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

NCT ID: NCT02929576

Last Updated: 2018-10-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30

Brief Summary

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).

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Double-blind enzalutamide with paclitaxel

Group Type: EXPERIMENTAL

Enzalutamide

Intervention Type: DRUG

Enzalutamide will be administered as four 40-mg capsules once daily (160 mg/day).

Paclitaxel

Intervention Type: DRUG

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.

Double-blind placebo with paclitaxel

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Enzalutamide

Intervention Type: DRUG

Enzalutamide will be administered as four 40-mg capsules once daily (160 mg/day).

Paclitaxel

Intervention Type: DRUG

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.

Interventions

Enzalutamide

Enzalutamide will be administered as four 40-mg capsules once daily (160 mg/day).

Intervention Type: DRUG

Placebo

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Xtandi; MDV3100

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Medivation, Inc.

INDUSTRY

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Topeka, Kansas, United States

Metairie, Louisiana, United States

The Bronx, New York, United States

Houston, Texas, United States

Tacoma, Washington, United States

Wenatchee, Washington, United States

Countries

United States

Other Identifiers

2016-000796-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MDV3100-20

Identifier Type: -

Identifier Source: org_study_id