Molecular Features and Pathways in Predicting Drug Resistance in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide

• Status: Completed
• Trial end date: 2020-02-27
• Target enrollment: 0
• Participant gender: Male

Summary

This research trial studies molecular features and pathways in predicting drug resistance in patients with castration-resistant prostate cancer that has spread to other parts of the body and who are receiving enzalutamide. Studying samples of blood and tissue in the laboratory from patients receiving enzalutamide may help doctors learn more about molecular features and pathways that may cause prostate cancer to be resistant to the drug.

• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI); Oregon Health and Science University; United States Department of Defense

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features

• Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial

• Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy

• Willingness to undergo a tumor biopsy at baseline and at disease progression

• Serum testosterone level < 50 ng/dL at screening

• Progressive disease by PSA or imaging in the setting of medical or surgical castration; disease progression for study entry is defined as one or more of the following three criteria:

• PSA progression defined by a minimum of three rising PSA levels with an interval of >= 1 week between each determination; the PSA value at screening should be >= 2 ug/L (2 ng/ml)

• Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

• Bone disease progression defined by two or more new lesions on bone scan

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Clinically able, in the opinion of the investigator, to receive MDV3100 (enzalutamide)

• Willing and able to give informed consent

• A minimum of 4 weeks elapsed off of anti-androgen therapy prior to enrollment for flutamide and 6 weeks for bicalutamide and nilutamide without evidence of an anti-androgen withdrawal response; patients who NEVER HAD A PSA decline with the most recent anti-androgen therapy or in whom the response to the most recent anti-androgen was for < 3 months require only a 2 week washout period prior to first dose of study drug

Exclusion Criteria:

• Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment

• Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed)

• Platelet count < 75,000/uL

• Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time PTT > 1.5 times the institutional upper limit of normal (ULN)

• Structurally unstable bone lesions suggesting impending fracture

• Previous treatment with MDV3100, ARN-509, or BMS-641988

• Medical contraindications to stopping aspirin, Coumadin or other anticoagulants for 1 week prior to image-guided tumor biopsies

• Plans to initiate treatment with an investigational agent while on study prior to discontinuation of MDV3100 treatment

• A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm