Study protocol for a multi-institutional randomized phase III study comparing combined everolimus plus lanreotide therapy and everolimus monotherapy in patients with unresectable or recurrent gastroenteropancreatic neuroendocrine tumors; Japan Clinical Oncology Group Study JCOG1901 (STARTER-NET study)

Pancreatology. 2020 Sep;20(6):1183-1188. doi: 10.1016/j.pan.2020.07.010. Epub 2020 Jul 25.


Everolimus is recognized as one of the standard drugs for the treatment of unresectable or recurrent gastroenteropancreatic neuroendocrine tumors (NET). However, recent evidence has suggested that addition of somatostatin analogs to everolimus may yield better survival outcomes as compared to everolimus alone. In April 2020, we have initiated a randomized phase III trial in Japan, to confirm the superiority of combined everolimus plus lanreotide therapy over everolimus monotherapy in patients with unresectable or recurrent gastroenteropancreatic NETs with poor prognostic factors (Ki-67 labeling index: LI 5%-20% or Ki-67 LI < 5% with diffuse liver metastases). We plan to enroll a total of 250 patients from 76 institutions over an accrual period of 5 years. The primary endpoint is progression-free survival. The key secondary endpoint is overall survival, with response rate, disease control rate, and proportion of patients with adverse events as the other secondary endpoints. This trial is registered with the Japan Registry of Clinical Trials as jRCT1031200023 [].

Keywords: Everolimus; Lanreotide; Neuroendocrine tumors; Randomized controlled trial.

Publication types

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

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Protocols*
  • Clinical Trials, Phase III as Topic
  • Endpoint Determination
  • Everolimus / administration & dosage
  • Female
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Intestinal Neoplasms / complications
  • Intestinal Neoplasms / drug therapy*
  • Japan
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / complications
  • Neuroendocrine Tumors / drug therapy*
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / drug therapy*
  • Peptides, Cyclic / administration & dosage
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic
  • Somatostatin / administration & dosage
  • Somatostatin / analogs & derivatives
  • Stomach Neoplasms / complications
  • Stomach Neoplasms / drug therapy*
  • Survival Analysis


  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Peptides, Cyclic
  • lanreotide
  • Somatostatin
  • Everolimus

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor