Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer

NCT02685267 | Terminated Phase 2 Results

• 1 other identifier: c13-126
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

Brief Summary

This is a prospective randomized phase II clinical trial where patients who are receiving enzalutamide in the pre-chemotherapy space are randomized upon objective progression (radiographic and/or clinical per PCWG2 criteria) to docetaxel/prednisone alone or the same combination plus enzalutamide. The primary aim is to evaluate whether continuing enzalutamide in combination with docetaxel in patients who failed or progressed while on enzalutamide would increase progression-free survival (PFS) by 4 months. The secondary end points are PSA responses, percent of patients alive at 1 and 2 years, decline in circulating tumor cells (CTCs), and quality of life (QOL) using validated scales.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (Radiographic or Per PCWG2 Criteria)

  The primary endpoint of the study is progression-free survival (PFS), defined as the time from randomization to disease progression. Progression will be evaluated using a combination of RECIST and Prostate Cancer Working Group 2 guidelines.

  1 year

Secondary Outcomes (2)

• PSA Response in the Standard Treatment Arm and Experimental Treatment Arm

  Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), Day 231, and every 21 days through study completion (an average of 1 year)

• Overall Survival

  At both 1 year and 2 years from treatment start

Other Outcomes (3)

• Quality of Life (QOL)

  Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), Day 231 and every 21 days through study completion (an average of 1 year)

• Circulating Tumor Cells (CTCs)

  Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), and every 63 days through study completion (an average of 1 year)

• Analysis of Androgen Receptor Splice Variant

  Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), and every 63 days through study completion (an average of 1 year)

Study Arms (2)

Docetaxel/Prednisone

ACTIVE COMPARATOR

Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout

Drug: Docetaxel; Drug: Prednisone

Docetaxel/Prednisone + Enzalutamide

ACTIVE COMPARATOR

Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout plus Enzalutamide 160 mg daily throughout. Subjects will continue enzalutamide until PD after 10 cycles of docetaxel.

Drug: Docetaxel; Drug: Enzalutamide; Drug: Prednisone

Interventions

Docetaxel DRUG

Docetaxel/Prednisone; Docetaxel/Prednisone + Enzalutamide

Enzalutamide DRUG

Docetaxel/Prednisone + Enzalutamide

Prednisone DRUG

Docetaxel/Prednisone; Docetaxel/Prednisone + Enzalutamide

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent and HIPAA authorization for the release of personal health information.
• NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Males 18 years of age and above
• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Having documented disease progression on enzalutamide defined by 1 or more of the following criteria:
• PSA progression according to PCWG2 criteria with 3 consecutive rising PSA measurements, all collected at least 1 week apart
• Radiographic progression in soft tissue or bone by modified RECIST 1.1 for subjects with measurable disease; or
• Bone disease progression defined by 2 or more new lesions on 2 consecutive bone scans in the absence of falling PSA
• Patients who have not had a bilateral orchiectomy must have a plan to maintain effective GnRG-analogue therapy for the duration of the trial
• Serum testosterone level \< 50 ng/dL at Screening visit
• ECOG PS: 0-1
• Throughout the study, male patients and their female partners of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration. Two acceptable methods of birth control thus include the following:
• Condom (barrier method of contraception even if having sex with a pregnant woman)
• One of the following is required:
• Established use of oral, injected, or implanted hormonal method of contraception by the female partner

You may not qualify if:

• Prior treatment with docetaxel-based chemotherapy
• Prior treatment with abiraterone acetate
• Prior treatment with cabazitaxel
• Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
• Ongoing investigational treatment
• Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus, cardiac disease that would, in the opinion of the investigator, make this protocol unreasonably hazardous
• Major surgery within 4 weeks of enrollment
• Use of an investigational therapeutic agent with 4 weeks of enrollment
• History of seizure or any condition that may predispose to seizure.
• History of loss of consciousness or transient ischemic attack within 12 months of enrollment
• Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease) within last 3 months
• Grade \> 2 treatment-related toxicity from prior therapy
• History of hypersensitivity to polysorbate 80
• Any known allergy to the compounds under investigation
• Any other condition which, in the opinion of the Investigator, would preclude participation in this trial

Sponsors & Collaborators

• Prostate Cancer Clinical Trials Consortium: lead
• University of Chicago: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (5)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSytem - Kellogg Cancer Center

Evanston, Illinois, 60201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Univesity of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; enzalutamide; Prednisone

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Jake Vinson
• Organization: PCCTC

vinsonj@mskcc.org

646-422-4383

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: February 18, 2016
• Study Start: February 1, 2016
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: April 9, 2021
• Results First Posted: March 12, 2021

Record last verified: 2021-03

Locations

US (5)