Hormone-Resistant Prostate CancerDEXTERNCT02491411
Dexamethasone Prior to Re-treatment With Enzalutamide in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Previously Treated With Enzalutamide and Docetaxel
A study testing Dexamethasone, Enzalutamide and Laboratory Biomarker Analysis in people with Hormone-Resistant Prostate Cancer and Metastatic Prostate Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
This pilot trial studies how well dexamethasone and re-treatment with enzalutamide work in treating patients with prostate cancer that has spread to other places in the body (metastatic), does not respond to hormone therapy (hormone-resistant), and was previously treated with enzalutamide and docetaxel. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hormone-Resistant Prostate Cancer, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma
- What is being tested?
- Dexamethasone, Enzalutamide and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to Mar 2018
- Phase
- Interventional
- 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 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 17Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
About this study
Official title: 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)
This pilot trial studies how well dexamethasone and re-treatment with enzalutamide work in treating patients with prostate cancer that has spread to other places in the body (metastatic), does not respond to hormone therapy (hormone-resistant), and was previously treated with enzalutamide and docetaxel. Dexamethasone treatment may be able to reverse one resistance mechanism to enzalutamide therapy (overabundance of receptors for dexamethasone and other glucocorticoids inside cancer cells) and allow for renewed therapeutic sensitivity to enzalutamide. Androgens (a type of male hormone) can bind to androgen receptors found inside prostate cancer cells, which may cause the cancer cells to grow. Enzalutamide may stop the growth of prostate cancer cells by blocking the activity of the cancer cell androgen receptors. Giving dexamethasone prior to re-treatment with enzalutamide may be a treatment for prostate cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the prostate-specific antigen (PSA) response rate to enzalutamide (Enza) after treatment with dexamethasone (Dex) therapy.
SECONDARY OBJECTIVES:
- 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.
- 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.
- Conditions
- Hormone-Resistant Prostate Cancer, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Stage IV Prostate Cancer
- Being tested
- Dexamethasone, Enzalutamide, Laboratory Biomarker Analysis, Quality-of-Life Assessment
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO
EnzalutamideDrug
Also called MDV3100, Xtandi
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (dexamethasone and enzalutamide) | Experimental | 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. Receives: Drug: Dexamethasone; Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
PSA Response Rate
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.
Measured: Up to 4 weeks post-treatment
Secondary outcomes (6)
Changes in Quality of Life Assessment Scores, Assessed Using FACIT-Fatigue Scale and RANDSF-36 Surveys
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.
Measured: Baseline to up to 4 weeks post-treatment
Objective Response Rate to Enzalutamide in Patients With Measurable Disease on CT Scan
Will estimate 95% confidence interval.
Measured: Up to 4 weeks post-treatment
Response Rate With Dexamethasone by AR-V7 Status at Study Entry
Measured: Baseline
Response Rate With Enzalutamide by AR-V7 Status at Study Entry
Measured: Baseline
Time to PSA Progression, Based Upon PCWG2 Criteria, for Treatment With Dexamethasone
Will be summarized using Kaplan-Meier approach.
Measured: Up to 4 weeks post-treatment
Time to Radiographic Progression for Treatment With Dexamethasone
Will be summarized using Kaplan-Meier approach.
Measured: Up to 4 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2015 (estimated)
- Study startSep 2015
- Primary completionMar 2018
- Study completionMar 2018
Why it stopped: The study is terminated due to lower enrollment
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 Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Samuel Denmeade, Principal investigator, Johns Hopkins University/Sidney Kimmel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02491411
- Sponsor's protocol ID
- J1548
- Other IDs
- NCI-2015-00918, IRB00064598, J1548, P30CA006973
- Acronym
- DEXTER
- Status last verified
- Jul 2018
- First submitted
- 18 Jun 2015
- Last updated
- 12 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02491411
- Acronym / sponsor ID
- DEXTER / J1548
- Conditions
- Hormone-Resistant Prostate Cancer, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, Stage IV Prostate Cancer
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study is terminated due to lower enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2015 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 8 Jul 2015 (estimated)
- Results
- Posted 12 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot trial studies how well dexamethasone and re-treatment with enzalutamide work in treating patients with prostate cancer that has spread to other places in the body (metastatic), does not respond to hormone therapy (hormone-resistant), and was previously treated with enzalutamide and docetaxel. Dexamethasone treatment may be able to reverse one resistance mechanism to enzalutamide therapy (overabundance of receptors for dexamethasone and other glucocorticoids inside cancer cells) and allow for renewed therapeutic sensitivity to enzalutamide. Androgens (a type of male hormone) can bind to androgen receptors found inside prostate cancer cells, which may cause the cancer cells to grow. Enzalutamide may stop the growth of prostate cancer cells by blocking the activity of the cancer cell androgen receptors. Giving dexamethasone prior to re-treatment with enzalutamide may be a treatment for prostate cancer.
Detailed description
PRIMARY OBJECTIVES:
- To determine the prostate-specific antigen (PSA) response rate to enzalutamide (Enza) after treatment with dexamethasone (Dex) therapy.
SECONDARY OBJECTIVES:
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (dexamethasone and enzalutamide) | Experimental | Drug: Dexamethasone, Drug: Enzalutamide, Other: Laboratory Biomarker Analysis, Other: Quality-of-Life AssessmentPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (8 listed)
- 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
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 |
|---|---|---|
| DexamethasoneAlso: Aacidexam, Adexone, Aknichthol Dexa, Alba-DexGiven PO | Drug | Treatment (dexamethasone and enzalutamide) |
| EnzalutamideAlso: MDV3100, XtandiGiven PO | Drug | Treatment (dexamethasone and enzalutamide) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (dexamethasone and enzalutamide) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (dexamethasone and enzalutamide) |
Primary outcome
PSA Response Rate
Time frame: Up to 4 weeks post-treatment
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.
6 secondary outcomes
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
Objective Response Rate to Enzalutamide in Patients With Measurable Disease on CT Scan
Time frame: Up to 4 weeks post-treatment
Response Rate With Dexamethasone by AR-V7 Status at Study Entry
Time frame: Baseline
Response Rate With Enzalutamide by AR-V7 Status at Study Entry
Time frame: Baseline
Time to PSA Progression, Based Upon PCWG2 Criteria, for Treatment With Dexamethasone
Time frame: Up to 4 weeks post-treatment
Time to Radiographic Progression for Treatment With Dexamethasone
Time frame: Up to 4 weeks post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Samuel Denmeade principal investigator
Johns Hopkins University/Sidney Kimmel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dexamethasone, Enzalutamide and Laboratory Biomarker Analysis in people with Hormone-Resistant Prostate Cancer and Metastatic Prostate Carcinoma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site 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 17 inclusion and 8 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: stopped early, as of the sponsor's last update on 12 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2018). 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 Response Rate (time frame: Up to 4 weeks post-treatment). 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 12 Jul 2018.