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

NCT02491411 | Terminated Results DMC

• 4 other identifiers: J1548NCI-2015-00918IRB00064598P30CA006973
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  Baseline to up to 4 weeks post-treatment

• Objective Response Rate to Enzalutamide in Patients With Measurable Disease on CT Scan

  Up to 4 weeks post-treatment

• Response Rate With Dexamethasone by AR-V7 Status at Study Entry

  Baseline

• Response Rate With Enzalutamide by AR-V7 Status at Study Entry

  Baseline

• Time to PSA Progression, Based Upon PCWG2 Criteria, for Treatment With Dexamethasone

  Up to 4 weeks post-treatment

Study Arms (1)

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.

Drug: Dexamethasone; Drug: Enzalutamide; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment

Interventions

Dexamethasone DRUG

Given PO

Also known as: 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

Treatment (dexamethasone and enzalutamide)

Enzalutamide DRUG

Given PO

Also known as: MDV3100, Xtandi

Treatment (dexamethasone and enzalutamide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dexamethasone and enzalutamide)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (dexamethasone and enzalutamide)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed adenocarcinoma of the prostate
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; enzalutamide

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Samuel Denmeade
• Organization: SKCCC at JHU

denmesa@jhmi.edu

410-955-8875

Study Officials

• Samuel Denmeade

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2015
• First Posted: July 8, 2015
• Study Start: September 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: July 12, 2018
• Results First Posted: July 12, 2018

Record last verified: 2018-07

Locations

US (1)