DEXTER: Dexamethasone Prior to Re-treatment With Enzalutamide in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Previously Treated With Enzalutamide and Docetaxel

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02491411
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 5
• Location: 1
• Arm: 1
• Actual Duration (Months): 30
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Stage IV Prostate Cancer	Drug: Dexamethasone; Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the prostate-specific antigen (PSA) response rate to enzalutamide (Enza) after treatment with dexamethasone (Dex) therapy.

SECONDARY OBJECTIVES:

1. Objective response rate to Enza in patients with measurable disease on computed tomography (CT) scan using Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

2. Time to PSA progression (based upon Prostate Cancer Working Group 2 [PCWG2] criteria) for treatment with Dex.

3. 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]).

4. 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.

5. Response rates to Enza for patients who are AR-V7 positive and AR-V7 negative, respectively, at study entry.

6. 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

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Mar 1, 2018
• Actual Study Completion Date: Mar 1, 2018

Arms and Interventions

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.

Drug: Dexamethasone; Given PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Drug: Enzalutamide; Given PO; Other Names: MDV3100 Xtandi ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment

Outcome Measures

Primary Outcome Measures

1. PSA Response Rate [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.

Secondary Outcome Measures

1. Changes in Quality of Life Assessment Scores, Assessed Using FACIT-Fatigue Scale and RANDSF-36 Surveys [Baseline to up to 4 weeks post-treatment]

   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.

2. Objective Response Rate to Enzalutamide in Patients With Measurable Disease on CT Scan [Up to 4 weeks post-treatment]

   Will estimate 95% confidence interval.

3. Response Rate With Dexamethasone by AR-V7 Status at Study Entry [Baseline]

4. Response Rate With Enzalutamide by AR-V7 Status at Study Entry [Baseline]

5. Time to PSA Progression, Based Upon PCWG2 Criteria, for Treatment With Dexamethasone [Up to 4 weeks post-treatment]

   Will be summarized using Kaplan-Meier approach.

6. Time to Radiographic Progression for Treatment With Dexamethasone [Up to 4 weeks post-treatment]

   Will be summarized using Kaplan-Meier approach.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Samuel Denmeade, Johns Hopkins University/Sidney Kimmel Cancer Center

Study Documents (Full-Text)

• Study Protocol - Aug 24, 2016
• Statistical Analysis Plan - Aug 24, 2016

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02491411
• Other Study ID Numbers: J1548; NCI-2015-00918; IRB00064598; J1548; P30CA006973
• First Posted: Jul 8, 2015
• Last Update Posted: Jul 12, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Prostatic Neoplasms; Dexamethasone; Dexamethasone acetate; Ichthammol; BB 1101

Study Results

Participant Flow

Pre-assignment Detail	One of the five patients enrolled, failed screen due to declining Eastern Cooperative Oncology Group (ECOG) Score of 3, and therefore could not start study.

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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 prostate specific antigen (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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Period Title: Overall Study
STARTED	4
COMPLETED	0
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	4 100%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	4 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	4 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 25%
White	3 75%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	PSA Response Rate
Description	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.
Time Frame	Up to 4 weeks post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected, the study was terminated early due to lower enrollment.

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Measure Participants	0

2. Secondary Outcome

Title	Changes in Quality of Life Assessment Scores, Assessed Using FACIT-Fatigue Scale and RANDSF-36 Surveys
Description	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.
Time Frame	Baseline to up to 4 weeks post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected, the study was terminated early due to lower enrollment.

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Measure Participants	0

3. Secondary Outcome

Title	Objective Response Rate to Enzalutamide in Patients With Measurable Disease on CT Scan
Description	Will estimate 95% confidence interval.
Time Frame	Up to 4 weeks post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected, the study was terminated early due to lower enrollment.

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Measure Participants	0

4. Secondary Outcome

Title	Response Rate With Dexamethasone by AR-V7 Status at Study Entry
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Data was not collected, the study was terminated early due to lower enrollment.

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Measure Participants	0

5. Secondary Outcome

Title	Response Rate With Enzalutamide by AR-V7 Status at Study Entry
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Data was not collected, the study was terminated early due to lower enrollment.

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Measure Participants	0

6. Secondary Outcome

Title	Time to PSA Progression, Based Upon PCWG2 Criteria, for Treatment With Dexamethasone
Description	Will be summarized using Kaplan-Meier approach.
Time Frame	Up to 4 weeks post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected, the study was terminated early due to lower enrollment.

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Measure Participants	0

7. Secondary Outcome

Title	Time to Radiographic Progression for Treatment With Dexamethasone
Description	Will be summarized using Kaplan-Meier approach.
Time Frame	Up to 4 weeks post-treatment

Outcome Measure Data

Analysis Population Description

Data was not collected, the study was terminated early due to lower enrollment.

Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
Measure Participants	0

Adverse Events

Time Frame	4 weeks post treatment for each treatment cycle, up to 1 year
Adverse Event Reporting Description	Every visit
Arm/Group Title	Treatment (Dexamethasone and Enzalutamide)
Arm/Group Description	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. Dexamethasone: Given PO Enzalutamide: Given PO Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies
All Cause Mortality
	Treatment (Dexamethasone and Enzalutamide)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	Treatment (Dexamethasone and Enzalutamide)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Dexamethasone and Enzalutamide)
	Affected / at Risk (%)	# Events
Total	3/4 (75%)
Endocrine disorders
cushingoid (increased appetite and weight )	2/4 (50%)	2
Eye disorders
Eye disorders (reddened eyes)	1/4 (25%)	1
General disorders
fatigue	2/4 (50%)	2
abdominal pain	1/4 (25%)	1
Investigations
Paresthesia	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
left hand cramps	1/4 (25%)	1
Right rib pain	1/4 (25%)	1
Nervous system disorders
insomnia	2/4 (50%)	2
irritability	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
dyspnea	1/4 (25%)	1
SORE THROAT	1/4 (25%)	1
Skin and subcutaneous tissue disorders
BILATERAL LOWER EXTREMITIES EDEMA	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.