Randomised phase II trial to investigate catumaxomab (anti-EpCAM × anti-CD3) for treatment of peritoneal carcinomatosis in patients with gastric cancer

Br J Cancer. 2018 Aug;119(3):296-302. doi: 10.1038/s41416-018-0150-6. Epub 2018 Jul 10.

Abstract

Background: Peritoneal carcinomatosis (PC) represents an unfavourable prognostic factor for patients with gastric cancer (GC). Intraperitoneal treatment with the bispecific and trifunctional antibody catumaxomab (EpCAM, CD3), in addition to systemic chemotherapy, could improve elimination of PC.

Methods: This prospective, randomised, phase II study investigated the efficacy of catumaxomab followed by chemotherapy (arm A, 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, FLOT) or FLOT alone (arm B) in patients with GC and PC. Primary endpoint was the rate of macroscopic complete remission (mCR) of PC at the time of second diagnostic laparoscopy/laparotomy prior to optional surgery.

Results: Median follow-up was 52 months. Out of 35 patients screened, 15 were allocated to arm A and 16 to arm B. mCR rate was 27% in arm A and 19% in arm B (p = 0.69). Severe side effects associated with catumaxomab were nausea, infection, abdominal pain, and elevated liver enzymes. Median progression-free (6.7 vs. 5.4 months, p = 0.71) and overall survival (13.2 vs. 13.0 months, p = 0.97) were not significantly different in both treatment arms.

Conclusions: Addition of catumaxomab to systemic chemotherapy was feasible and tolerable in advanced GC. Although the primary endpoint could not be demonstrated, results are promising for future investigations integrating intraperitoneal immunotherapy into a multimodal treatment strategy.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Bispecific / administration & dosage*
  • Antibodies, Bispecific / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • CD3 Complex / antagonists & inhibitors
  • CD3 Complex / genetics
  • Docetaxel / administration & dosage
  • Epithelial Cell Adhesion Molecule / antagonists & inhibitors
  • Epithelial Cell Adhesion Molecule / genetics
  • Female
  • Fluorouracil / administration & dosage
  • Gastrectomy
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxaliplatin / administration & dosage
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / surgery
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology

Substances

  • Antibodies, Bispecific
  • CD3 Complex
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Oxaliplatin
  • Docetaxel
  • catumaxomab
  • Leucovorin
  • Fluorouracil