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Bicalutamide and Raloxifene Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

Phase 2
Withdrawn
Conditions
Stage I Prostate Adenocarcinoma
Stage II Prostate Adenocarcinoma
Interventions
Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration
Registration Number
NCT03147196
Lead Sponsor
Mayo Clinic
Brief Summary

This phase II pilot trial studies how well bicalutamide and raloxifene hydrochloride work in treating patients with prostate cancer undergoing surgery. Antihormone therapy, such as bicalutamide and raloxifene hydrochloride, may lessen the amount of androgens made by the body.

Detailed Description

PRIMARY OBJECTIVES:

I. To collect and interrogate samples in patients with prostate cancer that were diagnosed with prostate cancer and are planned for radical prostatectomy at Mayo Clinic Arizona.

SECONDARY OBJECTIVES:

I. To describe the adverse event profile and tolerance of therapy for 60 days of treatment prior to surgery.

II. To assess change in stage and/or grade of cancer and prostate specific antigen (PSA) response to neoadjuvant treatment in patients with hormone sensitive prostate cancer.

TERTIARY OBJECTIVES:

I. To evaluate specific pathways and changes when comparing biopsy specimens to prostatectomy.

II. To describe the quality of life of patients receiving hormonal therapy prior to radical prostatectomy.

OUTLINE: This is a dose-escalation study. Patients are randomized to 1 of 4 arms.

ARM A: Patients receive low dose raloxifene hydrochloride orally (PO) daily on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive low dose bicalutamide PO daily on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive low dose raloxifene hydrochloride PO daily and low dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

ARM D: Patients receive high dose raloxifene hydrochloride PO daily and high dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

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

Recruitment & Eligibility

Status
WITHDRAWN
Sex
Male
Target Recruitment
Not specified
Inclusion Criteria
  • Histological confirmation of adenocarcinoma of the prostate, >= Gleason 6, clinical stage T1a-T2c and planned for radical prostatectomy
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
  • Platelet count >= 50,000/mm^3
  • Hemoglobin > 9.0 g/dL
  • Creatinine =< 2.0 mg/dL
  • Provide informed written consent
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study); Note: during the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Patients must also provide written consent for biospecimens collection on Institutional Review Board (IRB) 08-000980
Exclusion Criteria
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • History of a venous thromboembolic event, cerebrovascular accident (CVA), hepatic impairment, or heart failure

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm A (raloxifene hydrochloride)Laboratory Biomarker AnalysisPatients receive low dose raloxifene hydrochloride PO daily on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm A (raloxifene hydrochloride)Questionnaire AdministrationPatients receive low dose raloxifene hydrochloride PO daily on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm A (raloxifene hydrochloride)Raloxifene HydrochloridePatients receive low dose raloxifene hydrochloride PO daily on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm B (bicalutamide)BicalutamidePatients receive low dose bicalutamide PO daily on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm B (bicalutamide)Laboratory Biomarker AnalysisPatients receive low dose bicalutamide PO daily on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm B (bicalutamide)Questionnaire AdministrationPatients receive low dose bicalutamide PO daily on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm C (raloxifene hydrochloride, bicalutamide)Laboratory Biomarker AnalysisPatients receive low dose raloxifene hydrochloride PO daily and low dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm C (raloxifene hydrochloride, bicalutamide)Questionnaire AdministrationPatients receive low dose raloxifene hydrochloride PO daily and low dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm D (raloxifene hydrochloride, bicalutamide)BicalutamidePatients receive high dose raloxifene hydrochloride PO daily and high dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm D (raloxifene hydrochloride, bicalutamide)Laboratory Biomarker AnalysisPatients receive high dose raloxifene hydrochloride PO daily and high dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm D (raloxifene hydrochloride, bicalutamide)Questionnaire AdministrationPatients receive high dose raloxifene hydrochloride PO daily and high dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm D (raloxifene hydrochloride, bicalutamide)Raloxifene HydrochloridePatients receive high dose raloxifene hydrochloride PO daily and high dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm C (raloxifene hydrochloride, bicalutamide)BicalutamidePatients receive low dose raloxifene hydrochloride PO daily and low dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm C (raloxifene hydrochloride, bicalutamide)Raloxifene HydrochloridePatients receive low dose raloxifene hydrochloride PO daily and low dose bicalutamide PO on days 1-30. Treatment repeats every 30 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Collection and interrogation of prostate cancer samplesUp to 5 years

Pathways and biomarkers will be compared to similar analyses that have been and will be performed on in vitro and in vivo experiments. Point estimates and two-sided 95% confidence intervals will be computed.

Secondary Outcome Measures
NameTimeMethod
Change in cancer stage/grade via surgical pathologyBaseline up to the time of prostatectomy

Will be calculated as the total number who were down staged divided by the number of total evaluable patients. A confidence interval for this rate will be calculated based on properties of the binomial distribution. Point estimates and two-sided 95% confidence intervals will be computed.

Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0Up to 30 days

The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.

Percent change in PSA assessed by Prostate Cancer Clinical Trials Working GroupBaseline up to 12 weeks

Will be calculated and displayed using waterfall plots.

Tolerance of therapyUp to 60 days

Proportion of patients who complete 60 days of treatment will be calculated as the number of who completed 60 days of treatment divided by the total number of evaluable patients. A confidence interval for this rate will be calculated based on properties of the binomial distribution. The proportion of patients who experience a particular event will be calculated as the total number who experienced the event of interest divided by the number of total evaluable patients, with appropriate confidence interval.

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