Clinical Trials /

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

NCT02929576

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: MDV3100-20
  • SECONDARY ID: 2016-000796-25
  • NCT ID: NCT02929576

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
EnzalutamideXtandi, MDV3100Double-blind enzalutamide with paclitaxel
PlaceboDouble-blind placebo with paclitaxel
PaclitaxelDouble-blind enzalutamide with paclitaxel

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).

Trial Arms

NameTypeDescriptionInterventions
Double-blind enzalutamide with paclitaxelExperimental
  • Enzalutamide
  • Paclitaxel
Double-blind placebo with paclitaxelPlacebo Comparator
  • Placebo
  • Paclitaxel
Open-label enzalutamide monotherapy followed by paclitaxelExperimentalAt 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.
  • Enzalutamide
  • Paclitaxel

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Anticipated in about 31 months following first patient enrolled
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Anticipated in about 40 months following first patient enrolled
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Time to treatment failure
Time Frame:Anticipated in about 31 months following first patient enrolled
Safety Issue:
Description:
Measure:Best overall response
Time Frame:Anticipated in about 31 months following first patient enrolled
Safety Issue:
Description: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.
Measure:Duration of response
Time Frame:Anticipated in about 31 months following first patient enrolled
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:CBR (complete, partial response, or stable disease lasting 24 weeks or longer) assessed per RECIST 1.1
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Pharmacokinetics of enzalutamide as assessed by trough plasma concentrations
Time Frame:Anticipated in about 31 months following first patient enrolled
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Medivation, Inc.

Trial Keywords

  • metastatic
  • triple negative

Last Updated

June 1, 2017