Testing the Drug Atezolizumab or Placebo With Usual Therapy in First-Line HER2-Positive Metastatic Breast Cancer

Titre officiel

A Randomized, Double-Blind, Phase III Trial of Paclitaxel/Trastuzumab/Pertuzumab With Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer

Sommaire:

Cet essai de phase III avec répartition aléatoire a pour but d’évaluer l’efficacité du paclitaxel, du trastuzumab et du pertuzumab, avec ou sans atézolizumab, comme traitement du cancer du sein qui s’est propagé à d’autres parties du corps (métastatique). Les médicaments utilisés en chimiothérapie, comme le paclitaxel, agissent de différentes manières pour stopper la croissance des cellules tumorales, soit en tuant les cellules soit en les empêchant de se diviser ou de se propager. Le trastuzumab est une forme de « traitement ciblé », puisqu’il agit en se liant à des molécules particulières (récepteurs) présentes à la surface de cellules cancéreuses connues sous le nom de récepteurs HER2. Lorsque le trastuzumab se fixe aux récepteurs HER2, il bloque les signaux de croissance des cellules cancéreuses. Celles-ci peuvent alors être ciblées par le système immunitaire de l’organisme pour être détruites. Les anticorps monoclonaux, comme le pertuzumab, peuvent nuire à la capacité des cellules cancéreuses de se développer et de se propager. L’immunothérapie par anticorps monoclonaux, comme l’atézolizumab, peut induire des changements dans le système immunitaire de l’organisme et interférer avec la capacité des cellules tumorales à croître et à se propager. On ignore encore si l’administration de paclitaxel, de trastuzumab et de pertuzumab, avec ou sans atézolizumab, peut détruire un plus grand nombre de cellules tumorales.

Description de l'essai

Primary Outcome:

  • Progression free survival
Secondary Outcome:
  • Overall survival
  • Overall objective response
  • Duration of objective response
  • Cumulative incidence of brain metastases
  • Frequency of adverse events, including late immune-related toxicities
PRIMARY OBJECTIVE:
  • To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab, and trastuzumab will improve the progression-free survival (PFS), as assessed by investigator using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria, relative to a regimen of paclitaxel, pertuzumab, trastuzumab, and placebo in patients with newly documented HER2-positive measurable metastatic breast cancer.
SECONDARY OBJECTIVES:
  • To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab, and trastuzumab will improve the overall survival (OS) relative to a regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
  • To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab, and trastuzumab will improve the overall objective response (OR), assessed by investigator using RECIST 1.1 criteria, relative to a regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
  • To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab, and trastuzumab will improve PFS, OR, and/or duration of objective response assessed by retrospective blinded central review using RECIST 1.1 criteria, relative to a regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
  • To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab, and trastuzumab will decrease the incidence of subsequent brain metastases in patients without known brain metastases at study entry relative to a regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
  • To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab, and trastuzumab will contribute to increased patient-reported fatigue in comparison to a regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
  • To determine the utility of PD-L1 immunohistochemistry (IHC) staining as a predictive and prognostic biomarker associated with clinical response, as assessed by investigator using RECIST 1.1 criteria, to atezolizumab in combination with paclitaxel, trastuzumab, and pertuzumab.
  • To determine the immune-related toxicity profile of the two treatment regimens.
  • To determine the cardiac safety profile of the two treatment regimens.
EXPLORATORY OBJECTIVES:
  • To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab, and trastuzumab will improve the progression-free survival and overall objective response, assessed by investigator using immune-modified RECIST (iRECIST) criteria, relative to a regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
  • To identify potential biomarkers that can predict benefit from the addition of atezolizumab in patients with newly documented HER2-positive measurable metastatic breast cancer treated with a regimen of paclitaxel, pertuzumab, and trastuzumab, and placebo.
  • To explore the toxicity profile of the two treatment regimens using patient-reported symptomatic adverse events in addition to standard adverse event reports.
  • To determine the feasibility and added value of frequent assessment of toxicity using Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) with electronic(e)PRO reporting.
OUTLINE:
Patients are randomized to 1 of 2 arms.

ARM I: Patients receive pertuzumab intravenously (IV) over 30-60 minutes on days 1 and 22, trastuzumab IV over 30-90 minutes on days 1 and 22, paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, and 36, and atezolizumab IV over 60 minutes on days 1 and 22. Cycles for pertuzumab, trastuzumab and atezolizumab repeat every 6 weeks and treatment with paclitaxel repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional 3 cycles of paclitaxel in the absence of progression at the investigator's discretion
ARM II: Patients receive pertuzumab, trastuzumab, and paclitaxel as in Arm I. Patients also receive placebo IV over 60 minutes on days 1 and 22. Cycles for pertuzumab, trastuzumab, and placebo repeat every 6 weeks and treatment with paclitaxel repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional 3 cycles of paclitaxel in the absence of progression at the investigator's discretion. After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for 4 years.

Voir cet essai sur ClinicalTrials.gov

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