A Phase II Study of MAOA Inhibitor Plus Docetaxel in Patients Receiving and Progressing on Docetaxel Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 3
- 主要终点
- Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30%
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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)
- •Life expectancy > 3 months
- •Signed informed consent
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Biopsy of Prostate (Procedure)
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.
干预措施: Docetaxel (Drug)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Phenelzine Sulfate (Drug)
结局指标
主要结局
Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30%
时间窗: Within 12 weeks
PSA response: A ≥ 30% reduction from baseline within 12 weeks of initiation of therapy (confirmed on a second measurement at least 3 weeks later).
次要结局
- Duration of Progression Free Survival After Initiation of Combination Phenelzine and Docetaxel Therapy(Up to 6 years)
- HIF-1alpha Expression in CTC (Circulating Tumor Cells) as a Potential Measure of MAO Activity(Up to 6 years)
- Response Rate in Measurable Disease by RECIST (Response Evaluation Criteria In Solid Tumors) Criteria(Up to 6 years)
- Time to Death From All Causes(Up to 6 years)
- Frequency of MAOA (Monoamine Oxidase A) Overexpression in CRPC (Castration-Resistant Prostate Cancer) Tumors That Are Progressing on Docetaxel(Baseline)
- 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))
- Toxicity of the Regimen(Up to 6 years)
研究者
Tom Beer
Principal Investigator
OHSU Knight Cancer Institute