Clinical Trials /

Clinical Trial of Atezolizumab With Paclitaxel, Trastuzumab, and Pertuzumab in Patients With Metastatic HER-2 Positive Breast Cancer

NCT03125928

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial of Atezolizumab With Paclitaxel, Trastuzumab, and Pertuzumab in Patients With Metastatic HER-2 Positive Breast Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BR-093
  • SECONDARY ID: 17-1010
  • NCT ID: NCT03125928

Conditions

  • HER2-positive Breast Cancer

Interventions

DrugSynonymsArms
AtezolizumabInvestigational Arm
PaclitaxelInvestigational Arm
TrastuzumabInvestigational Arm
PertuzumabInvestigational Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Investigational ArmExperimental
  • Atezolizumab
  • Paclitaxel
  • Trastuzumab
  • Pertuzumab

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 2.

          -  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.

          -  Female participants of childbearing age must be willing to use contraception methods,
             or abstain from sexual activity throughout the course of the study and for 7 months
             after the last dose of atezolizumab.

          -  Have provided tissue from a newly obtained biopsy obtained from a focus of metastatic
             disease, and be willing to consider repeat biopsy post-treatment after at least 4
             cycles of treatment (an archival tissue sample may be substituted if new biopsy
             cannot be obtained and by discretion of Sponsor Investigator).

        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.

          -  Patients who are carriers of hepatitis virus B and C. Hepatitis B and C testing must
             be performed to confirm status prior to enrollment.

          -  Prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed cell death
             1 ligand (PDL-1), anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte
             -associated antigen-4 (CTLA-4) antibody.

          -  Pregnant, breastfeeding, or expecting to conceive within the projected time of the
             trial, starting with the pre-screening or screening visit and through 7 months after
             the last dose of trial treatment.

          -  Active infection requiring systemic therapy.

          -  Active substance abuse or psychiatric disorders.

          -  The use of a RANKL inhibitor (denosumab) must be discontinued during the study.
             Bisphosphonate therapy is permitted.

          -  The following treatments must be discontinued: Herbal Medications. Immunomodulatory
             agents, including but not limited to interferons or IL-2. Immunosuppressive
             medications, including but not limited to cyclophosphamide, azathioprine,
             methotrexate, and thalidomide. Systemic corticosteroids. Anti−TNF-α agents.

          -  Any live, attenuated vaccine within 28 days prior to the first day of treatment or
             during study treatment, or unwillingness to avoid live, attenuated vaccines within 90
             days following the last dose of atezolizumab.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events
Time Frame:Up to 5 years after stopping study treatment
Safety Issue:
Description:Treatment-related adverse events will be assessed by CTCAE v4.0

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:OS is defined as the time from initiation of treatment until death from any cause or end of the study period, whichever occurs first.
Measure:Time to tumor progression (TTP)
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:TTP is defined as the duration of time from the start of treatment to the first objectively documented instance of progressive disease.
Measure:Time to treatment failure (TTF)
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:TTF is defined as the duration of time from start of treatment to discontinuation of study treatment for reasons defined in the protocol.
Measure:Progression free survival (PFS)
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Measure:Clinical benefit rate (CBR)
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:CBR is defined as the rates of complete response (CR), partial response (PR) and stable disease (SD).
Measure:Duration of response (DOR)
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:Per RECIST v1.1, DOR will be assessed by the duration of overall response, duration fo CR/PR, and duration of SD.
Measure:Correlation of biomarkers related to PD-L1 blockade with objective response rate (ORR), CBR, PFS, OS, and DOR.
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:Efficacy will be assessed according to tumor PD-L1 expression level and tumor infiltrating lymphocytes PD-L1 expression levels.
Measure:Efficacy according to hormone receptor status (ER/PR)
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:This will be a future subset analysis.
Measure:Feasibility of discontinuation of corticosteroids use after 2 weekly doses of paclitaxel
Time Frame:Up to 5 years after the last patient stops treatment
Safety Issue:
Description:This will be assessed by CTCAE v4.0.
Measure:Rate of occurrence of paclitaxel-related infusion hypersensitivity reaction after discontinuation of corticosteroids
Time Frame:An average of 18 weeks
Safety Issue:
Description:This will be assessed by CTCAE v4.0.
Measure:Cardiac safety
Time Frame:An average of 18 weeks
Safety Issue:
Description:Quarterly MUGA or ECHO results assessing occurrence of left ventricular dysfunction.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fox Chase Cancer Center

Trial Keywords

  • Atezolizumab
  • PD-L1

Last Updated

June 7, 2017