Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer

  • STATUS
    Recruiting
  • End date
    Jul 1, 2023
  • participants needed
    55
  • sponsor
    Leiden University Medical Center
Updated on 22 January 2021
platelet count
cancer
combination therapy
absolute neutrophil count
metastatic disease
measurable disease
endocrine therapy
gilbert's syndrome
metastasis
neutrophil count
hormone therapy
liver metastasis
liver metastases
durvalumab
uterine disease
parp inhibitor
olaparib
recurrent endometrial cancer
carcinosarcoma
uterine carcinosarcoma
carcinosarcoma of the uterus

Summary

The DOMEC trial is designed as a Dutch Gynecological Oncology Group (DGOG), prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer or carcinosarcoma of the uterus to investigate the efficacy of the combination therapy of olaparib tablets and durvalumab IV.

Description

The prognosis of recurrent or persistent endometrial carcinoma not amenable to local therapy is poor. First line therapy exists of platinum-based chemotherapy or hormonal therapy. No standard subsequent-line therapy has been described.The combination of Poly(ADP-ribose) polymerases (PARP) inhibition and Programmed death-ligand 1 (PD-L1) blocking has great potential in the treatment of recurrent endometrial cancer. The DOMEC trial is designed to investigate this treatment combination among all molecular subgroups.

The DOMEC trial is designed as a DGOG, prospective, multi-center, phase II study for 55 patients with advanced (recurrent, refractory or metastatic) endometrial cancer, including carcinosarcoma of the uterus. Patients must have had one prior platinum-based chemotherapeutic regimen or not be able/willing to get chemotherapy. The aim is to investigate the efficacy of the combination therapy of olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks in terms of progression free survival. Secondary objectives are to investigate objective response rate, overall survival, safety and predictive biomarkers.

Details
Condition Endometrial Carcinoma, Disorder of uterus NOS, Uterine Cancer, Endometrial Cancer, Uterine Disorders
Treatment PARP inhibitor and Anti-PD-L1
Clinical Study IdentifierNCT03951415
SponsorLeiden University Medical Center
Last Modified on22 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Are you female?
Do you have any of these conditions: Endometrial Carcinoma or Uterine Cancer?
Do you have any of these conditions: Endometrial Carcinoma or Uterine Disorders or Uterine Cancer or Endometrial Cancer or Disorder of uterus NOS?
Written informed consent
Age > 18 years old
Histologically confirmed diagnosis of endometrial cancer or carcinosarcoma of the endometrium
Metastatic disease or locally advanced tumor not amenable to local therapy
Documented progressive disease before enrolment
Measurable lesions outside irradiated field or progressive measurable lesions in irradiated area
Not eligible for hormonal therapy (because of negative hormone receptor/poor differentiation, or after failure of hormonal therapy)
Previous failure of chemotherapy, or refusal to undergo chemotherapy or chemo-naive patients not suitable for chemotherapy
WHO performance 0-1
Adequate organ system function as measured within 28 days prior to administration of study treatment, as defined below
Haemoglobin 10.0 g/dL, with no blood transfusion in the past 28 days
Absolute neutrophil count (ANC) 1.5 x 109/L
Platelet count 100 x 109/L
Total bilirubin 1.5 x institutional upper limit of normal (ULN) (not applicable to Gilbert's syndrome)
Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) 2.5 x ULN unless liver metastases are present in which case they must be 5x ULN
Patients must have creatinine clearance estimated of 51 mL/min estimated using the Cockcroft-Gault equation or 24 hr urine clearance
Life expectancy of at least 16 weeks
Measurable disease as defined by RECIST 1.1 criteria
Able to swallow and retain oral medication
A female is eligible to enter and participate in this study if there is

Exclusion Criteria

Participation in another clinical study with an investigational product during the last month or previous enrolment in the present study
Any previous treatment with PARP inhibitor, including olaparib and/or any previous treatment with a PD1 or PD-L1 inhibitor
History of another primary malignancy except for malignancy treated with curative intent and with no known active disease 5 years before the first dose of investigational product and of low potential risk for recurrence or adequately treated non-melanoma skin cancer, lentigo maligna or carcinoma in situ
History of leptomeningeal carcinomatosis, symptomatic uncontrolled brain metastases (2mg/ day corticosteroids started 4 weeks prior to treatment is accepted) and spinal cord compression (unless received definitive treatment and clinically stable for 28 days)
Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
Concomitant use of known strong or moderate CYP3A inhibitors and inducers
Any unresolved toxicity NCI CTCAE Grade 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab (except intranasal and inhaled corticosteroids or systemic prednisone 10 mg/day)
Major surgery 2 weeks of starting study treatment
History of active primary immunodeficiency
Active or prior documented autoimmune or inflammatory disorders, with exception of: vitiligo or alopecia, hypothyroidism stable on hormone replacement, any chronic skin condition that does not require systemic therapy, celiac disease controlled by diet alone
Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
Active infection including tuberculosis, hepatitis B/C and HIV
Patients with an expected or known hypersensitivity to olaparib or durvalumab or any of the excipients of the products
Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
Receipt of live attenuated vaccine within 30 days prior to the first dose of IP
Pregnancy or breastfeeding
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