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Trial record 5 of 106 for:    mdv3100 | Open Studies

Efficacy and Safety Study of Enzalutamide in Combination With Paclitaxel Chemotherapy or as Monotherapy Versus Placebo With Paclitaxel in Patients With Advanced, Diagnostic-Positive, Triple-Negative Breast Cancer (ENDEAR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Medivation, Inc.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Medivation, Inc.
ClinicalTrials.gov Identifier:
NCT02929576
First received: September 7, 2016
Last updated: October 7, 2016
Last verified: October 2016
  Purpose
The purpose of this study is to evaluate and compare the clinical benefit and safety of treatment with enzalutamide in combination with paclitaxel chemotherapy or as monotherapy versus placebo with paclitaxel in patients with locally advanced or metastatic, diagnostic-positive, triple-negative breast cancer (TNBC).

Condition Intervention Phase
Breast Cancer
Drug: Enzalutamide
Drug: Placebo
Drug: Paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, International Study Comparing the Efficacy and Safety of Enzalutamide in Combination With Paclitaxel Chemotherapy or as Monotherapy Versus Placebo With Paclitaxel in Patients With Advanced, Diagnostic-Positive, Triple-Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Medivation, Inc.:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Anticipated in about 40 months following first patient enrolled ] [ Designated as safety issue: No ]
  • PFS assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Best overall response [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]
    Best overall response is defined as the best tumor response (complete response [CR], partial response [PR], stable disease, progressive disease, not evaluable) based on investigator assessment per RECIST 1.1 over all tumor assessments performed any time on study. Best objective response rate is defined as the proportion of patients with a best overall response of CR or PR for all patients based on investigator assessment per RECIST 1.1. The 2-sided 95% Confidence Interval (CI) will be reported for each treatment group using the Clopper-Pearson method.

  • Duration of response [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Time to second disease progression in patients randomly assigned to enzalutamide monotherapy who subsequently receive paclitaxel [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Clinical benefit rate at 24 weeks (CBR24): From the start of treatment D1 assessed every 8 weeks +/- 1 week while on study treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    CBR (complete, partial response, or stable disease lasting 24 weeks or longer) assessed per RECIST 1.1

  • Safety as assessed by percentage of patients with any Adverse Event (AE), AE leading to Study Drug Discontinuation, AE leading to death, Serious Adverse Event (SAE), AE related to study drug, SAE related to study drug [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: Yes ]
  • Time to functional status deterioration using the Functional Assessment of Cancer Therapy-Breast (FACT-B) trial outcome index (physical, functional, breast) (TOI-PFB) [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Pharmacokinetics of enzalutamide as assessed by trough plasma concentrations [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]
  • Pharmacokinetics of the active metabolite N-desmethyl enzalutamide as assessed by trough plasma concentrations [ Time Frame: Anticipated in about 31 months following first patient enrolled ] [ Designated as safety issue: No ]

Estimated Enrollment: 780
Study Start Date: September 2016
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Double-blind enzalutamide with paclitaxel Drug: Enzalutamide
Enzalutamide will be administered as four 40-mg capsules once daily (160 mg/day).
Other Names:
  • Xtandi
  • MDV3100
Drug: Paclitaxel
Paclitaxel (90 mg/m2) will be administered by constant-rate intravenous infusion of ≤ 1 hour once weekly for 16 weeks. Dose reductions or alterations to the schedule are allowed to maintain patient safety.
Placebo Comparator: Double-blind placebo with paclitaxel Drug: Placebo Drug: Paclitaxel
Paclitaxel (90 mg/m2) will be administered by constant-rate intravenous infusion of ≤ 1 hour once weekly for 16 weeks. Dose reductions or alterations to the schedule are allowed to maintain patient safety.
Experimental: Open-label enzalutamide monotherapy followed by paclitaxel
At the time of disease progression, enzalutamide treatment will be discontinued and paclitaxel will be administered if considered to be an appropriate treatment by the treating physician until second disease progression.
Drug: Enzalutamide
Enzalutamide will be administered as four 40-mg capsules once daily (160 mg/day).
Other Names:
  • Xtandi
  • MDV3100
Drug: Paclitaxel
Paclitaxel (90 mg/m2) will be administered by constant-rate intravenous infusion of ≤ 1 hour once weekly for 16 weeks. Dose reductions or alterations to the schedule are allowed to maintain patient safety.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult women and men at least 18 years of age and willing and able to provide informed consent.
  • Has advanced TNBC:
  • TNBC is defined as staining by immunohistochemistry (IHC) < 1% or Allred score < 2 for estrogen receptor (ER) and progesterone receptor (PgR), and 0 or 1+ by IHC for human epidermal growth factor receptor 2 (HER2) or negative for gene amplification (average HER2 copy number < 4 signals/cell; HER2:CEP17 ratio < 2.0).
  • Advanced disease is defined as locally advanced or metastatic disease not amenable to curative intent surgery or radiotherapy.
  • Has diagnostic-positive status as determined by a central diagnostic testing laboratory.
  • Received 0 or 1 prior line of systemic therapy in the advanced disease setting.
  • Patients who received 1 prior line of therapy for locally advanced or metastatic TNBC must have objective disease progression as assessed by the investigator.
  • Has measurable and/or disease that is not measurable but is evaluable using RECIST 1.1 (eg, bone metastases, pathologic lymph nodes, or skin lesions).
  • Patients with nonmeasurable and nonevaluable TNBC (eg, malignant effusions or bone marrow as the only manifestations of disease) are not eligible for enrollment.
  • Patients with metastatic disease limited to the bone must have disease adequately visualized by computed tomography (CT) with bone windows, magnetic resonance imaging (MRI), or x-ray.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 at screening and a life expectancy of at least 3 months from randomization.

Exclusion Criteria:

  • Received a taxane regimen ≥ 28 days in duration in the advanced disease setting.
  • Prior taxane therapy for neoadjuvant and/or adjuvant disease is permitted.
  • A single dose of a taxane given as part of an every-3-weeks regimen is permitted.
  • Two doses of a taxane given as part of a once-weekly regimen is permitted.
  • Had a disease-free interval of ≤ 12 months from the last dose of taxane when used as part of adjuvant therapy for patients who did not receive prior therapy for locally advanced or metastatic breast cancer.
  • Has history of or known central nervous system (CNS) metastasis or active leptomeningeal disease; brain imaging is required for all patients during screening.
  • Received any anticancer agent (commercially available or investigational) within 14 days before randomization.
  • Received treatment with any of the following medications within 14 days before randomization:
  • Estrogens, including hormone replacement therapy
  • Androgens (eg, testosterone, dehydroepiandrosterone)
  • Systemic radionuclides (eg, samarium, strontium)
  • Had major surgery within 4 weeks before randomization.
  • Has a history of another invasive cancer within 3 years before randomization, with the exception of fully treated cancers with a remote probability of recurrence.
  • Has a history of a seizure condition or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma).
  • Has known hypersensitivity to any of the enzalutamide/placebo capsule components.
  • Had a hypersensitivity reaction to Cremophor EL (polyoxyethylated castor oil) or a drug formulated in Cremophor EL, such as paclitaxel, unless successfully treated and rechallenged with appropriate premedications.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02929576

Contacts
Contact: Medivation Clinical Operations +1 (415) 543-3470 BrCa20@Medivation.com
Contact: Medivation Clinical Trial Disclosure TrialDisclosure@Medivation.com

Locations
United States, Kansas
Recruiting
Topeka, Kansas, United States, 66606
United States, Louisiana
Recruiting
Metairie, Louisiana, United States, 70006
United States, New York
Recruiting
Bronx, New York, United States, 10469
United States, Texas
Recruiting
Houston, Texas, United States, 77030
United States, Washington
Recruiting
Tacoma, Washington, United States, 98405
Recruiting
Wenatchee, Washington, United States, 98801
Sponsors and Collaborators
Medivation, Inc.
Astellas Pharma Inc
Investigators
Study Director: Medical Director Medivation, Inc.
  More Information

Responsible Party: Medivation, Inc.
ClinicalTrials.gov Identifier: NCT02929576     History of Changes
Other Study ID Numbers: MDV3100-20  2016-000796-25 
Study First Received: September 7, 2016
Last Updated: October 7, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Medivation, Inc.:
metastatic
triple negative

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016