Clinical Trials/NCT02929576

NCT02929576

Withdrawn

Phase 3

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

Pfizer0 sitesSeptember 2016

ConditionsBreast Cancer

InterventionsEnzalutamide Paclitaxel Placebo

DrugsPlacebo Enzalutamide Paclitaxel

Overview

Phase: Phase 3
Intervention: Enzalutamide
Conditions: Breast Cancer
Sponsor: Pfizer
Primary Endpoint: Progression Free Survival (PFS)
Status: Withdrawn
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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).

Registry

clinicaltrials.gov

Start Date

September 2016

End Date

April 2019

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Pfizer

Responsible Party

Sponsor

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.

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)

Arms & Interventions

Double-blind enzalutamide with paclitaxel

Intervention: Enzalutamide

Double-blind enzalutamide with paclitaxel

Intervention: Paclitaxel

Double-blind placebo with paclitaxel

Intervention: Placebo

Double-blind placebo with paclitaxel

Intervention: Paclitaxel

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.

Intervention: Enzalutamide

Open-label enzalutamide monotherapy followed by paclitaxel

Intervention: Paclitaxel

Outcomes

Primary Outcomes

Progression Free Survival (PFS)

Time Frame: Anticipated in about 31 months following first patient enrolled

Secondary Outcomes

PFS assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1(Anticipated in about 31 months following first patient enrolled)
Time to treatment failure(Anticipated in about 31 months following first patient enrolled)
Overall survival(Anticipated in about 40 months following first patient enrolled)
Best overall response(Anticipated in about 31 months following first patient enrolled)
Duration of response(Anticipated in about 31 months following first patient enrolled)
Time to second disease progression in patients randomly assigned to enzalutamide monotherapy who subsequently receive paclitaxel(Anticipated in about 31 months following first patient enrolled)
Clinical benefit rate at 24 weeks (CBR24): From the start of treatment D1 assessed every 8 weeks +/- 1 week while on study treatment(24 weeks)
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(Anticipated in about 31 months following first patient enrolled)
Time to functional status deterioration using the Functional Assessment of Cancer Therapy-Breast (FACT-B) trial outcome index (physical, functional, breast) (TOI-PFB)(Anticipated in about 31 months following first patient enrolled)
Pharmacokinetics of enzalutamide as assessed by trough plasma concentrations(Anticipated in about 31 months following first patient enrolled)
Pharmacokinetics of the active metabolite N-desmethyl enzalutamide as assessed by trough plasma concentrations(Anticipated in about 31 months following first patient enrolled)