Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer (Doce/Enza)

• ClinicalTrials.gov Identifier: NCT02685267
• Recruitment Status: Terminated
• First Posted: February 18, 2016
• Results First Posted: March 12, 2021
• Last Update Posted: April 9, 2021
• Sponsor: Prostate Cancer Clinical Trials Consortium
• Collaborators: University of Chicago; Astellas Pharma Inc
• Information provided by (Responsible Party): Prostate Cancer Clinical Trials Consortium

Tracking Information

• First Submitted Date: February 9, 2016
• First Posted Date: February 18, 2016
• Results First Submitted Date: July 29, 2019
• Results First Posted Date: March 12, 2021
• Last Update Posted Date: April 9, 2021
• Study Start Date: February 2016
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 9, 2021)

Progression-free Survival (Radiographic or Per PCWG2 Criteria) [ Time Frame: 1 year ]

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.

• Original Primary Outcome Measures (submitted: February 12, 2016): Progression-free survival (radiographic or per PCWG2 criteria) [ Time Frame: 1 year ]

Current Secondary Outcome Measures (submitted: March 11, 2021)

• PSA Response in the Standard Treatment Arm and Experimental Treatment Arm [ Time Frame: Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), Day 231, and every 21 days through study completion (an average of 1 year) ]
  PSA response measured according to Prostate Cancer Working Group 2 (PCWG2). The study was terminated after only 9 patients enrolled, 5 to the standard of care docetaxel/prednisone arm and 4 to experimental docetaxel/prednisone/enzalutamide arm.
• Overall Survival [ Time Frame: At both 1 year and 2 years from treatment start ]

Original Secondary Outcome Measures (submitted: February 12, 2016)

• PSA response in the standard treatment arm and experimental treatment arm [ Time Frame: 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 [ Time Frame: At both 1 year and 2 years from treatment start ]

Current Other Pre-specified Outcome Measures (submitted: March 9, 2021)

• Quality of Life (QOL) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), and every 63 days through study completion (an average of 1 year) ]

Original Other Pre-specified Outcome Measures (submitted: February 12, 2016)

• Quality of life (QOL) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), and every 63 days through study completion (an average of 1 year) ]

Descriptive Information

• Brief Title: Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer
• Official Title: A Phase II Randomized Prospective Trial of Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer (CRPC) Patients Progressing on Enzalutamide

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Drug: Docetaxel
• Drug: Enzalutamide
• Drug: Prednisone

Study Arms

• Active Comparator: Docetaxel/Prednisone
  Docetaxel 75 mg/m2 day 1 (every 21-days) plus prednisone 5 mg po bid throughout
  Interventions:

  • Drug: Docetaxel
  • Drug: Prednisone
• Active Comparator: Docetaxel/Prednisone + Enzalutamide
  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.
  Interventions:

  • Drug: Docetaxel
  • Drug: Enzalutamide
  • Drug: Prednisone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 12, 2017): 9
• Original Estimated Enrollment (submitted: February 12, 2016): 100
• Actual Study Completion Date: August 2017
• Actual Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner
  • Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner
  • Tubal litigation in the female partner
  • Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy) for >6 months
• Patients must have adequate organ and marrow function as defined below
• Leukocytes >3,000/mm3
• absolute neutrophil count >1,500/mm3
• platelets >100,000/mm3
• total bilirubin within normal institutional limits (or <2X the upper limit of normal in those with Gilbert's disease)
• AST(SGOT)/ALT(SGPT) <1.5 X institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance* >45 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Estimated life expectancy of > 6 months
• Able to swallow the study drug as prescribed and comply with study requirements

Exclusion Criteria:

• 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02685267
• Other Study ID Numbers: c13-126
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Prostate Cancer Clinical Trials Consortium
• Original Responsible Party: Same as current
• Current Study Sponsor: Prostate Cancer Clinical Trials Consortium
• Original Study Sponsor: Same as current

Collaborators

• University of Chicago
• Astellas Pharma Inc

• Investigators: Not Provided
• PRS Account: Prostate Cancer Clinical Trials Consortium
• Verification Date: March 2021