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A Study to Assess the Benefit of Treatment Beyond Progression With Enzalutamide in Men Who Are Starting Treatment With Docetaxel After Worsening of Their Prostate Cancer When Taking Enzalutamide Alone (PRESIDE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02288247
Recruitment Status : Active, not recruiting
First Posted : November 11, 2014
Last Update Posted : July 15, 2020
Sponsor:
Collaborator:
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe Ltd. )

Brief Summary:
The purpose of the study is to understand if there is benefit in continued treatment with a medicine called enzalutamide, when starting treatment with docetaxel and prednisolone (a standard chemotherapy for prostate cancer), after the prostate cancer has gotten worse when treated with enzalutamide alone.

Condition or disease Intervention/treatment Phase
Metastatic Castration Resistant Prostate Cancer Drug: Enzalutamide Drug: Docetaxel Drug: Prednisolone Drug: Placebo Phase 3

Detailed Description:

The study will be conducted in consecutive periods of open label treatment with enzalutamide followed by randomized double-blind treatment with continued enzalutamide or placebo, in combination with docetaxel and prednisolone.

Open Label (Period 1)

Participants will receive open label treatment with enzalutamide. At week 13, all participants will be assessed by prostate-specific antigen (PSA) and imaging. Participants with no confirmed PSA response or evidence of radiographic progression will be ineligible for participation in Period 2 and will typically have safety follow up; however, Period 1 treatment may continue for some participants as long as the investigator considers it to be of clinical benefit (stopping on initiation of any new antineoplastic therapy). Participants with confirmed PSA response will continue Period 1 until disease progression.

Enrollment to Period 2 will cease after approximately 274 participants have been enrolled or 182 primary endpoint events have been reached, whichever occurs first. Participants who are not randomized into period 2 at this time may continue receiving open label treatment in an extension period.

Randomization (Double Blind) (Period 2)

Participants with confirmed disease progression on enzalutamide alone who continue to meet all eligibility criteria may proceed to randomization. Treatment allocation will be in a 1:1 ratio, stratified by disease progression in Period 1 to the following treatments:

  • Enzalutamide with docetaxel and prednisolone
  • Placebo with docetaxel and prednisolone

Any ongoing participants in Period 2 at the point of unblinding in the enzalutamide+docetaxel arm that are still receiving and benefitting from enzalutamide treatment , will have the option to continue treatment via an extension period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 690 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo-Controlled, Phase IIIb Study of the Efficacy and Safety of Continuing Enzalutamide in Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer Patients Treated With Docetaxel Plus Prednisolone Who Have Progressed on Enzalutamide Alone
Actual Study Start Date : December 1, 2014
Actual Primary Completion Date : April 30, 2020
Estimated Study Completion Date : September 2021


Arm Intervention/treatment
Experimental: Enzalutamide with docetaxel + prednisolone
Continued treatment with enzalutamide after adding docetaxel and prednisolone
Drug: Enzalutamide
Oral
Other Names:
  • Xtandi
  • ASP9785

Drug: Docetaxel
intravenous infusion

Drug: Prednisolone
Oral

Placebo Comparator: Placebo with docetaxel + prednisolone
Treatment with placebo after adding docetaxel and prednisolone
Drug: Docetaxel
intravenous infusion

Drug: Prednisolone
Oral

Drug: Placebo
Oral




Primary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Until subject discontinuation (up to 3 years) ]
    PFS is defined as the time from randomization to the earliest objective evidence of radiographic progression, unequivocal clinical progression, or death on study, whichever occurs first


Secondary Outcome Measures :
  1. Time to prostate-specific antigen (PSA) progression [ Time Frame: Until subject discontinuation (up to 5 years) ]
    Time (in months) from randomization to the date of the first PSA value in Period 2 demonstrating progression (Period 2)

  2. PSA response [ Time Frame: Until subject discontinuation (up to 5 years) ]
    Percentage change in PSA from randomization to Week 13 (or earlier for those that discontinue therapy), as well as the maximum decline in PSA that occurs at any point after treatment

  3. Objective response rate [ Time Frame: Until subject discontinuation (up to 5 years) ]
    Best overall radiographic response after randomization as per the Investigator assessments of response for soft tissue disease per RECIST 1.1, in subjects who have a measurable tumor

  4. Time to pain progression [ Time Frame: Until subject discontinuation (up to 5 years) ]
    Time (in months) to an increase of >= 30% from randomization in the mean of Brief Pain Inventory Short Form (BPI-SF) pain intensity item scores

  5. Time to opiate use for cancer-related pain [ Time Frame: Until subject discontinuation (up to 5 years) ]
    Time (in months) to initiation of chronic administration of opiate analgesia

  6. Time to first skeletal-related event (SRE) [ Time Frame: Until subject discontinuation (up to 5 years) ]
    Time (in months) from randomization to radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain

  7. Quality of life as assessed Functional Assessment of Cancer Therapy - Prostate (FACT-P) [ Time Frame: Until subject discontinuation (up to 5 years) ]
    The FACT-P quality of life questionnaire is a multi-dimensional, self-reported quality of life instrument specifically designed for use with prostate cancer patients. It consists of 27 core items which assess patient function in four domains: physical, social/family, emotional, and functional well-being, which is further supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score with higher scores representing better quality of life.

  8. Quality of life assessed using EuroQol 5 dimension, 5 level health state utility index (EQ-5D-5L) [ Time Frame: Until subject discontinuation (up to 5 years) ]
    EQ-5D-5L is designed for self-completion by respondents. It consists of 2 pages comprising the following five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels and the subject is asked to indicate his health state by ticking the box with the most appropriate statement.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
  • Ongoing androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of initiation of investigational medicinal product (IMP), or bilateral orchiectomy (i.e., surgical or medical castration);
  • Metastatic disease documented by at least 2 bone lesions on bone scan, or soft tissue disease documented by computed tomography (CT)/magnetic resonance imaging (MRI);
  • Progressive disease at study entry defined as the following occurring in the setting of castrate levels of testosterone: Prostate specific antigen (PSA) progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination.
  • Asymptomatic or minimally symptomatic prostate cancer (Brief Pain Inventory - Short Form (BPI-SF) question 3 score of < 4);
  • Eastern Cooperative Oncology Group (ECOG) performance score of 0-1;
  • Estimated life expectancy of ≥ 12 months;
  • Be suitable and willing to receive chemotherapy as part of the trial;
  • Able to swallow the IMP and comply with study requirements;
  • Subject agrees not to participate in another interventional study while on treatment.

Exclusion Criteria:

  • Prior treatment with the following agents for the treatment of prostate cancer: Aminoglutethimide; Ketoconazole; Abiraterone; Enzalutamide or participation in a clinical trial of enzalutamide; 223Ra, 89Sr, 153Sm, 186Re/188Re; Immunomodulatory therapies; Cytotoxic chemotherapy; Participation in a clinical trial of an investigational agent that inhibits the AR or androgen synthesis unless the treatment was placebo;
  • Current or prior treatment within 4 weeks prior to initiation of IMP with the following agents for the treatment of prostate cancer: Antiandrogens; 5-α reductase inhibitors; Estrogens; Anabolic steroids; Drugs with antiandrogenic properties; Progestational agents;
  • Subject has received investigational therapy within 28 days or 5 half-lives whichever is longer, prior to initiation of IMP;
  • Use of opiate analgesia for pain from prostate cancer within 4 weeks prior to initiation of IMP;
  • Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to initiation of IMP;
  • Major surgery within 4 weeks prior to initiation of IMP;
  • History of seizure or any condition that may predispose to seizures at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months prior to Screening;
  • Known or suspected brain metastasis or active leptomeningeal disease;
  • History of another malignancy within the previous 5 years other than non-melanoma skin cancer;
  • Clinically significant cardiovascular disease;
  • Gastrointestinal disorders affecting absorption;
  • Medical contraindications to the use of prednisolone or docetaxel;
  • Allergies to any of the active ingredients or excipients in the study drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02288247


Locations
Show Show 89 study locations
Sponsors and Collaborators
Astellas Pharma Europe Ltd.
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators
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Study Director: Medical Director Astellas Pharma Europe Ltd.
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Responsible Party: Astellas Pharma Europe Ltd.
ClinicalTrials.gov Identifier: NCT02288247    
Other Study ID Numbers: 9785-MA-1001
2013-004711-50 ( EudraCT Number )
First Posted: November 11, 2014    Key Record Dates
Last Update Posted: July 15, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe Ltd. ):
Metastatic
Castration-resistant
Docetaxel
Chemotherapy- Naïve
Enzalutamide
Prostate Cancer
Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer
Prednisolone
Xtandi
Metastatic Castration Resistant Prostate Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Prednisolone
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal