None listed
Conditions
Brief summary
The primary purpose of this trial is to evaluate the safety and efficacy of durvalumab for the treatment of advanced endometrial cancer. Who is it for? You may be eligible to enroll in this trial if you are aged 18 or over and have been diagnosed with advanced endometrial carcinoma which is suitable for chemotherapy. Study details All participants enrolled in this trial will receive an intravenous dose of durvalumab once every 28 days until the cancer is seen to have progressed, or until treatment side effects become intolerable. Participants will undergo continuous monitoring for side effects throughout treatment, as well as completing questionnaires and blood tests every four weeks, and CT scans every 8 to 12 weeks for the duration of treatment. It is hoped that this trial will provide information on whether durvalumab is safe and effective for the treatment of advanced endometrial cancer.
Interventions
Participants meeting the inclusion criteria of either MMR-proficient or MMR-deficient will be registered and administered 1500 mg durvalumab intravenously every 28 days until disease progression or prohibitive toxicity.
Sponsors
University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with advanced endometrial carcinoma suitable for chemotherapy Adults, aged 18 years and older, with histologically or cytologically confirmed adenocarcinoma of endometrial origin Advanced or recurrent disease that is not amenable to local therapy with curative intent such as surgical resection and/or radiotherapy Assessment result for DNA mismatch repair (MMR) protein expression in tumour tissue by immunohistochemistry (IHC) must be available. This must include assessment for 4 MMR proteins: MLH1, MSH2, MSH6 and PMS2 Tumour tissue (FFPE) available for PD-L1 testing at a central laboratory Agreement to undergo a repeat core biopsy of tumour tissue if the only available tumour tissue sample was obtained before previous chemotherapy or more than 1 year previously, and the investigator judges that the lesion can be biopsied without undue risk. At least 1 target lesion according to RECIST v1.1 ECOG performance status of 0-2 Adequate bone marrow, renal and liver function Willing and able to start treatment within 7 days of registration and to comply with all study requirements, including the timing and/or nature of the required treatment and assessments
Exclusion criteria
Suspected brain or leptomeningeal metastases, untreated brain metastases or current clinical or radiological progression of known brain metastases, or requirement for steroid therapy for brain metastases. Patients with treated brain metastases are eligible if they have been stable and off steroids for 3 weeks or longer. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks before registration, or persisting adverse events (>Grade 1) due to a previously administered agent. Any condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone or equivalent dose of alternative corticosteroid) or other immunosuppressive medications within 28 days of durvalumab administration. Intranasal, inhaled or topical steroids are permitted in the absence of active autoimmune disease. History of any known or suspected autoimmune disease other than vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring only hormone replacement, or psoriasis not requiring systemic treatment within the last 2 years. Prior allogeneic organ transplant, inflammatory bowel disease, pneumonitis, tuberculosis, or primary immunodeficiency. Prior treatment with durvalumab, or with any other anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways. Life expectancy of less than 12 weeks. Systemic infection requiring IV antibiotics within 14 days before the first dose of durvalumab. Receipt of live attenuated vaccination within 30 days prior to enrolment. Known history of interstitial lung disease from any cause Mean QT interval corrected for heart rate (QTc) greater than or equal to 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction Myocardial infarction with 6 months prior to enrolment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, or active conduction system abnormalities. History of another malignancy within 3 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years after definitive primary treatment. Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol. Pregnancy, lactation, or inadequate contraception. Participants must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration.
Outcome results
None listed