Phase II study of niraparib in recurrent or persistent rare fraction of gynecologic malignancies with homologous recombination deficiency (JGOG2052)

J Gynecol Oncol. 2022 Jul;33(4):e55. doi: 10.3802/jgo.2022.33.e55. Epub 2022 May 3.


Background: Poly (adenosine diphosphate)-ribose polymerase (PARP) inhibitors for tumors with homologous recombination deficiency (HRD), including pathogenic mutations in BRCA1/2, have been developed. Genomic analysis revealed that about 20% of uterine leiomyosarcoma (uLMS) have HRD, including 7.5%-10% of BRCA1/2 alterations and 4%-6% of carcinomas of the uterine corpus, and 2.5%-4% of the uterine cervix have alterations of BRCA1/2. Preclinical and clinical case reports suggest that PARP inhibitors may be effective against those targets. The Japanese Gynecologic Oncology Group (JGOG) is now planning to conduct a new investigator-initiated clinical trial, JGOG2052.

Methods: JGOG2052 is a single-arm, open-label, multi-center, phase 2 clinical trial to evaluate the efficacy and safety of niraparib monotherapy for a recurrent or persistent rare fraction of gynecologic malignancies with BRCA1/2 mutations except for ovarian cancers. We will independently consider the effect of niraparib for uLMS or other gynecologic malignancies with BRCA1/2 mutations (cohort A, C) and HRD positive uLMS without BRCA1/2 mutations (cohort B). Participants must have 1-3 lines of previous chemotherapy and at least one measurable lesion according to RECIST (v.1.1). Niraparib will be orally administered once a day until lesion exacerbation or unacceptable adverse events occur. Efficacy will be evaluated by imaging through an additional computed tomography scan every 8 weeks. Safety will be measured weekly in cycle 1 and every 4 weeks after cycle 2 by blood tests and physical examinations. The sample size is 16-20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate.

Trial registration: Japan Primary Registries Network (JPRN) Identifier: jRCT2031210264.

Keywords: Gene; Gynecologic Neoplasms; Homologous Recombination Repair; Leiomyosarcoma; Mutation; Poly(ADP-ribose) Polymerase Inhibitors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Trials, Phase II as Topic
  • Female
  • Genital Neoplasms, Female* / drug therapy
  • Genital Neoplasms, Female* / genetics
  • Homologous Recombination
  • Humans
  • Indazoles / adverse effects
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Piperidines


  • Indazoles
  • Piperidines
  • niraparib