Investigating Idetrexed and Olaparib in Patients With Ovarian Cancer

Inclusion criteria

• 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.

Exclusion criteria

• Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and 4 weeks for investigational medicinal products) before treatment.
• Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the DDU should not exclude the patient.
• Patients with new brain metastases. Patients with treated (surgically excised or irradiated) and stable brain metastases are eligible as long as the treatment was at least 4 weeks prior to initiation of study drug and brain MRI within 2 weeks of initiation of study drug is negative for new metastases.
• Patients with pulmonary metastases.
• History of thoracic radiation or other history likely to create pre-existing lung disease
• Presence of significant clinical ascites and/or pleural effusions.
• Female patients of child-bearing potential (or are already pregnant or lactating). However, those patients who have a negative serum or urine pregnancy test before enrolment and agree to use two forms of contraception (one effective form plus a barrier method) [oral, injected or implanted hormonal contraception and condom; intra-uterine device and condom; diaphragm with spermicidal gel and condom] or agree to sexual abstinence (see Protocol Section 16.5 - Appendix 5), effective from signing the consent form, throughout the trial and for six months afterwards are considered eligible.
• Major thoracic or abdominal surgery from which the patient has not yet recovered.
• Patients with sub-acute bowel obstruction.
• Organ transplant patients.
• At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
• Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
• Patients with history of QT prolongation, clinically significant VT, VF, heart block, MI within 1 year, CHF NYHA Class III or IV, unstable angina, angina within 6 months, or other evidence of clinically significant coronary artery disease/
• Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase I/Ib study of Idetrexed and Olaparib. Participation in an observational trial would be acceptable.
• Inability to tolerate Olaparib.
• Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
• Confirmed, current COVID-19 infection.