Single Arm, Phase IIA Clinical Trial Assessing The Safety And Efficacy of Atezolizumab in Combination With Paclitaxel, Trastuzumab, and Pertuzumab in Patients With Metastatic HER-2 Positive Breast Cancer

Fox Chase Cancer Center1 site in 1 country16 target enrollmentJune 13, 2017

ConditionsHER2-positive Breast Cancer

InterventionsAtezolizumab Paclitaxel Trastuzumab Pertuzumab

Overview

Phase: Phase 2
Intervention: Atezolizumab
Conditions: HER2-positive Breast Cancer
Sponsor: Fox Chase Cancer Center
Enrollment: 16
Locations: 1
Primary Endpoint: Number of participants with treatment-related adverse events
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single arm, Phase IIA clinical trial assessing the safety and efficacy of atezolizumab in combination with paclitaxel, trastuzumab, and pertuzumab in 50 patients with locally advanced, unresectable, or metastatic HER2-overexpressing breast cancer. Due to concerns that corticosteroids may have a negative effect on tumor immunity expected with addition of atezolizumab to the standard of care regimen, patients will receive premedication with dexamethasone only for weeks 1 and 2 of the weekly paclitaxel, and then corticosteroid premedication will be discontinued subsequently.

Patients must have pathologically confirmed HER2-overexpressing breast cancer that is locally recurrent, unresectable, or metastatic, with measurable disease as defined by RECIST v1.1. Tumor measurements and bone scans will be performed every 9 weeks while patients are on study.

Registry

clinicaltrials.gov

Start Date

June 13, 2017

End Date

December 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Fox Chase Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Women diagnosed with pathologically confirmed HER2-overexpressing breast cancer, that is locally recurrent, unresectable or metastatic (negative or positive for ER/PR, and positive for HER2).
•HER2 status confirmed positive by means of immunohistochemistry (IHC) or in situ hybridization (ISH) according to ASCO/CAP 2013 guidelines. It is considered positive if scored as 3+ by an IHC method defined as uniform membrane staining for HER2 in 10% or more of tumor cells or demonstrate HER2 gene amplification by an ISH method (single probe, average HER2 copy number ≥ 6.0 signals/cell; dual probe HER2/CEP17 ratio ≥2.0 with an average HER2 copy number ≥4.0 signals/cell; dual probe HER2/chromosome enumeration probe (CEP)17 ratio ≥2.0 with an average HER2 copy number \<4.0 signals/cell; HER2/CEP17 ratio \<2.0 with an average HER2 copy number ≥ 6.0 signals/cell).
•Have measurable clinical disease: Measurable disease, defined as at least 1 measurable lesion on a CT scan as defined by RECIST (version v1.1).
•Age \> 18 years.
•ECOG performance status 0,1or
•Adequate organ function (defined by the following parameters): Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. Hemoglobin ≥ 10 g/dL.Platelets ≥ 100 x 109/L. Serum bilirubin ≤ 1.5 x upper normal limit (UNL), except patients with Gilbert's syndrome. Serum alanine aminotransferase (ALT) ≤ 2 x UNL or ≤ 5.0 x UNL in case of liver metastases. Serum aspartate aminotransferase (AST) ≤ 2 x UNL or ≤ 5.0 x UNL in case of liver metastases. Serum creatinine \< 140 μmol/L (\< 1.6 mg/dL) or 1.5x the upper limit of normal, whichever is less. Serum alkaline phosphatase (ALP) ≤ UNL or ≤ 2.5 x ULN in case of liver and bone metastases.
•Left ventricular ejection fraction of 50% or more at baseline (by echocardiography or multiple-gated acquisition scanning).
•Patients may have received one prior hormonal treatment for metastatic disease.
•Patients may have received adjuvant or neoadjuvant chemotherapy with or without trastuzumab and pertuzumab with an interval greater than than 12 months since completion of adjuvant/neoadjuvant treatment.
•Ability to understand and willingness to sign a written informed consent and HIPAA consent document.

Exclusion Criteria

•Patients participating in another trial of an investigational agent within 4 weeks of the 1st dose of the study.
•Patients with tumors that cannot be measured or clinically followed.
•Patients who had received therapy for metastatic breast cancer (other than that described above).
•Patients with active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 4 weeks prior to trial treatment.
•Patients with any baseline grade 2 neuropathy.
•Patients with known prior hypersensitivity reaction to any of the study drugs.
•Active autoimmune disease that is requiring systemic treatment within the past 3 months or documented history of clinically active autoimmune disease that requires systemic corticosteroids or immunosuppressive therapy.
•Diagnosis of immunosuppression or receiving steroid therapy or other immunosuppressive therapy within 4 weeks of the study.
•Have evidence of interstitial lung disease or active, non-infectious pneumonitis.
•Patients with human immunodeficiency virus (HIV1/2). An HIV test must be performed to confirm status prior to enrollment.

Arms & Interventions

Investigational Arm

Intervention: Atezolizumab

Investigational Arm

Intervention: Paclitaxel

Investigational Arm

Intervention: Trastuzumab

Investigational Arm

Intervention: Pertuzumab

Outcomes

Primary Outcomes

Number of participants with treatment-related adverse events

Time Frame: Up to 5 years after stopping study treatment

Treatment-related adverse events will be assessed by CTCAE v4.0

Antitumor activity of atezolizumab plus the standard regimen of paclitaxel, trastuzumab, and pertuzumab

Time Frame: An average of 18 weeks

Antitumor activity will be measured by RECIST v1.1

Secondary Outcomes

Overall survival (OS)(Up to 5 years after the last patient stops treatment)
Time to tumor progression (TTP)(Up to 5 years after the last patient stops treatment)
Time to treatment failure (TTF)(Up to 5 years after the last patient stops treatment)
Progression free survival (PFS)(Up to 5 years after the last patient stops treatment)
Clinical benefit rate (CBR)(Up to 5 years after the last patient stops treatment)
Duration of response (DOR)(Up to 5 years after the last patient stops treatment)
Correlation of biomarkers related to PD-L1 blockade with objective response rate (ORR), CBR, PFS, OS, and DOR.(Up to 5 years after the last patient stops treatment)
Efficacy according to hormone receptor status (ER/PR)(Up to 5 years after the last patient stops treatment)
Feasibility of discontinuation of corticosteroids use after 2 weekly doses of paclitaxel(Up to 5 years after the last patient stops treatment)
Rate of occurrence of paclitaxel-related infusion hypersensitivity reaction after discontinuation of corticosteroids(An average of 18 weeks)
Cardiac safety(An average of 18 weeks)