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This is a window study where treatment-naïve patients will receive olaparib before definitive treatment. The aim is to evaluate the DNA damage and inflammatory response after PARP inhibitor.
Patients with high-risk endometrial cancers are prone to develop recurrence. The response rate to conventional chemotherapy in persistent or recurrent endometrial cancer is poor. Recent research demonstrated that immune checkpoint with or without targeted therapy was an effective treatment option. However, the change of immune landscape in the blood and tumor after PARPi is not clear.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Olaparib | Experimental | Olaparib: 300mg BID orally for 10 - 28 days (stop 3 - 4 days before definitive treatment) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Olaparib | Drug | a PARP inhibitor |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Extent of DNA damage | change of gH2Ax expression in tumor tissues in high-risk EC patients before and after olaparib as assessed by immunofluorescent staining (% change) | Up to 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change of CD4 and CD8 T cells in tumor | Change of T cell population in tumours before and after olaparib as assessed by immunostaining (% change) | Up to 18 months |
| Change of interferon gamma level in blood |
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Inclusion Criteria:
Patients must be capable of giving signed informed consent
Patients must be at least 18 years old
Patients must have newly diagnosed and histologically confirmed high-risk endometrial cancer, including:
The endometrial cancer should be visible on pre-treatment ultrasound, or endometrial lining should be 5mm or above
An archived FFFE sample of endometrial biopsy or at least 8 unstained slides should be available
Patients should have Eastern Cooperative Oncology Group (ECOG) performance score 0 to 1
Patients must have adequate bone marrow, renal, hepatic, thyroid and neurological function within 28 days prior to administration of study treatment
Patients must be able to swallow oral medication
Patients must have a life expectancy of ≥ 16 weeks
Patients must either be postmenopausal or show evidence of non-childbearing status for women of childbearing potential
Exclusion Criteria:
9. Concomitant use of known strong CYP3A inhibitors or inducer are excluded. 10. Patients who have major surgery within 2 weeks, previous allogenic bone marrow transplant, are excluded.
11. Patients with a known hypersensitivity to olaparib or any of the excipients of the product are excluded.
12. Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, proceeding the first dose of study drug is not allowed.
13. Pregnant or breastfeeding women are excluded. 14. Patients who are judged by the investigator to be unlikely to comply with study procedures, restrictions and requirements are excluded.
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| Name | Affiliation | Role |
|---|---|---|
| Ka Yu Tse | The University of Hong Kong | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Hong Kong | Hong Kong | Hong Kong |
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| ID | Term |
|---|---|
| D016889 | Endometrial Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C531550 | olaparib |
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Change of interferon gamma in blood before and after olaparib as assessed by ELISA (% change)
| Up to 18 months |
| D009369 |
| Neoplasms |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |