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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)

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ClinicalTrials.gov Identifier: NCT02288247
Recruitment Status : Active, not recruiting
First Posted : November 11, 2014
Last Update Posted : December 10, 2018
Sponsor:
Collaborator:
Medivation, 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) At Week 13, all subjects will be assessed by prostate-specific antigen (PSA) and imaging. Subjects 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 subjects as long as the investigator considers it to be of clinical benefit (stopping on initiation of any new antineoplastic therapy). Subjects with confirmed PSA response will continue Period 1 until disease progression.

Randomization (Period 2) 274 subjects 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

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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
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : June 2020


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 3 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 3 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 3 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 3 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 3 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 3 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 [ Time Frame: Until subject discontinuation (up to 3 years) ]
    Assessed using Functional Assessment of Cancer Therapy - Prostate (FACT-P) and EuroQol 5 dimension, 5 level health state utility index (EQ-5D-5L)



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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


  Show 89 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe Ltd.
Medivation, 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     History of Changes
Other Study ID Numbers: 9785-MA-1001
2013-004711-50 ( EudraCT Number )
First Posted: November 11, 2014    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018

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
Prostatic Diseases
Genital Diseases, Male
Docetaxel
Prednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone Acetate
Methylprednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
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
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents