Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer (DOMEC)

This is an interventional treatment trial for Endometrial Neoplasms focused on measuring Poly (ADP-ribose) Polymerase Inhibitors, Antibodies, Monoclonal, Checkpoint Inhibitors, olaparib, durvalumab, Anti-PD-L1 Read More

Inclusion criteria:

• 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