Study of Enzalutamide in Patients With Castration-resistant Prostate Cancer

NCT01942837 | Completed Phase 2 Results DMC

• 1 other identifier: 13-301
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 5

Brief Summary

This research study is evaluating a drug called enzalutamide in metastatic castration resistant prostate cancer. Enzalutamide is already FDA approved for metastatic castration resistant prostate cancer after treatment with chemotherapy. The purpose of this study is to analyze features of tumor specimens sampled prior to therapy and at disease progression to determine why patients respond or stop responding to treatment with Enzalutamide. Prior chemotherapy is not a requirement of this trial.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Enzalutamide; Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Gene Alterations

  Serial biopsies was performed at pre-study and progression to analyze mechanisms of resistance to enzalutamide, such as alterations in AR (mutations, amplifications), tumor suppression genes, DNA repair genes, and SPOP. Whole exome sequencing was performed on tumor tissue biopsies.

  Tumor biopsies were performed at pre-study and progression. Progression occurred up to 41 months after initiation of enzalutamide.

Secondary Outcomes (8)

• Changes in Serum Androgen Concentrations Between Baseline and Subsequent Assessment Visits

  Not collected.

• Number of Participants With a PSA Response

  PSA was measured at pre-treatment, each C1D1 (1 cycle=28 days), end of treatment, and follow-up visits (every 6 months). PSA were measured up to 52 months.

• Duration of PSA Response

  PSA was measured at pre-treatment, each C1D1 (1 cycle=28 days), end of treatment, and follow-up visits (every 6 months). PSA were measured up to 52 months.

• Response of Measurable Disease at Baseline

  Imaging was performed at pre-study and every 12 weeks on treatment. Treatment cycles is 28 days. Patients were assessed up to 41 months.

• Duration of Response of Measurable Disease

  Imaging was performed at pre-study and every 12 weeks on treatment. Treatment cycles is 28 days. Patients were assessed up to 41 months.

Study Arms (1)

Enzalutamide

EXPERIMENTAL

Administration: 160 mg orally once daily with a 28-day cycle. Treatment will be continued until evidence of symptomatic or radiographic progression or the participant is taken off the study for another reason. Dosing: 160 mg orally taken once daily as four 40 mg capsules.

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

Enzalutamide, formerly known as MDV3100, is a rationally-designed second generation AR inhibitor which functions by blocking several steps in the AR signaling cascade. Enzalutamide competitively binds the AR with great potency. Additionally, enzalutamide inhibits nuclear translocation of activated AR and inhibits the association of activated AR with DNA.

Also known as: Xtandi

Enzalutamide

Eligibility Criteria

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

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Be a male ≥ 18 years of age.
• Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate without ≥50% neuroendocrine differentiation or small cell histology.
• Participants must have progressive disease as defined by either:
• Castrate resistant disease as defined by PCWG. Participants must have a rise in PSA on two successive determinations at least one week apart and PSA levels ≥ 2 ng/ml (only the screening PSA needs to be ≥ 2 ng/ml) and testosterone levels \< 50 ng/dL, OR
• Soft tissue progression defined by RECIST 1.1, OR
• Bone disease progression defined by PCWG2 with two or more new lesions on bone scan.
• CRPC with metastatic disease with at least one site of metastatic disease must be amenable to needle biopsy. Soft tissue biopsy sites include: lymph node or visceral metastases. Bone sites include lumbar vertebrae, pelvic bones and long bones. Excluded sites are thoracic, cervical vertebrae, skull and rib lesions. Biopsy site will be selected with guidance of interventional radiologist determining best site to optimize balance of obtaining useful tissue for analysis and minimizing risk.
• Participants without orchiectomy must be maintained on LHRH agonist/antagonist therapy.
• Participants may have had any number of previous hormonal therapies (antiandrogens, steroids, estrogens, finasteride, dutasteride, ketoconazole, abiraterone) provided these were discontinued ≥ 4 weeks before enrollment.
• Participants may have had up to two previous cytotoxic therapeutic regimens provided these were discontinued ≥ 4 weeks before enrollment.
• At least a 4 week interval from previous prostate cancer treatment other than LHRH agonist/antagonist therapy or bisphosphonates to enrollment.
• Participants receiving bisphosphonates therapy can be maintained on this therapy. If participants have not started bisphosphonates, it is recommended that they start treatment after the first biopsy.
• ECOG performance status \< 2 (Karnofsky \>60%, see Appendix A).
• Participants must have normal organ and marrow function as defined below:

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Uncontrolled illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements within 6 months of enrollment.
• Clinically significant heart disease as evidenced by:
• Myocardial infarction within 6 months of enrollment.
• Uncontrolled angina within 6 months of enrollment.
• Congestive heart failure NYHA Class III or IV, or a history of congestive heart failure NYHA Class III or IV in the past, unless a screening ECHO or MUGA within 3 months results in a left ventricular ejection fraction ≥ 45%.
• Clinically significant ventricular arrhythmias.
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
• Bradycardia as indicated by a heart rate \< 50 beats per minute at screening visit.
• Hypotension as indicated by SBP ≤ 85 on 2 consecutive measurements.
• Uncontrolled hypertension as indicated by SBP \> 170 mmHg or DBP \> 105 mmHg on 2 consecutive measurements at screening visit.
• Thromboembolism within 6 months of enrollment.
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
• History of seizure or any condition or concurrent medication that may predispose to seizure.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: superficial bladder cancer, basal cell or squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Medivation, Inc.: collaborator

Study Sites (5)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

South Shore Hospital

Weymouth, Massachusetts, 02190, United States

Location

University of Washington Medical Center/Seattle Cancer Care Alliance

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Sperger JM, Emamekhoo H, McKay RR, Stahlfeld CN, Singh A, Chen XE, Kwak L, Gilsdorf CS, Wolfe SK, Wei XX, Silver R, Zhang Z, Morris MJ, Bubley G, Feng FY, Scher HI, Rathkopf D, Dehm SM, Choueiri TK, Halabi S, Armstrong AJ, Wyatt AW, Taplin ME, Zhao SG, Lang JM. Prospective Evaluation of Clinical Outcomes Using a Multiplex Liquid Biopsy Targeting Diverse Resistance Mechanisms in Metastatic Prostate Cancer. J Clin Oncol. 2021 Sep 10;39(26):2926-2937. doi: 10.1200/JCO.21.00169. Epub 2021 Jul 1.

  PMID: 34197212 DERIVED

MeSH Terms

Interventions

enzalutamide

Results Point of Contact

• Title: Mary-Ellen Taplin, MD
• Organization: Dana-Farber Cancer Institute

mtaplin@partners.org

617-582-7221

Study Officials

• Mary-Ellen Taplin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 4, 2013
• First Posted: September 16, 2013
• Study Start: September 13, 2013
• Primary Completion: December 1, 2021
• Study Completion: September 30, 2022
• Last Updated: October 24, 2022
• Results First Posted: July 5, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)