Hormone-resistant Prostate CancerPhase 1/2NCT02012296
Enzalutamide and Mifepristone in Treating Patients With Metastatic Hormone Resistant Prostate Cancer
A Phase 1/2 study testing enzalutamide, mifepristone and laboratory biomarker analysis in people with Hormone-resistant Prostate Cancer and Recurrent Prostate Cancer, run by University of Chicago at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer
- What is being tested?
- enzalutamide, mifepristone and laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 4 sitesUnited States
- Study dates
- 13 Dec 2013to 1 Aug 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- 2 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
Show all 20Show fewer
- 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
- Denosumab or zoledronic acid are allowed
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Total bilirubin =< 1.5 x the upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637-1470
Cancer Care Specialists of Central Illinois (Decatur) /Decatur Memorial Hospital
Decatur, Illinois, 62526
Wayne State University Karmanos Cancer Institute
Detroit, Michigan, 48201
NorthShore University Health System
Evanston, Illinois, 60201
About this study
Official title: A Phase I/II Trial of Enzalutamide Plus the Glucocorticoid Receptor Antagonist Mifepristone for Patients With Metastatic Castration Resistant Prostate Cancer (CRPC)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To establish the safe and pharmacologically active doses of mifepristone and enzalutamide to use in combination. (Phase I) II. To determine if mifepristone in combination with enzalutamide prolongs time to prostate-specific antigen (PSA) progression compared to enzalutamide alone in patients with metastatic castration resistant prostate cancer. (Phase II)
SECONDARY OBJECTIVES:
- To evaluate the effect of mifepristone on endocrine biomarkers such as serum cortisol and thyrotropin.
II. To determine the effect of mifepristone on enzalutamide clearance and steady state enzalutamide exposure.
III. To determine if mifepristone affects PSA response rate when added to enzalutamide.
IV. To determine if mifepristone when added to mifepristone prolongs radiographic and clinical progression free survival according to standard working group criteria.
- To explore the role of glucocorticoid receptor (GR) and androgen receptor (AR) protein expression within circulating tumor cells as a pharmacodynamic biomarker for mifepristone and enzalutamide in castration resistant prostate cancer (CRPC).
VI. To explore the expression of GR and down-stream AR/GR targets in metastatic tumor specimen prior to combination drug administration and at clinical progression.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
PHASE I: Patients receive enzalutamide orally (PO) on days 1-57 and mifepristone PO on days 29-57. Treatment continues in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients receive enzalutamide PO for 12 weeks per standard of care. Patients are then randomized to 1 of 2 treatment arms.
ARM I: Patients receive enzalutamide PO per standard of care.
ARM II: Patients receive enzalutamide PO and mifepristone PO.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
- Being tested
- enzalutamide, mifepristone, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enzalutamideDrug
Also called MDV3100, selective androgen receptor modulator MDV3100, XTANDI
Given PO
mifepristoneDrug
Also called Mifegyne, Mifeprex, RU-38486
Given PO
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (enzalutamide) | Active comparator | Patients receive enzalutamide PO per standard of care. Receives: Drug: enzalutamide; Other: laboratory biomarker analysis; Other: pharmacological study |
| Treatment (enzalutamide, mifepristone) | Experimental | Patients receive enzalutamide PO and mifepristone PO. Receives: Drug: enzalutamide; Drug: mifepristone; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 3 years, measured from randomization
Secondary outcomes (6)
Radiographic PFS
Radiographic progression or death from any cause.
Measured: Up to 3 years, measured from randomization
Number of Participants With Positive AR Expression Within Circulating Tumor Cells (CTCs)
Positive/negative classification with positive defined as a cytokeratin cell for whom there was an androgen receptor > 0
Measured: Week 12 (randomization)
Number of Participants With Positive GR Expression Within Circulating Tumor Cells (CTCs)
Positive/negative classification with positive defined as a cytokeratin cell for whom there was an glucocorticoid receptor > 0
Measured: Week 12 (randomization)
Testosterone
Change from week 12 to week 16
Measured: 12 to 16 weeks
Thyroid Stimulating Hormone
Change in log(TSH) from week 12 to week 16
Measured: 12 to 16 weeks
Cortisol
Change in log(Cortisol) from week 12 to week 16
Measured: 12 to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study start13 Dec 2013
- Primary completion10 Jun 2019
- Study completion1 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hormone-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- We report here the phase 2 results
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Russell Szmulewitz, Principal investigator, University of Chicago Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012296
- Sponsor's protocol ID
- IRB13-0979
- Other IDs
- NCI-2013-02151, CDMRP-PC121149, IRB13-0979, P30CA014599
- Status last verified
- Jun 2022
- First submitted
- 10 Dec 2013
- Last updated
- 13 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Enzalutamide Plus the Glucocorticoid Receptor Antagonist Mifepristone for Patients With Metastatic Castration Resistant Prostate Cancer (CRPC)
- ClinicalTrials.gov ID
- NCT02012296
- Acronym / sponsor ID
- IRB13-0979
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Dec 2013 (actual)
- Primary completion
- 10 Jun 2019 (actual)
- Study completion
- 1 Aug 2020 (actual)
- First posted
- 16 Dec 2013 (estimated)
- Results
- Posted 13 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To establish the safe and pharmacologically active doses of mifepristone and enzalutamide to use in combination. (Phase I) II. To determine if mifepristone in combination with enzalutamide prolongs time to prostate-specific antigen (PSA) progression compared to enzalutamide alone in patients with metastatic castration resistant prostate cancer. (Phase II)
SECONDARY OBJECTIVES:
- To evaluate the effect of mifepristone on endocrine biomarkers such as serum cortisol and thyrotropin.
II. To determine the effect of mifepristone on enzalutamide clearance and steady state enzalutamide exposure.
III. To determine if mifepristone affects PSA response rate when added to enzalutamide.
IV. To determine if mifepristone when added to mifepristone prolongs radiographic and clinical progression free survival according to standard working group criteria.
- To explore the role of glucocorticoid receptor (GR) and androgen receptor (AR) protein expression within circulating tumor cells as a pharmacodynamic biomarker for mifepristone and enzalutamide in castration resistant prostate cancer (CRPC).
VI. To explore the expression of GR and down-stream AR/GR targets in metastatic tumor specimen prior to combination drug administration and at clinical progression.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
PHASE I: Patients receive enzalutamide orally (PO) on days 1-57 and mifepristone PO on days 29-57. Treatment continues in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients receive enzalutamide PO for 12 weeks per standard of care. Patients are then randomized to 1 of 2 treatment arms.
ARM I: Patients receive enzalutamide PO per standard of care.
ARM II: Patients receive enzalutamide PO and mifepristone PO.
In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- We report here the phase 2 results
| Arm | Type | Receives |
|---|---|---|
| Treatment (enzalutamide) | Active comparator | Drug: enzalutamide, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive enzalutamide PO per standard of care. |
| Treatment (enzalutamide, mifepristone) | Experimental | Drug: enzalutamide, Drug: mifepristone, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive enzalutamide PO and mifepristone PO. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
- For Phase II portion of the study:
- Subjects must have documented clinically stable disease or better during the screening period of the study as defined by all of the following:
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| enzalutamideAlso: MDV3100, selective androgen receptor modulator MDV3100, XTANDIGiven PO | Drug | Treatment (enzalutamide), Treatment (enzalutamide, mifepristone) |
| mifepristoneAlso: Mifegyne, Mifeprex, RU-38486Given PO | Drug | Treatment (enzalutamide, mifepristone) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (enzalutamide), Treatment (enzalutamide, mifepristone) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (enzalutamide), Treatment (enzalutamide, mifepristone) |
Primary outcome
PSA Progression-free Survival
Time frame: Up to 3 years, measured from randomization
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.
6 secondary outcomes
Radiographic PFS
Time frame: Up to 3 years, measured from randomization
Number of Participants With Positive AR Expression Within Circulating Tumor Cells (CTCs)
Time frame: Week 12 (randomization)
Number of Participants With Positive GR Expression Within Circulating Tumor Cells (CTCs)
Time frame: Week 12 (randomization)
Testosterone
Time frame: 12 to 16 weeks
Thyroid Stimulating Hormone
Time frame: 12 to 16 weeks
Cortisol
Time frame: 12 to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hormone-resistant Prostate Cancer
RecruitingObservational study
An Observational Study to Learn More About the Safety of Darolutamide in Men With Prostate Cancer in Korea
Non-metastatic Castration-resistant Prostate Cancer, Metastatic Hormone-sensitive Prostate Cancer
RecruitingPhase 1
JUR-003 in Adult Patients With Metastatic Prostate Cancer
Metastatic Castration Resistant Prostate Cancer, Oligometastatic Prostate Cancer (OMPC)
RecruitingPhase 3
A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1)
Metastatic Castration Resistant Prostate Cancer
RecruitingPhase 1
A Study of Pasritamig (JNJ-78278343) in Combination With Other Agents for Metastatic Prostate Cancer
Metastatic Castration-resistant Prostate Neoplasms, Metastatic Hormone-sensitive Prostate Cancer
RecruitingPhase 1/2
Study of HLD-0915 (JNJ-101556143) in Patients With Metastatic Prostate Cancer
Metastatic Prostate Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Russell Szmulewitz principal investigator
University of Chicago Comprehensive Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing enzalutamide, mifepristone and laboratory biomarker analysis in people with Hormone-resistant Prostate Cancer and Recurrent Prostate Cancer, run by University of Chicago at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PSA Progression-free Survival (time frame: Up to 3 years, measured from randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2022.