A phase III, randomized, double blinded trial of platinum based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal, or peritoneal cancer and platinum treatment free interval of more than 6 months: ENGOT-Ov41/GEICO 69-O/ANITA Trial

Int J Gynecol Cancer. 2021 Apr;31(4):617-622. doi: 10.1136/ijgc-2020-001633. Epub 2020 Dec 14.

Abstract

Background: Platinum based chemotherapy is the treatment of choice for ovarian cancer patients with a platinum treatment free interval of >6 months. Niraparib is an oral poly (ADP-ribose) polymerase inhibitor approved as maintenance therapy after a response to platinum rechallenge, regardless of BRCA status. Atezolizumab is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). A combination of poly (ADP-ribose) polymerase inhibitor and anti-PD-L1/programmed cell death protein 1 (PD-1) has shown synergy in preclinical models and promising clinical activity.

Primary objective: To determine whether the addition of atezolizumab to carboplatin based chemotherapy and to subsequent maintenance with niraparib improves progression free survival compared with placebo in patients with recurrent disease and a platinum treatment free interval of >6 months.

Trial design: The Atezolizumab and NIraparib Treatment Association (ANITA) trial is a GEICO (Grupo Español de Investigación en Cáncer de Ovario) led phase III, randomized, double-blinded, multicenter European Network for Gynecological Oncological Trials (ENGOT) study. Patients will be randomized to arm A (control arm) consisting of platinum based chemotherapy (investigator's choice) plus a placebo of atezolizumab followed by maintenance niraparib plus a placebo of atezolizumab, or to arm B (experimental arm) consisting of platinum based chemotherapy (investigator's choice) plus atezolizumab followed by maintenance niraparib plus atezolizumab.

Major inclusion/exclusion criteria: Inclusion criteria are women aged over 18 years, diagnosed with relapsed high grade serous, endometrioid, or undifferentiated ovarian, fallopian tube, or primary peritoneal carcinoma. Patients are eligible if they received no more than two previous lines of chemotherapy, relapsed ≥6 months after the last platinum containing regimen, and have at least one measurable lesion according to the response evaluation criteria in solid tumors, version 1.1.

Primary endpoint: The primary endpoint for this study is progression free survival.

Sample size: Approximately 414 patients will be recruited and randomized in a 1:1 ratio, with the aim of demonstrating a benefit in progression free survival for the experimental arm with a hazard ratio of O.7, using a two sided alpha of 0.05 and a power of 80%.

Estimated dates for completing accrual and presenting results: The trial was launched in the fourth quarter of 2018 and is estimated to close in the second quarter of 2021. Mature results for progression free survival are expected to be presented by 2023.

Trial registration: Clinicaltrials.gov NCT03598270.

Keywords: medical oncology.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / mortality
  • Double-Blind Method
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / mortality
  • Female
  • Humans
  • Indazoles / pharmacology
  • Indazoles / therapeutic use*
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / mortality
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Platinum / pharmacology
  • Platinum / therapeutic use*
  • Progression-Free Survival
  • Time Factors

Substances

  • Antibodies, Monoclonal, Humanized
  • Indazoles
  • Piperidines
  • Platinum
  • atezolizumab
  • niraparib

Associated data

  • ClinicalTrials.gov/NCT03598270