Phase I trial of systemic intravenous infusion of interleukin-13-Pseudomonas exotoxin in patients with metastatic adrenocortical carcinoma

Cancer Med. 2015 Jul;4(7):1060-8. doi: 10.1002/cam4.449. Epub 2015 Mar 13.


Adrenocortical carcinoma (ACC) is a rare but lethal malignancy without effective current therapy for metastatic disease. IL-13-PE is a recombinant cytotoxin consisting of human interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin A (PE). The main objectives of this Phase I dose-escalation trial were to assess the maximum-tolerated dose (MTD), safety, and pharmacokinetics (PK) of IL-13-PE in patients with metastatic ACC. Eligible patients had confirmed IL-13 receptor alpha 2 (IL-13Rα2) expressions in their tumors. IL-13-PE at dose of 1-2 μg/kg was administered intravenously (IV) on day 1, 3, and 5 in a 4-week cycle. Six patients received 1 μg/kg and two patients received 2 μg/kg of IL-13-PE. Dose-limiting toxicity was observed at 2 μg/kg, at which patients exhibited thrombocytopenia and renal insufficiency without requiring dialysis. PK analysis demonstrated that at MTD, the mean maximum serum concentration (Cmax ) of IL-13-PE was 21.0 ng/mL, and the terminal half-life of IL-13-PE was 30-39 min. Two (25%) of the eight patients had baseline neutralizing antibodies against PE. Three (75%) of the remaining four tested patients developed neutralizing antibodies against IL-13-PE within 14-28 days of initial treatment. Of the five patients treated at MTD and assessed for response, one patient had stable disease for 5.5 months before disease progression; the others progressed within 1-2 months. In conclusion, systemic IV administration of IL-13-PE is safe at 1 μg/kg. All tested patients developed high levels of neutralizing antibodies during IL-13-PE treatment. Use of strategies for immunodepletion before IL-13-PE treatment should be considered in future trials.

Keywords: IL-13-PE; Phase I; maximum-tolerated dose; metastatic adrenocortical carcinoma; pharmacokinetics; systemic administration.

Publication types

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

MeSH terms

  • ADP Ribose Transferases*
  • Adolescent
  • Adrenal Cortex Neoplasms / drug therapy*
  • Adrenal Cortex Neoplasms / pathology*
  • Adrenal Cortex Neoplasms / therapy
  • Adrenocortical Carcinoma / drug therapy*
  • Adrenocortical Carcinoma / pathology*
  • Adrenocortical Carcinoma / therapy
  • Adult
  • Aged
  • Antibodies, Neutralizing / blood
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Bacterial Toxins*
  • Exotoxins*
  • Female
  • Humans
  • Infusions, Intravenous
  • Interleukin-13*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Metastasis
  • Pseudomonas aeruginosa Exotoxin A
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / pharmacokinetics
  • Retreatment
  • Treatment Outcome
  • Virulence Factors*
  • Young Adult


  • Antibodies, Neutralizing
  • Antineoplastic Agents
  • Bacterial Toxins
  • Exotoxins
  • Interleukin-13
  • Recombinant Fusion Proteins
  • Virulence Factors
  • ADP Ribose Transferases