A Phase II Trial of Vandetanib in Children and Adults with Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumor

Clin Cancer Res. 2019 Nov 1;25(21):6302-6308. doi: 10.1158/1078-0432.CCR-19-0986. Epub 2019 Aug 22.


Purpose: Gastrointestinal stromal tumors (GIST) are resistant to cytotoxic chemotherapy and radiotherapy. Most GIST in children are wild-type for KIT and PDGFRA (WT GIST) and deficient in expression of succinate dehydrogenase (dSDH GIST). We tested the activity of vandetanib, an oral small-molecule inhibitor of VEGFR2, EGFR, and RET, in patients with dSDH GIST.

Patients and methods: Phase II study of vandetanib (300 mg orally once daily to patients ≥18 years, and 100 mg/m2/dose to patients < 18 years) on a continuous dosing schedule (1 cycle = 28 days) to assess the clinical activity (partial and complete response rate RECIST v1.1) in patients with dSDH GIST. A Simon optimal two-stage design (target response rate 25%, rule out 5%) was used: If ≥1 of 9 patients in stage 1 responded, enrollment would be expanded to 24 patients, and if ≥3 of 24 responded, vandetanib would be considered active.

Results: Nine patients (7 female and 2 male; median age, 24 years; range, 11-52) with metastatic disease were enrolled. Three of the initial 5 adult patients developed treatment-modifying toxicities. After a protocol amendment, two adults received vandetanib at 200 mg/dose with improved tolerability. The two children (<18 years old) enrolled did not experience treatment-modifying toxicities. No partial or complete responses were observed (median number of cycles, 4; range, 2-18).

Conclusions: Vandetanib at a dose of 300 mg daily was not well tolerated by adults with dSDH GIST. Two of 9 patients had prolonged stable disease, but no partial or complete responses were observed, and vandetanib is thus not considered active in dSDH GIST.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Disease-Free Survival
  • Female
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Metastasis
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Progression-Free Survival
  • Proto-Oncogene Proteins c-kit / genetics
  • Quality of Life
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Succinate Dehydrogenase / genetics*
  • Young Adult


  • Piperidines
  • Quinazolines
  • Succinate Dehydrogenase
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha
  • N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine