy

Subjects who had evaluable samples collected immediately prior to initiation of Combination Therapy. 3 subjects did not have evaluable samples and were not included in this analysis.

Frequency of MAOA (Monoamine Oxidase A) Overexpression in CRPC (Castration-Resistant Prostate Cancer) Tumors That Are Progressing on Docetaxel

Of eleven subjects, CTC samples were collected from only 3. No testing was conducted on these 3 samples.

HIF-1alpha Expression in CTC (Circulating Tumor Cells) as a Potential Measure of MAO Activity

MAOA Expression in CTC (Circulating Tumor Cells) and Comparison to Biopsy MAOA Expression

1 subject withdrew from the study before reaching 12 weeks and is not included in this progression free survival analysis.

Maximum Change in PSA

3 subjects were excluded from this response rate calculation as they did not have additional scans beyond baseline.

Response Rate in Measurable Disease by RECIST (Response Evaluation Criteria In Solid Tumors) Criteria

Time to Death From All Causes

Toxicity of the Regimen

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Paclitaxel

Albumin-Bound Paclitaxel

There are five patient cohort groups. Each will receive a progressively higher starting dose of phenelzine sulfate, consecutively. Cohort A will start at 15mg/day and will be increased to 30mg/d by week 2 and further increased to 45mg/d for week 3, which will be maintained throughout the study. Cohort B will start at 45mg/d and will be held constant throughout the Study. Similarly, Cohort C, D \& E will start at 60, 75 and 90mg/d, respectively, and will also be held on this dose throughout the study. The decision to escalate the dose for the next cohort will be made on the basis of the number of dose limiting toxicity (DLT) events observed during the first 8 weeks in the preceding cohort group. In addition, all cohort groups will receive a constant dose of Abraxane at 100mg/m2.

Abraxane is administered intravenous at a constant dose of 100mg/m2

Nanoparticle albumin-bound paclitaxel

Nardil is administered orally from a starting dose of 15mg/d to a maximum of 90mg/d

Desmond Yip, MBBS

Laeeq Malik, MBBS

This phase 1b study will determine the safety and efficacy of combined treatment of Abraxane and phenelzine sulfate (Nardil) for metastatic or locally advanced breast cancer.

Participants may be eligible to join this study if they are aged 18 years or above and have been diagnosed with metastatic breast cancer or inoperable locally advanced breast cancer.

All participants will receive a combination of intravenous Abraxane and an oral dose of phenelzine sulfate. Abraxane will be administered weekly for the first 3 weeks of a 4-week cycle for 3 consecutive cycles. Phenelzine sulfate will be taken daily for the duration of the 3 cycles. Five patient cohort groups will receive a progressively increasing dose of phenelzine sulfate. Safety and efficacy will be assessed weekly over the 3 cycles of treatment.

Although both drugs have been used in clinical care for more than a decade, they have not been intentionally combined together in a cancer therapy setting. This means that the combined effect of these two drugs has not been documented. This is being addressed in this study.

Nanoparticle albumin-bound paclitaxel (Abraxane) will be administered intravenously over 3 cycles at a fixed dosage of 100mg/m2 to each study participant. This dose will be administered weekly for the first 3 consecutive weeks, over the 4 week cycle, before commencing the second and third cycles.

In addition to the fixed dose of nanoparticle albumin-bound paclitaxel, all patients will receive a continuous daily oral dose of phenelzine sulfate across all three cycles,

Each of the five patient cohort groups will receive a progressively higher starting dose of phenelzine sulfate, consecutively. Cohort A will start at 15mg/day and will be increased to 30mg/d by week 2 and further increased to 45mg/d for week 3, which will be maintained throughout the study. Cohort B will start at 45mg/d and will be held constant throughout the Study. Similarly, Cohort C, D \& E will start at 60, 75 and 90mg/d, respectively, and will also be held on this dose throughout the study. The decision to escalate the dose for the next cohort will be made on the basis of the number of dose limiting toxicity (DLT) events observed during the first 8 weeks in the preceding cohort group.

Phenelzine sulfate compliance will be monitored weekly based on drug tablet returns.

An open, non-randomised, cumulative cohort group design (across 5 groups) with a target toxicity fraction of 30% and a margin of 10%. This means that a dose will be escalated between groups when the observed toxicity rate is \< 20%, de-escalated when \> 40% and maintained otherwise.

The toxicity fraction is the number of participants receiving that dose who experience a DLT.

An Early Phase Study of Abraxane Combined With Phenelzine Sulfate in Patients With Metastatic or Advanced Breast Cancer

A Phase Ib Safety and Pharmacokinetics (PK)/ Pharmacodynamics (PD) Study to Determine the Dosage of Abraxane in Combination With Phenelzine Sulfate in Metastatic or Inoperable Locally Advanced Breast Cancer

It is the sponsors intention to publish the aggregated study results after the completion of the study.

The number of DLT events for nanoparticle albumin-bound paclitaxel and phenelzine sulfate combined, with the following events assessed using the NCI's CTCAE v4.3 toxicity criteria:

* Grade 3 Febrile neutropenia;
* Grade ≥2 peripheral neuropathy;
* Any Grade 3 non-haematological toxicity except alopecia; nausea, vomiting, or diarrhoea for 72 hrs due to inadequate use of prophylaxis;
* Grade 3 fatigue for \> 7 days;
* Non-hematologic Grade 3 or 4 laboratory AE that do not return to baseline or to Grade 1 within 7 days;
* Grade 3 thrombocytopenia with signs of significant bleeding or platelet count Grade 4;
* Blood bilirubin (total) Grade ≥3 for 72 hrs, AST or ALT Grade 3 for \>7 consecutive days, AST or ALT Grade 4;
* Persistent Grade 3 hypertension for \>7 days \& not responding to antihypertensive therapy or Grade 4 hypertension;
* An inability to administer treatment (with \>7 day delay) during Cycle 1 and Cycle 2 for toxicity reason; \&
* Any other treatment emergent SAE.

To assess maximum plasma concentration (ng/ml) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.

To assess the time after infusion of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate to achieve peak maximum plasma concentration (minutes).

To assess the terminal half-life (minutes) of nanoparticle albumin-bound paclitaxel alone and when combined with phenelzine sulfate.

To assess the area under nanoparticle albumin-bound paclitaxel concentration time curve from 0 to infinity (ng minutes / ml) and when combined with phenelzine sulfate.

To assess maximum plasma concentration (ng/ml) of phenelzine sulfate when combined with nanoparticle albumin-bound paclitaxel.

To assess the time after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel, to achieve peak maximum plasma concentration (minutes).

To assess the terminal half-life (minutes) after ingestion of phenelzine sulfate, when combined with nanoparticle albumin-bound paclitaxel.

To assess the area under Phenelzine Sulfate concentration time curve from 0 to infinity (ng minutes / ml) when combined with nanoparticle albumin-bound paclitaxel.

The CTC burden is expressed as the number of tumour cells observed per 30ml of blood.

The PDL1 expressing CTC burden is expressed as the number of CTC observed per 30ml of blood with PDL1 expression.

The HER2 expressing CTC burden is expressed as the number of CTC observed per 30ml of blood with PDL1 expression.

The number of tumour cells observed per FFPE slide.

The number of stoma cells observed per FFPE slide.

The number of CSC observed per FFPE slide.

The Canberra Hospital

Southern Medical Day Care Centre

Liverpool Cancer Therapy Centre

EpiAxis Therapeutics

Disease Attributes

Patients receive phenelzine sulfate 30 mg by mouth (PO) twice daily (BID) (starting dose of 15 mg daily escalated to 30 mg BID over 16 plus or minus 5 days). Patients who have been treated at 30 mg BID for over 3 cycles with resolution of any and all toxicities to grade \< or = 1 may increase the dose to a maximum of 45 mg BID at the discretion of the treating investigator. Treatment may continue in the absence of disease progression or unacceptable toxicity.

phenelzine sulfate

laboratory biomarker analysis

questionnaire administration

Mitchell Gross, MD

Jean C. Shih, PhD

This phase II trial studies phenelzine sulfate in treating patients with prostate cancer that has not spread to other parts of the body and has come back. Phenelzine sulfate is a type of antidepressant that works by decreasing the amount of a protein called monoamine oxidase (MAO). MAO drugs may have an anticancer effect in prostate cancer.

PRIMARY OBJECTIVES:

I. To assess the proportion of patients with biochemical recurrent prostate cancer (BCR-PC) treated with phenelzine (phenelzine sulfate) who achieve a prostate-specific antigen (PSA) decline of \>= 50% from baseline.

SECONDARY OBJECTIVES:

I. To monitor potential toxicities and/or beneficial effects on quality of life of phenelzine in prostate cancer patients.

II. To assess time to radiographic disease progression for patients with recurrent prostate cancer treated with phenelzine.

III. To collect blood and other samples to study the relationship between MAO activity and prostate cancer.

OUTLINE:

Patients receive phenelzine sulfate 30 mg by mouth (PO) twice daily (BID) (starting dose of 15 mg daily escalated to 30 mg BID over 16 plus or minus 5 days). Patients who have been treated at 30 mg BID for over 3 cycles with resolution of any and all toxicities to grade \< or = 1 may increase the dose to a maximum of 45 mg BID at the discretion of the treating investigator. Treatment may continue in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 3 years.

Phenelzine Sulfate in Treating Patients With Non-metastatic Recurrent Prostate Cancer

Phase 2 Trial of Phenelzine in Non-metastatic Recurrent Prostate Cancer

Assessed independently in two groups of patients defined according to circulating androgen levels as: non-castrate and castrate.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel	NCT01253642	Hormone-Resista... Metastatic Pros... Prostate Adenoc... Recurrent Prost...	Biopsy of Prost... Docetaxel Laboratory Biom... Phenelzine Sulf...	18 Years -	OHSU Knight Cancer Institute
An Early Phase Study of Abraxane Combined With Phenelzine Sulfate in Patients With Metastatic or Advanced Breast Cancer	NCT03505528	Metastatic Brea...	Nanoparticle al... Phenelzine Sulf...	18 Years -	EpiAxis Therapeutics
Phenelzine Sulfate in Treating Patients With Non-metastatic Recurrent Prostate Cancer	NCT02217709	Adenocarcinoma ... Recurrent Prost... Stage I Prostat... Stage IIA Prost... Stage IIB Prost... Stage III Prost...	phenelzine sulf... laboratory biom... questionnaire a...	18 Years -	University of Southern California
An Early Phase Study of Abraxane Combined With Phenelzine Sulfate in Patients With Metastatic or Advanced Breast Cancer	NCT03505528	Metastatic Brea...	Nanoparticle al... Phenelzine Sulf...	18 Years -	EpiAxis Therapeutics

Spots Global Cancer Trial Database for phenelzine sulfate