Investigating Idetrexed and Olaparib in Patients With Ovarian Cancer

NCT ID: NCT06976892

Last Updated: 2025-08-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2029-12-31

Brief Summary

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.

Conditions

High Grade Serous Ovarian Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation

Patients may be assigned one of four dose levels for the combination of idetrexed and Olaparib:

• Dose Level 2 (starting dose): 9 mg/m2 idetrexed administered intravenously on days 1 and 15 of each cycle; 300 mg Olaparib administered orally twice per day on days 1-7 and 15-21.
• Dose Level 1: 9 mg/m2 idetrexed administered intravenously on days 1 and 15 of each cycle; 200 mg Olaparib administered orally twice per day on days 1-7 and 15-21.
• Dose Level -1: 9 mg/m2 idetrexed administered intravenously on days 1 and 15 of each cycle; 150 mg Olaparib administered orally twice per day on days 1-7 and 15-21.
• Dose Level 3: 12 mg/m2 idetrexed administered intravenously on days 1 and 15 of each cycle; 200 mg Olaparib administered orally twice per day on days 1-7 and 15-21.

Group Type: EXPERIMENTAL

Dose Level 2 (starting dose)

Intervention Type: DRUG

Idetrexed: 9 mg/m2 I.V. (days 1 \& 8) Olaparib: 300 mg P.O. (days1-7, 15-21)

Dose Level 1

Intervention Type: DRUG

Idetrexed: 9 mg/m2 I.V. (days 1 \& 8) Olaparib: 200 mg P.O. (days1-7, 15-21)

Dose Level -1

Intervention Type: DRUG

Idetrexed: 9 mg/m2 I.V. (days 1 \& 8) Olaparib: 150 mg P.O. (days1-7, 15-21)

Dose Level 3

Intervention Type: DRUG

Idetrexed: 12 mg/m2 I.V. (days 1 \& 8) Olaparib: 200 mg P.O. (days1-7, 15-21)

Dose Expansion

Only patients expressing high levels of alpha-folate receptor on their tumours will be eligible. The maximum tolerated dose of Olaparib in combination with idetrexed, based on safety and efficacy data from Dose Escalation, will inform the dose carried forward to Dose Expansion.

Group Type: EXPERIMENTAL

Maximum Tolerated Dose

Intervention Type: DRUG

MTD of Olaparib in combination with idetrexed established from Dose Escalation

Interventions

Dose Level 2 (starting dose)

Idetrexed: 9 mg/m2 I.V. (days 1 \& 8) Olaparib: 300 mg P.O. (days1-7, 15-21)

Intervention Type: DRUG

Dose Level 1

Idetrexed: 9 mg/m2 I.V. (days 1 \& 8) Olaparib: 200 mg P.O. (days1-7, 15-21)

Intervention Type: DRUG

Dose Level -1

Idetrexed: 9 mg/m2 I.V. (days 1 \& 8) Olaparib: 150 mg P.O. (days1-7, 15-21)

Intervention Type: DRUG

Dose Level 3

Idetrexed: 12 mg/m2 I.V. (days 1 \& 8) Olaparib: 200 mg P.O. (days1-7, 15-21)

Intervention Type: DRUG

Maximum Tolerated Dose

MTD of Olaparib in combination with idetrexed established from Dose Escalation

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Algok Bio Inc.

UNKNOWN

Sponsor Role: collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Professor Udai Banerji

Role: PRINCIPAL_INVESTIGATOR

Institute of Cancer Research, United Kingdom

Locations

Addenbrooke's Hospital

Cambridge, Cambridgeshire, United Kingdom

Site Status: NOT_YET_RECRUITING

Royal Marsden Hospital - Drug Development Unit

Sutton, London, United Kingdom

Site Status: RECRUITING

Velindre Cancer Centre

Cardiff, Wales, United Kingdom

Site Status: NOT_YET_RECRUITING

Countries

United Kingdom

Central Contacts

Alexander Cowley, Ph.D.

Role: CONTACT

idol@icr.ac.uk

+44 20 3437 6927

Anna Zachariou, Ph.D.

Role: CONTACT

idol@icr.ac.uk

Facility Contacts

Joo Ern Ang

Role: primary

jooern.ang1@nhs.net

Prof Udai Banerji, MBBS MD DNB PhD FRCP

Role: primary

udai.banerji@icr.ac.uk

Amy E Quinton

Role: primary

amy.quinton@wales.nhs.uk

Other Identifiers

1008393

Identifier Type: REGISTRY

Identifier Source: secondary_id

CCR5978

Identifier Type: -

Identifier Source: org_study_id