Health TrialsbyHealthPanel

Investigating Idetrexed and Olaparib in Patients With Ovarian Cancer

ConditionHigh Grade Serous Ovarian Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexFemale
Age18+
SponsorInstitute of Cancer Research, United Kingdom

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Dose Level 2 (starting dose)

    Drug

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

  • Dose Level 1

    Drug

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

  • Dose Level -1

    Drug

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

  • Dose Level 3

    Drug

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

  • Maximum Tolerated Dose

    Drug

    MTD of Olaparib in combination with idetrexed established from Dose Escalation

Treatment groups

33 Participants
are divided into 2 treatment groups
Group A: Dose EscalationExperimental treatment 4 interventions
Group B: Dose ExpansionExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Propose a recommended dose/schedule for Phase II evaluation of the combination of Idetrexed and Olaparib

Endpoint: Maximum tolerated dose/ schedule (MTD) of the combination of Idetrexed and Olaparib based on dose-limiting toxicities (DLT) with target acceptable DLT rate of 25%, and the Recommended Phase II dose (RP2D) and schedule (Dose Escalation only).

Time frame
End of Cycle 2 (each cycle is 28 days)
2

Assess the safety and toxicity profile of Idetrexed and Olaparib

Endpoint: determining causality of each adverse event to Idetrexed and Olaparib and grading severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Dose Escalation and Dose Expansion).

Time frame
End of Cycle 6 (each cycle is 28 days)
3

Evaluate the preliminary anti-tumour activity of the combination of Idetrexed and Olaparib in alpha folate receptor overexpressing high grade serous ovarian cancer

Endpoint: Objective response rate by the occurrence of Best Overall Response (BOR) per RECIST 1.1 criteria (Dose Expansion only).

Time frame
Until patient withdraws due to radiological progression, or begins new line of therapy.

Secondary outcomes

1

Evaluate antitumour activity of the combination of Idetrexed and Olaparib

Endpoint: Progression Free Survival (PFS).

Time frame
From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
2

Evaluate the preliminary anti-tumour activity of the combination of Idetrexed and Olaparib in ovarian cancer irrespective of alpha folate receptor expression status

Objective response rate.

Time frame
From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
3

CA125 responses

Measurement of CA125 levels.

Time frame
From date of enrolment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

Other outcomes

1

(Tertiary Objective): Retrospective evaluation of response biomarkers

Alpha-folate expression.

Time frame
Within four weeks of patient beginning treatment.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institute of Cancer Research, United Kingdom

Lead sponsor

Algok Bio Inc.

Collaborator

Source ClinicalTrials.gov
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