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NCT02929576 | Withdrawn Phase 3 DMC

• 2 other identifiers: MDV3100-202016-000796-25
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 6

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

Keywords

metastatic; triple negative

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Anticipated in about 31 months following first patient enrolled

Secondary Outcomes (11)

• Overall survival

  Anticipated in about 40 months following first patient enrolled

• 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

• Best overall response

  Anticipated in about 31 months following first patient enrolled

• Duration of response

  Anticipated in about 31 months following first patient enrolled

Study Arms (3)

Double-blind enzalutamide with paclitaxel

EXPERIMENTAL

Drug: Enzalutamide; Drug: Paclitaxel

Double-blind placebo with paclitaxel

PLACEBO COMPARATOR

Drug: Placebo; Drug: Paclitaxel

Open-label enzalutamide monotherapy followed by paclitaxel

EXPERIMENTAL

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; Drug: Paclitaxel

Interventions

Enzalutamide DRUG

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

Also known as: Xtandi, MDV3100

Double-blind enzalutamide with paclitaxel; Open-label enzalutamide monotherapy followed by paclitaxel

Placebo DRUG

Double-blind placebo with paclitaxel

Paclitaxel 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 enzalutamide with paclitaxel; Double-blind placebo with paclitaxel; Open-label enzalutamide monotherapy followed by paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• Astellas Pharma Inc: collaborator
• Medivation, Inc.: collaborator

Study Sites (6)

Unknown Facility

Topeka, Kansas, 66606, United States

Location

Unknown Facility

Metairie, Louisiana, 70006, United States

Location

Unknown Facility

The Bronx, New York, 10469, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Tacoma, Washington, 98405, United States

Location

Unknown Facility

Wenatchee, Washington, 98801, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

enzalutamide; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: October 11, 2016
• Study Start: September 1, 2016
• Primary Completion: April 1, 2019
• Last Updated: October 22, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)