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

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ClinicalTrials.gov Identifier: NCT03125928
Recruitment Status : Recruiting
First Posted : April 24, 2017
Last Update Posted : January 20, 2021
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Fox Chase Cancer Center

Tracking Information
First Submitted Date  ICMJE March 22, 2017
First Posted Date  ICMJE April 24, 2017
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE June 13, 2017
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2017)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2017)
  • Overall survival (OS) [ Time Frame: Up to 5 years after the last patient stops treatment ]
    OS is defined as the time from initiation of treatment until death from any cause or end of the study period, whichever occurs first.
  • Time to tumor progression (TTP) [ Time Frame: Up to 5 years after the last patient stops treatment ]
    TTP is defined as the duration of time from the start of treatment to the first objectively documented instance of progressive disease.
  • Time to treatment failure (TTF) [ Time Frame: Up to 5 years after the last patient stops treatment ]
    TTF is defined as the duration of time from start of treatment to discontinuation of study treatment for reasons defined in the protocol.
  • Progression free survival (PFS) [ Time Frame: Up to 5 years after the last patient stops treatment ]
    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
  • Clinical benefit rate (CBR) [ Time Frame: Up to 5 years after the last patient stops treatment ]
    CBR is defined as the rates of complete response (CR), partial response (PR) and stable disease (SD).
  • Duration of response (DOR) [ Time Frame: Up to 5 years after the last patient stops treatment ]
    Per RECIST v1.1, DOR will be assessed by the duration of overall response, duration fo CR/PR, and duration of SD.
  • 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 ]
    Efficacy will be assessed according to tumor PD-L1 expression level and tumor infiltrating lymphocytes PD-L1 expression levels.
  • Efficacy according to hormone receptor status (ER/PR) [ Time Frame: Up to 5 years after the last patient stops treatment ]
    This will be a future subset analysis.
  • Feasibility of discontinuation of corticosteroids use after 2 weekly doses of paclitaxel [ Time Frame: Up to 5 years after the last patient stops treatment ]
    This will be assessed by CTCAE v4.0.
  • Rate of occurrence of paclitaxel-related infusion hypersensitivity reaction after discontinuation of corticosteroids [ Time Frame: An average of 18 weeks ]
    This will be assessed by CTCAE v4.0.
  • Cardiac safety [ Time Frame: An average of 18 weeks ]
    Quarterly MUGA or ECHO results assessing occurrence of left ventricular dysfunction.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial of Atezolizumab With Paclitaxel, Trastuzumab, and Pertuzumab in Patients With Metastatic HER-2 Positive Breast Cancer
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2-positive Breast Cancer
Intervention  ICMJE
  • Drug: Atezolizumab
    Monoclonal antibody
  • Drug: Paclitaxel
    Chemotherapy
  • Drug: Trastuzumab
    Monoclonal antibody
  • Drug: Pertuzumab
    Monoclonal antibody
Study Arms  ICMJE Experimental: Investigational Arm
Interventions:
  • Drug: Atezolizumab
  • Drug: Paclitaxel
  • Drug: Trastuzumab
  • Drug: Pertuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 19, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lori J Goldstein, MD 215-214-1515 lori.goldstein@fccc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03125928
Other Study ID Numbers  ICMJE BR-093
17-1010 ( Other Identifier: Fox Chase Cancer Center IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fox Chase Cancer Center
Study Sponsor  ICMJE Fox Chase Cancer Center
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE Not Provided
PRS Account Fox Chase Cancer Center
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP