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

Neoadjuvant Treatment of Prostate Cancer With Bicalutamide and Raloxifene Prior to Radical Prostatectomy

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.

Study Overview

• Status: Withdrawn
• Conditions: Stage II Prostate Adenocarcinoma; Stage I Prostate Adenocarcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Drug: Bicalutamide; Drug: Raloxifene Hydrochloride

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.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (raloxifene hydrochloride); Patients 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Drug: Raloxifene Hydrochloride; Given PO; Other Names: Evista; Keoxifene Hydrochloride; LY-156758; Optruma; Raloxifene HCl; Raloxifene.HCl
Experimental: Arm B (bicalutamide); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Drug: Bicalutamide; Given PO; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334
Experimental: Arm C (raloxifene hydrochloride, bicalutamide); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Drug: Bicalutamide; Given PO; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334; Drug: Raloxifene Hydrochloride; Given PO; Other Names: Evista; Keoxifene Hydrochloride; LY-156758; Optruma; Raloxifene HCl; Raloxifene.HCl
Experimental: Arm D (raloxifene hydrochloride, bicalutamide); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Drug: Bicalutamide; Given PO; Other Names: Casodex; Cosudex; ICI 176,334; ICI 176334; Drug: Raloxifene Hydrochloride; Given PO; Other Names: Evista; Keoxifene Hydrochloride; LY-156758; Optruma; Raloxifene HCl; Raloxifene.HCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collection and interrogation of prostate cancer samples	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.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cancer stage/grade via surgical pathology	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.	Baseline up to the time of prostatectomy
Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0	The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.	Up to 30 days
Percent change in PSA assessed by Prostate Cancer Clinical Trials Working Group	Will be calculated and displayed using waterfall plots.	Baseline up to 12 weeks
Tolerance of therapy	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.	Up to 60 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quality of life assessed using the 6-item Linear Analogue Self-Assessment and the Hormonal Domain scale of the Expanded Prostate Cancer Index Composite survey	Will be examined using stream plots and mean plots with associated two-sided 95% confidence intervals.	Baseline up to 5 years
Change in specific pathways and biomarkers	Continuous biomarker levels will be explored in a graphical manner including mean plots and plots of change and percent change from baseline and other summary measures. Any potential relationships between the baseline level or change in the level of each biomarker and clinical outcome will be further analyzed using Wilcoxon rank sum tests or logistic regression methods, as appropriate. Association between a dichotomized biomarker and overall response will be assessed using a chi-squared test.	Baseline up to 5 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Erik Castle, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2017
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: May 8, 2017
• First Submitted That Met QC Criteria: May 8, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Adenocarcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Androgen Antagonists; Raloxifene Hydrochloride; Bicalutamide
• Other Study ID Numbers: MC1552 (Other Identifier: Mayo Clinic in Arizona); P30CA015083 (U.S. NIH Grant/Contract); NCI-2017-00773 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No