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

• Sponsor: The University of Hong Kong (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05320757
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 24
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer	Drug: Olaparib	Early Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effects of PARP Inhibitor on Tumor Microenvironment in High-risk Endometrial Cancer Patients
• Anticipated Study Start Date: Apr 1, 2022
• Anticipated Primary Completion Date: Dec 31, 2023
• Anticipated Study Completion Date: Mar 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Olaparib Olaparib: 300mg BID orally for 10 - 28 days (stop 3 - 4 days before definitive treatment)	Drug: Olaparib; a PARP inhibitor; Other Names: Lynparza

Outcome Measures

Primary Outcome Measures

1. 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

1. 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)

2. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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:

4. G3 endometrioid, any stage

5. Type 2 (such as serous, clear cell, carcinosarcoma), any stage

6. G1 endometrioid, stage 2 or beyond

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

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

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

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

11. Patients must be able to swallow oral medication

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

13. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Hong Kong	Hong Kong		Hong Kong

Sponsors and Collaborators

• The University of Hong Kong

Investigators

• Principal Investigator: Ka Yu Tse, The University of Hong Kong

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Ka-Yu Tse, Principal Investigator, The University of Hong Kong
• ClinicalTrials.gov Identifier: NCT05320757
• Other Study ID Numbers: UW 21-521
• First Posted: Apr 11, 2022
• Last Update Posted: Apr 11, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Dr. Ka-Yu Tse, Principal Investigator, The University of Hong Kong: Endometrial cancer, olaparib
• Additional relevant MeSH terms: Endometrial Neoplasms; Olaparib

Study Results

No Results Posted as of Apr 11, 2022