Advanced (recurrent, refractory or metastatic) Endometrial cancer or carcinosarcoma of the uterus
Conditions
Interventions
olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks
Sponsors
Leiden University Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: To be included into the DOMEC-trial, patients must be (1) at least 18 years old, (2) have a WHO performance score of 0-1, (3) weight more than 30kg and (4) have histologically confirmed diagnosis of EC or carcinosarcoma of the uterus. There must be (5) a documented progressive disease (metastatic or locally advanced) according to RECIST 1.1 criteria. (6) Disease must be not amendable to local therapy, chemotherapy and hormonal therapy (or patient is not able/willing to get chemotherapy). (7) Organ system function should be adequate, defined as adequate bone marrow function (Haemoglobin = 10.0 g/dL, Absolute neutrophil count (ANC) = 1.5 x 10^9 /L, Platelet count = 100 x 10^9 /L), liver function (Total bilirubin = 1.5 x institutional upper limit of normal (ULN), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 2.5 x ULN (in case of lever metastases = 5x ULN) and kidney function (creatinine clearance =51 mL/min calculated according to Cockcroft-Gault or 24 hour urine clearance). (8) Life expectancy must be at least 16 weeks.
Exclusion criteria
Exclusion criteria: Patients with (1) history of leptomeningeal carcinomatosis, symptomatic brain metastases (uncontrolled despite of corticosteroids) or spinal cord compression are not eligible. Other exclusion criteria are (2) severe concomitant diseases; (3) active or prior documented autoimmune or inflammatory disorders; (4) active primary immunodeficiency; (5) active infections including tuberculosis, HIV, hepatitis B or C or (6) other malignant disease (except adequately treated non-melanoma skin cancer, lentigo maligna or carcinoma in situ without evidence of disease). (7) Prior treatment with PARP, PD1 or PD-L1 inhibitor; (8) QTc interval or family history of long QT syndrome; (9) severe psychiatric illness; (10) irreversible grade =2 toxicity from previous anti-cancer therapy; (11) major surgery in the last 2 weeks; (12) prior allogeneic bone marrow transplantation or double umbilical cord blood transplantation; (13) inability to swallow oral medication; (14) concurrent treatment with another investigational agent during the conduct of the trial or (15) expected or known intolerance to olaparib or durvalumab will prohibit inclusion; as well as (16) pregnancy or breast feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival | — |
Secondary
| Measure | Time frame |
|---|---|
| • Objective response rate (ORR) according to RECIST 1.1 criteria • Overall survival (OS) • Adverse events assessed by NCI Common Terminology Criteria for adverse Events (CTCAE) version 5.0 • Predictive biomarkers Optional endpoints: • Baseline functional homologous recombination deficiency-assay • Immunological effects of PARP-1 inhibition measured by tests for T cell and APC functionality and predictive biomarkers for PD-L1 blocking in blood | — |
Contacts
Public ContactJudith Kroep
LUMC
Outcome results
None listed