Clinical trial NCT02929576: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: metastatic
triple negative
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
name: Medivation, Inc.
First posted: 2016-10-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Anticipated in about 31 months following first patient enrolled
Secondary outcomes:
measure: Overall survival
timeFrame: Anticipated in about 40 months following first patient enrolled
measure: PFS assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
timeFrame: Anticipated in about 31 months following first patient enrolled
measure: Time to treatment failure
timeFrame: Anticipated in about 31 months following first patient enrolled
measure: Best overall response
timeFrame: Anticipated in about 31 months following first patient enrolled
measure: Duration of response
timeFrame: Anticipated in about 31 months following first patient enrolled
measure: Time to second disease progression in patients randomly assigned to enzalutamide monotherapy who subsequently receive paclitaxel
timeFrame: Anticipated in about 31 months following first patient enrolled
measure: Clinical benefit rate at 24 weeks (CBR24): From the start of treatment D1 assessed every 8 weeks +/- 1 week while on study treatment
timeFrame: 24 weeks
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
timeFrame: Anticipated in about 31 months following first patient enrolled
measure: Time to functional status deterioration using the Functional Assessment of Cancer Therapy-Breast (FACT-B) trial outcome index (physical, functional, breast) (TOI-PFB)
timeFrame: Anticipated in about 31 months following first patient enrolled
measure: Pharmacokinetics of enzalutamide as assessed by trough plasma concentrations
timeFrame: Anticipated in about 31 months following first patient enrolled
measure: Pharmacokinetics of the active metabolite N-desmethyl enzalutamide as assessed by trough plasma concentrations
timeFrame: Anticipated in about 31 months following first patient enrolled
Other outcomes:
Locations:
city: Topeka
country: United States
state: Kansas
city: Metairie
country: United States
state: Louisiana
city: Bronx
country: United States
state: New York
city: Houston
country: United States
state: Texas
city: Tacoma
country: United States
state: Washington
city: Wenatchee
country: United States
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: