Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer

• Status: Active, not recruiting
• Trial end date: 2021-08-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Leiden University Medical Center
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Amsterdam University Medical Center; AstraZeneca; Erasmus Medical Center; Maastricht University Medical Center; Radboud University; The Netherlands Cancer Institute; UMC Utrecht; University Medical Center Groningen
• Treatments: Antibodies; Antibodies, Monoclonal; Durvalumab; Olaparib; Poly(ADP-ribose) Polymerase Inhibitors

Criteria

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