Enzalutamide and Mifepristone in Treating Patients With Metastatic Hormone Resistant Prostate Cancer

NCT02012296 | Completed Phase 1 Results

• 4 other identifiers: IRB13-0979NCI-2013-02151CDMRP-PC121149P30CA014599
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 4

Brief Summary

This partially randomized phase I/II trial studies the side effects and best dose of enzalutamide and mifepristone when given together and to see how well they work in treating patients with metastatic hormone resistant prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as enzalutamide and mifepristone, may lessen the amount of androgens made by the body. It is not yet known whether enzalutamide is more effective with or without mifepristone in treating patients with prostate cancer.

Conditions

Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• PSA Progression-free Survival

  PSA progression was defined as a PSA that is ≥1.25 times (25% increase) the PSA at randomization (week 12) and an absolute 5 ng/ml increase. PSA progression-free survival is PSA progression or death from any cause.

  Up to 3 years, measured from randomization

Secondary Outcomes (6)

• Radiographic PFS

  Up to 3 years, measured from randomization

• Number of Participants With Positive AR Expression Within Circulating Tumor Cells (CTCs)

  Week 12 (randomization)

• Number of Participants With Positive GR Expression Within Circulating Tumor Cells (CTCs)

  Week 12 (randomization)

• Testosterone

  12 to 16 weeks

• Thyroid Stimulating Hormone

  12 to 16 weeks

Study Arms (2)

Treatment (enzalutamide)

ACTIVE COMPARATOR

Patients receive enzalutamide PO per standard of care.

Drug: enzalutamide; Other: laboratory biomarker analysis; Other: pharmacological study

Treatment (enzalutamide, mifepristone)

EXPERIMENTAL

Patients receive enzalutamide PO and mifepristone PO.

Drug: enzalutamide; Drug: mifepristone; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

enzalutamide DRUG

Given PO

Also known as: MDV3100, selective androgen receptor modulator MDV3100, XTANDI

Treatment (enzalutamide); Treatment (enzalutamide, mifepristone)

mifepristone DRUG

Given PO

Also known as: Mifegyne, Mifeprex, RU-38486

Treatment (enzalutamide, mifepristone)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzalutamide); Treatment (enzalutamide, mifepristone)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (enzalutamide); Treatment (enzalutamide, mifepristone)

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed prostate cancer
• Evidence of castrate testosterone level \< 50 ng/dL (or surgical castration)
• For Phase I portion of the study: evidence of disease progression:
• or more new lesions on bone scan or
• Progressive disease on computed tomography (CT)/magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria or
• Rising PSA: PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart
• For Phase II portion of the study:
• Subjects must be on enzalutamide for metastatic CRPC and within the first 12 weeks of enzalutamide at 160mg/day
• Record of subject's enzalutamide start date and baseline PSA (within 28 days of starting) before starting enzalutamide available
• Subjects must have documented clinically stable disease or better during the screening period of the study as defined by all of the following:
• PSA =\<1.25 times the PSA at start of enzalutamide
• Lack of radiographic progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Prostate Cancer Working Group Criteria
• Clinically stable as confirmed by treating physician
• Any prior therapy for castrate disease is acceptable except prior specific cytochrome P450 family 17 (CYP17) antagonists (e.g. abiraterone acetate, orteronel) or prior second generation AR antagonists (e.g. enzalutamide or ARN509) which are excluded other than enzalutamide as specified for phase II portion; a minimum washout of 28 days for any other anticancer therapy prior to first dose of study drug is required (only applicable for phase I)
• Any other radiotherapy or radionuclide require 28-day washout prior to first dose of study drug

You may not qualify if:

• Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid within 2 weeks prior to first dose of study drug
• Inability to swallow capsules or known gastrointestinal malabsorption
• History of other malignancies, with the exception of: adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 solid tumor malignancies who are without evidence of disease, or other solid tumors curatively treated with no evidence of disease for \>= 5 years from enrollment
• Blood pressure that is not controlled despite \> 2 oral agents (systolic blood pressure \[SBP\] \> 160 and diastolic blood pressure \[DBP\] \> 90 documented during the screening period with no subsequent blood pressure readings \< 160/100)
• History of seizure disorder or active use of anticonvulsants
• Corrected QT interval (QTc) on electrocardiogram (EKG) \> 450 msec
• Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled
• Active psychiatric illness/social situations that would limit compliance with protocol requirements
• New York Heart Association (NYHA) class II, NYHA class III, or IV congestive heart failure (any symptomatic heart failure)
• Concurrent therapy with strong inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) due to concerning possible drug-drug interactions

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637-1470, United States

Location

Cancer Care Specialists of Central Illinois (Decatur) /Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Wayne State University Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Mifepristone

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)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Theodore Karrison
• Organization: University of Chicago

tkarrison@health.bsd.uchicago.edu

773-702-9326

Study Officials

• Russell Szmulewitz

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We report here the phase 2 results

Study Record Dates

• First Submitted: December 10, 2013
• First Posted: December 16, 2013
• Study Start: December 13, 2013
• Primary Completion: June 10, 2019
• Study Completion: August 1, 2020
• Last Updated: July 13, 2022
• Results First Posted: July 13, 2022

Record last verified: 2022-06

Locations

US (4)