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Trial record 1 of 1 for:    NCT01889238
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Safety and Efficacy Study of Enzalutamide in Patients With Advanced, Androgen Receptor-Positive, Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT01889238
Recruitment Status : Active, not recruiting
First Posted : June 28, 2013
Results First Posted : August 22, 2018
Last Update Posted : April 22, 2020
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE June 26, 2013
First Posted Date  ICMJE June 28, 2013
Results First Submitted Date  ICMJE July 26, 2018
Results First Posted Date  ICMJE August 22, 2018
Last Update Posted Date April 22, 2020
Actual Study Start Date  ICMJE June 12, 2013
Actual Primary Completion Date March 1, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2018)
  • Percentage of Participants With Clinical Benefit at Week 16: Evaluable Population [ Time Frame: Week 16 ]
    Percentage of participants with a clinical benefit at Week 16 defined as percentage of participants with a best response of complete response (CR), partial response(PR), stable disease(SD) for >= 16 weeks on radiologic imaging based on Investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1(RECIST 1.1). An estimate of the percentage and its exact 2-sided 85% confidence interval(CI) were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10mm short axis. PR: At least 30% decrease in sum of longest diameter (LD) of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference
  • Percentage of Participants With Clinical Benefit at Week 16: Intent-to-Treat (ITT) Population [ Time Frame: Week 16 ]
    Percentage of participants with a clinical benefit at Week 16 defined as percentage of participants with a best response of CR, PR, or SD for >= 16 weeks on radiologic imaging based on Investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference.
Original Primary Outcome Measures  ICMJE
 (submitted: June 26, 2013)
Clinical Benefit Rate [ Time Frame: ≥ 16 weeks ]
To determine clinical benefit rate, defined as the proportion of evaluable patients with androgen receptor positive (AR+), triple negative breast cancer (TNBC) with a best response of complete response (CR), partial response (PR), or stable disease (SD) ≥ 16 weeks.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2018)
  • Percentage of Participants With Clinical Benefit at Week 24: Evaluable Population [ Time Frame: Week 24 ]
    Percentage of participants with a clinical benefit at Week 24 defined as percentage of participants with a best response of CR, PR, or SD for >= 24 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference.
  • Percentage of Participants With Clinical Benefit at Week 24: ITT Population [ Time Frame: Week 24 ]
    Percentage of participants with a clinical benefit at Week 24 defined as percentage of participants with a best response of CR, PR, or SD for >= 24 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference.
  • Percentage of Participants With Best Objective Response: Evaluable Population [ Time Frame: From Baseline up to disease progression or death due to any cause (up to 87 Weeks) ]
    Percentage of participants with best objective response defined as percentage of participants with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions.
  • Percentage of Participants With Best Objective Response: ITT Population [ Time Frame: From Baseline up to disease progression or death due to any cause (up to 87 Weeks) ]
    Percentage of participants with best objective response defined as percentage of participants with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions.
  • Progression-Free Survival (PFS): Evaluable Population [ Time Frame: From Baseline up to disease progression or death due to any cause (up to 87 Weeks) ]
    PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.
  • Progression-Free Survival: ITT Population [ Time Frame: From Baseline up to disease progression or death due to any cause (up to 87 Weeks) ]
    PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2013)
  • Clinical Benefit Rate [ Time Frame: ≥ 24 weeks ]
    To determine clinical benefit rate, defined as the proportion of evaluable patients with a best response of Complete Response, Partial Response, or Stable Disease ≥ 24 weeks;
  • Best Objective Response Rate [ Time Frame: ≥ 16 weeks ]
  • Duration of Response [ Time Frame: ≥ 16 weeks ]
  • Time to Response [ Time Frame: ≥ 16 weeks ]
  • Progression Free Survival (PFS) [ Time Frame: ≥ 16 weeks ]
  • Pharmacokinetics - Ctrough [ Time Frame: ≥ 16 weeks ]
    To assess the pharmacokinetics (PK) of enzalutamide and its active metabolite N desmethyl enzalutamide
Current Other Pre-specified Outcome Measures
 (submitted: July 26, 2018)
  • Trough Plasma Concentration of Enzalutamide and Its Metabolite, [ Time Frame: Predose on Day 1 (Baseline), Week 9 and Week 17 ]
    M2 was the metabolite of enzalutamide. The lower limit of quantitation (LLQ) was 0.0200 micrograms per milliliter (mcg/ml) for enzalutamide and M2.
  • Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 87 weeks ]
    An AEs was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent are events between first dose of study drug and up to 87 weeks that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.
  • Number of Participants With Study Drug Discontinuation Due to Adverse Events [ Time Frame: Baseline up to 87 weeks ]
  • Number of Participants With Grade 3 or Higher Adverse Events [ Time Frame: Baseline up to 87 weeks ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. As per the NCI CTCAE, version 4.0, Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death. Only the participants with treatment-emergent AEs of Grade 3 (severe) or higher grade were reported in this outcome measure.
  • Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Baseline up to 87 weeks ]
    Criteria: Systolic blood pressure (SBP):absolute SBP<90 millimeters of mercury (mmHg) and decrease from baseline (DFB)>30mmHg, absolute SBP>180mmHg and increase from baseline (IFB)>40 mmHg, final visit or 2 consecutive visits SBP>=20 mmHg change from baseline (CFB), most extreme post-baseline SBP>=140mmHg, most extreme post- baseline SBP>=180mmHg, most extreme SBP>=140mmHg and>=20 mmHg CFB, most extreme SBP>=180mmHg and>=20mmHg CFB; diastolic blood pressure (DBP): absolute DBP>105mmHg and IFB>30mmHg, absolute DBP<50mmHg and DFB>20mmHg, final visit or 2 consecutive visits DBP>=15mmHg CFB, most extreme post-baseline DBP>=90mmHg, most extreme post-baseline DBP>=105mmHg, most extreme DBP>=90mmHg and>=15mmHg CFB, most extreme DBP>=105mmHg and>=15mmHg CFB; heart rate<50beats per minute (BPM) and DFB>20BPM or heart rate>120BPM and IFB>30BPM. Only those categories, in which at least 1 subject had data were reported.
  • Number of Participants With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades [ Time Frame: Baseline up to 87 weeks ]
    Laboratory tests included hematology parameters (low lymphocytes, WBC, neutrophils, hemoglobin and platelets) and chemistry parameters (mean albumin, Blood urea nitrogen [BUN], calcium, Lactate dehydrogenase [LDH], alanine aminotransferase, Aspartate aminotransferase , bilirubin, Alkaline phosphatase, creatinine and glucose). Number of participants with change from baseline in laboratory parameters Grades by 2 or More Grades as per National Cancer Institute Common Terminology Criteria (NCI CTC) (Grade 0= within normal limits, Grade 1=Mild, Grade 2=Moderate, Grade 3= Severe, Grade 4= Life-threatening) were reported.
Original Other Pre-specified Outcome Measures
 (submitted: June 26, 2013)
  • Overall Survival (OS) [ Time Frame: ≥ 16 weeks ]
  • Androgen Receptor Expression [ Time Frame: ≥ 16 weeks ]
    To determine the extent of androgen receptor (AR) expression and signaling in breast tissue and to evaluate the relationship of this expression with enzalutamide effects on circulating tumor biomarkers, circulating hormones, and clinical outcomes.
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Enzalutamide in Patients With Advanced, Androgen Receptor-Positive, Triple Negative Breast Cancer
Official Title  ICMJE A PHASE 2, SINGLE-ARM, OPEN-LABEL, MULTICENTER STUDY OF THE CLINICAL ACTIVITY AND SAFETY OF ENZALUTAMIDE IN PATIENTS WITH ADVANCED, ANDROGEN RECEPTOR-POSITIVE, TRIPLE-NEGATIVE BREAST CANCER
Brief Summary The purpose of this study is to determine if enzalutamide is safe and effective in the treatment of patients with advanced breast cancer that express the androgen receptor but do not express the estrogen or progesterone receptor and are not Her2 amplified.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced, Androgen Receptor Positive Triple Negative Breast Cancer
Intervention  ICMJE Drug: Enzalutamide
160 mg administered as four soft gelatin capsules orally once daily
Other Names:
  • Xtandi®
  • MDV3100
Study Arms  ICMJE Experimental: Enzalutamide
160 mg administered as four 40 mg soft gelatin capsules orally once daily
Intervention: Drug: Enzalutamide
Publications * Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, Nanda R, Gucalp A, Awada A, Garcia-Estevez L, Trudeau ME, Steinberg J, Uppal H, Tudor IC, Peterson A, Cortes J. Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer. J Clin Oncol. 2018 Mar 20;36(9):884-890. doi: 10.1200/JCO.2016.71.3495. Epub 2018 Jan 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 7, 2015)
118
Original Estimated Enrollment  ICMJE
 (submitted: June 26, 2013)
80
Estimated Study Completion Date  ICMJE March 31, 2021
Actual Primary Completion Date March 1, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Women at least 18 years of age;
  • Advanced AR+ TNBC;
  • Availability of a representative tumor specimen:
  • Either measurable disease or bone only nonmeasurable disease;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

  • Any severe concurrent disease, infection, or comorbid condition;
  • Any condition or reason that interferes with the patient's ability to participate in the trial, that may cause undue risk, or complicates the interpretation of safety data;
  • Current or previously treated brain metastasis or active leptomeningeal disease;
  • Current hormone replacement therapy;
  • Local palliative radiation therapy within 7 days before day 1;
  • History of another invasive cancer within 5 years of day 1;
  • Absolute neutrophil count < 1500/µL, platelet count < 75,000/µL, or hemoglobin < 9 g/dL (5.6 mmol/L) at the screening visit;
  • Creatinine > 1.5 times upper limit of normal (ULN) at the screening visit;
  • History of seizure or any condition that may predispose to seizure;
  • Clinically significant cardiovascular disease;
  • Active gastrointestinal disorder affecting absorption;
  • Major surgery within 4 weeks before day 1;
  • Treatment with any commercially available anticancer agent within 14 days before day 1;
  • Treatment with any investigational agent within 2 weeks before day 1;
  • Treatment with any of the following medications within 2 weeks before day 1: Estrogens, including hormone replacement therapy; Androgens (testosterone, dihydroepiandrosterone, etc);Systemic radionuclides (eg, samarium or strontium);Vaccine therapy;
  • Hypoglycemic episode requiring medical intervention while on insulin treatment within 12 months before day 1;
  • Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Ireland,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01889238
Other Study ID Numbers  ICMJE MDV3100-11
2013-000698-57 ( EudraCT Number )
C3431007 ( Other Identifier: Alias Study Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE
  • Astellas Pharma Inc
  • Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
Study Chair: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP