Clinical trial NCT05320757: Effects of PARP Inhibitor on Tumor Microenvironment in High-risk Endometrial Cancer Patients
Official title: Effects of PARP Inhibitor on Tumor Microenvironment in High-risk Endometrial Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Endometrial Cancer
Keywords: Endometrial cancer, olaparib
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2022-04-11
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Extent of DNA damage
timeFrame: Up to 18 months
Secondary outcomes:
measure: Change of CD4 and CD8 T cells in tumor
timeFrame: Up to 18 months
measure: Change of interferon gamma level in blood
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Ka Yu Tse
role: PRINCIPAL_INVESTIGATOR
References: