A Phase I/Ib Trial of Idetrexed (Alpha Folate Receptor Targeted Thymidylate Synthase Inhibitor) in Combination With Olaparib (a PARP Inhibitor) at Different Doses in Patients With Ovarian Cancer (IDOL)
Two drugs called Idetrexed and olaparib are being evaluated. Idetrexed is a type of drug called an aFR-targeted thymidylate synthase inhibitor. Idetrexed has been designed to selectively target cancer cells that have a protein called folate receptor on the surface of cancer cells. Thymidylate synthase is key to cancer cells for creating new DNA when they multiply. Blocking the action of thymidylate synthase with a drug like Idetrexed may therefore stop cancers from growing by damaging DNA in cancer cells. Olaparib is a type of drug called a PARP inhibitor. It prevents cells repairing DNA damage. This leads to cells dying. Combining Idetrexed and olaparib should increase the number of cancer cells dying, especially those cells that have a lot of folate receptors. Cancer cells with a high number of folate receptors should be targeted more than normal healthy cells.
• Histologically or cytologically proven high grade serous ovarian cancer refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient.
• Measurable (as defined by RECIST v1.1) or evaluable (based on tumour markers) disease.
• Life expectancy of at least 12 weeks.
• World Health Organisation (WHO) performance status of 0-1 (Appendix 1 of Protocol).
• Haematological and biochemical indices within the ranges shown in Protocol section 4.1.1). These measurements must be performed within one week (Day -7 to Day 1) prior to the patient's first dose of IMP.
⁃ Normal (no clinically significant abnormalities) 12-lead ECG, QTcF interval \<470 ms
• Pulmonary function test FVC of \>70%, DLCOc (DLCO corrected for Hb) of \>60%.
• 18 years or over.
• Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.
• For dose expansion patients only, they must have medium to high α-folate receptor expression according to the Ventana FOLR1-2.1 IHC assay.