A Cancer Research UK Randomised Phase II Trial of ATN-224 (Copper Binding Agent) in Combination With Exemestane Versus Exemestane Alone in Post-Menopausal Women With Recurrent or Advanced, Oestrogen and/or Progesterone Receptor Positive Breast Cancer
- Compare progression-free survival of postmenopausal women with, estrogen receptor-
and/or progesterone receptor-positive recurrent or advanced breast cancer treated with
exemestane with versus without SOD1 inhibitor ATN-224.
- Establish the safety of SOD1 inhibitor ATN-224 in combination with exemestane in these
- Determine the response rate (overall, at 16 and 24 weeks), response duration, and rate
of stable disease for ≥ 16 and ≥ 24 weeks in these patients.
- Determine the clinical benefit rate (complete response, partial response, and stable
disease) at 16 and 24 weeks in these patients.
- Investigate the time course of suppression of serum ceruloplasmin (Cp, surrogate for
- Investigate serum estradiol and estrone sulphate levels in these patients to assess if
SOD1 inhibitor ATN-224 interacts with the aromatase inhibition of exemestane.
- Investigate the pharmacokinetic behavior of SOD1 inhibitor ATN-224 in combination with
- Investigate superoxide dismutase 1 (SOD1) activity in red blood cells and cytokine
levels in plasma samples from these patients.
- Investigate circulating endothelial cell levels, circulating endothelial RNA levels,
and proteome profiles in blood samples at baseline and during treatment, from these
- Investigate SOD1, lysyl oxidase and copper-dependent proteins expression, and
endothelial growth factor receptor-related cell-signaling pathways in historical tumor
samples from all patients entered on the study.
OUTLINE: This is a multicenter study. Patients are stratified according to prior aromatase
inhibitor therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral exemestane and oral SOD1 inhibitor ATN-224 once daily.
- Arm II: Patients receive oral exemestane once daily. In both arms, treatment repeats
every 4 weeks in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for pharmacokinetic and pharmacodynamic
assessments, including Cp levels, estradiol and estrone sulfate, SOD1 levels, cytokines,
proteomics, circulating endothelial RNA, circulating endothelial cells, protein expression,
and EGFR-related cell signaling pathways.
After completion of study treatment patients are followed at 28 days.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Adrian L. Harris, MD
United States: Federal Government