Effects of PARP Inhibitor on Tumor Microenvironment in High-risk Endometrial Cancer Patients

Early Phase 1

Recruiting

• Conditions: Endometrial Cancer
• Interventions: Drug: Olaparib

• Registration Number: NCT05320757
• Lead Sponsor: The University of Hong Kong

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2022-02-23
• Study Start: 2022-04-01
• Study First Submitted QC: 2022-04-02
• Study First Posted: 2022-04-11
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-30
• Last Update Posted: 2023-10-03
• Primary Completion: 2024-12-31
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

1. Patients must be capable of giving signed informed consent

2. Patients must be at least 18 years old

3. Patients must have newly diagnosed and histologically confirmed high-risk endometrial cancer, including:

   1. G3 endometrioid, any stage
   2. Type 2 (such as serous, clear cell, carcinosarcoma), any stage
   3. G1 endometrioid, stage 2 or beyond

4. The endometrial cancer should be visible on pre-treatment ultrasound, or endometrial lining should be 5mm or above

5. An archived FFFE sample of endometrial biopsy or at least 8 unstained slides should be available

6. Patients should have Eastern Cooperative Oncology Group (ECOG) performance score 0 to 1

7. Patients must have adequate bone marrow, renal, hepatic, thyroid and neurological function within 28 days prior to administration of study treatment

8. Patients must be able to swallow oral medication

9. Patients must have a life expectancy of ≥ 16 weeks

10. Patients must either be postmenopausal or show evidence of non-childbearing status for women of childbearing potential

Exclusion Criteria

1. Patients with other malignancy unless curatively treated with no evidence of disease for >= 5 years, are excluded.

2. Patients whose resting ECG indicating uncontrolled, potentially reversible cardiac conditions, or patients with congenital long QT syndrome, are excluded.

3. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML, other hematological diseases such as venous or arterial thrombosis and thrombocytopenia are excluded.

4. Patients with symptomatic uncontrolled brain metastases are excluded.

5. Patients who are unable to swallow orally administered medication and gastrointestinal disorders are excluded.

6. Patients with immunocompromised condition, active hepatitis, or persistent toxicities caused by previous cancer therapy, are excluded.

7. 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.

8. Patients with a known hypersensitivity to olaparib or any of the excipients of the product are excluded.

9. 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.

10. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Olaparib	Olaparib	Olaparib: 300mg BID orally for 10 - 28 days (stop 3 - 4 days before definitive treatment)

Primary Outcome Measures

Name	Time	Method
Extent of DNA damage	Up to 18 months	change of gH2Ax expression in tumor tissues in high-risk EC patients before and after olaparib as assessed by immunofluorescent staining (% change)

Secondary Outcome Measures

Name	Time	Method
Change of CD4 and CD8 T cells in tumor	Up to 18 months	Change of T cell population in tumours before and after olaparib as assessed by immunostaining (% change)
Change of interferon gamma level in blood	Up to 18 months	Change of interferon gamma in blood before and after olaparib as assessed by ELISA (% change)

Trial Locations

Locations (1)

The University of Hong Kong; 🇭🇰 Hong Kong, Hong Kong