- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02491411
Dexamethasone Prior to Re-treatment With Enzalutamide in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Previously Treated With Enzalutamide and Docetaxel (DEXTER)
A Pilot Study of Dexamethasone Therapy Prior to Rechallenge With Enzalutamide in Men With Metastatic Castration-Resistant Prostate Cancer Dex EXTends Enza Response (The DEXTER Trial)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the prostate-specific antigen (PSA) response rate to enzalutamide (Enza) after treatment with dexamethasone (Dex) therapy.
SECONDARY OBJECTIVES:
I. Objective response rate to Enza in patients with measurable disease on computed tomography (CT) scan using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
II. Time to PSA progression (based upon Prostate Cancer Working Group 2 [PCWG2] criteria) for treatment with Dex.
III. Effect of each treatment on quality of life as assessed by patient completion of validated instruments (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue Scale, RAND Short Form-36 [RANDSF-36]).
IV. PSA response rates to Dex for patients who are androgen receptor splice variant 7 (AR-V7) positive and AR-V7 negative, respectively, at study entry.
V. Response rates to Enza for patients who are AR-V7 positive and AR-V7 negative, respectively, at study entry.
VI. Percentage of patients who are AR-V7 positive at study entry who are AR-V7 negative at time of initiation of Enza, or vice-versa.
OUTLINE:
Patients receive dexamethasone orally (PO) once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity until there is evidence of PSA progression, clinical disease progression, or radiographic disease progression. At time of progression, dexamethasone will be stopped via a rapid taper over one week if patients were treated for over 30 days. Patients then receive enzalutamide PO once daily on days 1-28. Treatment repeats every 28 days for up to 3 courses in the absence of clinical disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate
- Patients must have metastatic disease radiographically documented by CT/magnetic resonance imaging (MRI) or bone scan; measurable disease is not necessary for inclusion
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of greater than 3 months in the opinion of the investigator
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Hemoglobin >= 8; transfusion is allowed
- Total bilirubin =< 1.5 x institutional 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
- Creatinine clearance >= 30 by Cockcroft-Gault formula
- Patients must have progression after prior treatment with Enza at any point in the disease course (pre- or post-chemotherapy)
- Patients must have progressed after prior treatment with docetaxel; docetaxel must have specifically been given for castration-resistant metastatic disease
- Prior treatment with other second line hormone therapy is allowed (e.g. flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, ARN-509); patients must be off these therapies for at least 4 weeks prior to starting treatment
- Prior treatment with Xofigo (223Radium), Provenge, mitoxantrone and cabazitaxel is allowed
- Patients must have rising PSA on two successive measurements, at least 2 weeks apart
- Patient must be treated with continuous androgen ablative therapy (e.g. goserelin, leuprolide, triptorelin, or degarelix, if he has not had prior surgical castration) and have castrate levels of testosterone (< 50 ng/dL or 1.7 nmol/L)
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (persistent toxicity >= grade 1)
- Patients who have received any other investigational agents within the last 4 weeks
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Dex or Enza
- Any use of systemic corticosteroids in the prior 4 weeks
- Uncontrolled diabetes mellitus
- History of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformations
- Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) are ineligible (e.g. gemfibrozil, rifampin, trimethoprim, pioglitazone)
- 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 or geographical condition that would limit compliance with study requirements
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (dexamethasone and enzalutamide)
Patients receive dexamethasone PO once daily on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity until there is evidence of PSA progression, clinical disease progression, or radiographic disease progression.
At time of progression, dexamethasone will be stopped via a rapid taper over one week if patients were treated for over 30 days.
Patients then receive enzalutamide PO once daily on days 1-28.
Treatment repeats every 28 days for up to 3 courses in the absence of clinical disease progression or unacceptable toxicity.
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Correlative studies
Ancillary studies
Other Names:
Given PO
Other Names:
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PSA Response Rate
Time Frame: Up to 4 weeks post-treatment
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PSA response rate is defined as the proportion of subjects with a >= 50% PSA decline from baseline level when starting enzalutamide and maintained for >= 4 weeks at any time-point after receiving enzalutamide.
Will determine its corresponding 95% confidence interval.
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Up to 4 weeks post-treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Quality of Life Assessment Scores, Assessed Using FACIT-Fatigue Scale and RANDSF-36 Surveys
Time Frame: Baseline to up to 4 weeks post-treatment
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Summary statistics of the scores will be reported at baseline before starting dexamethasone and each follow-up time during the treatment of dexamethasone and enzalutamide.
Changes in quality of life scores over the course of the study will be computed and their significance will be evaluated by paired-sample t-tests.
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Baseline to up to 4 weeks post-treatment
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Objective Response Rate to Enzalutamide in Patients With Measurable Disease on CT Scan
Time Frame: Up to 4 weeks post-treatment
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Will estimate 95% confidence interval.
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Up to 4 weeks post-treatment
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Response Rate With Dexamethasone by AR-V7 Status at Study Entry
Time Frame: Baseline
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Baseline
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Response Rate With Enzalutamide by AR-V7 Status at Study Entry
Time Frame: Baseline
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Baseline
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Time to PSA Progression, Based Upon PCWG2 Criteria, for Treatment With Dexamethasone
Time Frame: Up to 4 weeks post-treatment
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Will be summarized using Kaplan-Meier approach.
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Up to 4 weeks post-treatment
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Time to Radiographic Progression for Treatment With Dexamethasone
Time Frame: Up to 4 weeks post-treatment
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Will be summarized using Kaplan-Meier approach.
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Up to 4 weeks post-treatment
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Samuel Denmeade, Johns Hopkins University/Sidney Kimmel Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Dermatologic Agents
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Ichthammol
Other Study ID Numbers
- J1548 (Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center)
- P30CA006973 (U.S. NIH Grant/Contract)
- NCI-2015-00918 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- IRB00064598
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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