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

NCT01253642 | Terminated Phase 2 Results DMC

• 9 other identifiers: IRB00005688NCI-2010-02037SOL-09105-LM5688OHSU-5688e5688MR00045508MR46390P30CA069533
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Hormone-Resistant Prostate Cancer; Metastatic Prostatic Adenocarcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma

Outcome Measures

Primary Outcomes (1)

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

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

  Within 12 weeks

Secondary Outcomes (8)

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

  Up to 6 years

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

  Baseline

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

  Up to 6 years

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

  Up to 6 years

• Maximum Change in PSA

  12 weeks (or earlier in patients who discontinued early)

Study Arms (1)

Treatment (antiangiogenesis, chemosensitizer, chemotherapy)

EXPERIMENTAL

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; Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Drug: Phenelzine Sulfate

Interventions

Biopsy of Prostate PROCEDURE

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

Also known as: Prostate Biopsy, Prostatic Biopsy

Treatment (antiangiogenesis, chemosensitizer, chemotherapy)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (antiangiogenesis, chemosensitizer, chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (antiangiogenesis, chemosensitizer, chemotherapy)

Phenelzine Sulfate DRUG

Given PO

Also known as: Nardil

Treatment (antiangiogenesis, chemosensitizer, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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/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)

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• The Wayne D. Kuni and Joan E. Kuni Foundation: collaborator

Study Sites (3)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; Phenelzine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Hydrazines

Limitations and Caveats

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

Results Point of Contact

• Title: Kristi Eilers
• Organization: OHSU Knight Cancer Institute

eilersk@ohsu.edu

503-494-2897

Study Officials

• Tomasz Beer

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 15, 2010
• First Posted: December 3, 2010
• Study Start: July 12, 2010
• Primary Completion: September 15, 2016
• Study Completion: September 15, 2017
• Last Updated: October 2, 2019
• Results First Posted: December 11, 2017

Record last verified: 2019-09

Locations

US (3)