Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer

NCT03951415 | Unknown Phase 2 DMC

• 1 other identifier: DOMEC
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 8

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.

Conditions

Endometrial Neoplasms; Uterine Neoplasms; Endometrium Cancer

Keywords

Poly (ADP-ribose) Polymerase Inhibitors; Antibodies, Monoclonal; Checkpoint Inhibitors; olaparib; durvalumab; Anti-PD-L1

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  PFS will be counted from the date of registration until the first observation of radiological progressive disease according to RECIST 1.1 criteria or death due to any cause, whichever occurred first.

  6 months

Secondary Outcomes (4)

• Objective response rate (ORR)

  12 weeks

• Overall survival (OS)

  Through study completion, up to 36 months

• Adverse events

  Through study completion, up to 36 months

• Predictive biomarkers in tumor biopsy

  At baseline

Other Outcomes (3)

• Functional HRD assay (optional)

  At baseline

• Immunological effects of PARP-1 inhibition (optional)

  Change From Baseline to 6 weeks and 12 weeks

• Predictive biomarkers for PD-L1 blocking in blood (optional)

  Change From Baseline to 6 weeks and 12 weeks

Study Arms (1)

PARP inhibitor and Anti-PD-L1

EXPERIMENTAL

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

Drug: PARP inhibitor and Anti-PD-L1

Interventions

PARP inhibitor and Anti-PD-L1 DRUG

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

Also known as: olaparib, durvalumab, PARP inhibitor, Anti-PD-L1 Monoclonal Antibody

PARP inhibitor and Anti-PD-L1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Amsterdam University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• Maastricht University Medical Center: collaborator
• The Netherlands Cancer Institute: collaborator
• Radboud University Medical Center: collaborator
• University Medical Center Groningen: collaborator
• UMC Utrecht: collaborator
• AstraZeneca: collaborator

Study Sites (8)

Amsterdam UMC, AMC

Amsterdam, 1105 AZ, Netherlands

Location

NKI-AVL

Amsterdam, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, Netherlands

Location

Leiden University Medical Center

Leiden, 2300RC, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, Netherlands

Location

RadboudMC

Nijmegen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

MeSH Terms

Conditions

Endometrial Neoplasms; Uterine Neoplasms

Interventions

Poly(ADP-ribose) Polymerase Inhibitors; olaparib; durvalumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 30, 2019
• First Posted: May 15, 2019
• Study Start: July 8, 2019
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (8)