Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer

NCT ID: NCT03951415

Last Updated: 2021-04-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-08
• Study Completion Date: 2021-08-01

Brief 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.

Detailed 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.

Conditions

Endometrial Neoplasms; Uterine Neoplasms; Endometrium Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PARP inhibitor and Anti-PD-L1

olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks

Group Type: EXPERIMENTAL

PARP inhibitor and Anti-PD-L1

Intervention Type: DRUG

olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks

Interventions

PARP inhibitor and Anti-PD-L1

olaparib tablets 300mg twice daily orally and durvalumab 1500mg by IV infusion every 4 weeks

Intervention Type: DRUG

Other Intervention Names

olaparib; durvalumab; PARP inhibitor; Anti-PD-L1 Monoclonal Antibody

Eligibility 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:

• 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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amsterdam University Medical Center

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

J.R. Kroep

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Amsterdam UMC, AMC

Amsterdam, , Netherlands

NKI-AVL

Amsterdam, , Netherlands

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

RadboudMC

Nijmegen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Countries

Netherlands

Other Identifiers

DOMEC

Identifier Type: -

Identifier Source: org_study_id