| Eligibility |
Inclusion Criteria:
I-1 Female patients must be = 18 years of age. I-2 Signed informed consent and ability to
comply with treatment and follow-up. I-3 Patients with newly histologically confirmed
epithelial ovarian cancer (or fallopian tube or primary peritoneal adenocarcinoma).
I-4 Advanced FIGO stage IIIC to IV. I-5 Patients for whom primary debulking surgery has
been denied after an evaluation through laparoscopy or laparotomy.
I-6 Patient for whom a neo-adjuvant strategy has been planned. I-7 Interval between
diagnosis and enrolment (informed consent signed) = 8 weeks.
I-8 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. I-9 Geriatric
vulnerability score (GVS) < 3 for patients = 70 years. I-10 Adequate organ and bone marrow
function. I-11 Patients not receiving anticoagulant medication who have an International
Normalized Ratio (INR) = 1.5 and an Activated ProThrombin Time (aPTT) = 1.5 x ULN. The use
of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is
within therapeutic limits (according to site medical standard) and if the patient is on a
stable dose of anticoagulants for at least two weeks at the time of randomization.
I-12 As this study will include patients in France, a subject will be eligible for
randomization in this study only if either affiliated to, or a beneficiary of, a social
category.
Exclusion Criteria:
E-1 Other malignancy within the last 5 years except: adequately treated non-melanoma skin
cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS).
E-2 Major surgical procedure (defined by the resection of at least one organ including
ovary) within 28 days prior to the first dose.
E-3 Any concurrent chemotherapy, investigational product, biological, or hormonal therapy
for cancer treatment.
E-4 Previous treatment with immunotherapy, including, but not limited to, anti-CTLA-4,
anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, or therapeutic anticancer vaccine.
E-5 Active or prior documented autoimmune or inflammatory disorders The following are
exceptions to this criterion:
1. Patients with vitiligo or alopecia,
2. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone
replacement or psoriasis not requiring systemic treatment.
E-6 Current/prior immunosuppressive medication = 14 days before first durvalumab and
tremelimumab dose (including, but not limited to, prednisone, dexamethasone,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor
[TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for
systemic immunosuppressive medications during the trial.
E-7 Immunocompromised patients, e.g., patients who are known to be serologically positive
for human immunodeficiency virus (HIV). Patients with active hepatitis B (defined as having
a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients
with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a
negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody
test) are eligible.
E-8 Uncontrolled diabetes mellitus, uncontrolled hypothyroidism. E-9 Treatment with
systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-a)
and interleukin-2 (IL-2) within 4 weeks or five half- lives of the drug (whichever is
shorter) prior to Cycle 1, Day 1.
E-10 History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
pneumonia), or evidence of active pneumonitis. Radiation pneumonitis in the radiation field
(fibrosis) detected on screening chest CT scan is permitted.
E-11 Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. E-12
Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or
anticipation that such a live attenuated vaccine will be required during the study.
Influenza vaccination should be given during influenza season only (example approximately
October to March in the Northern Hemisphere). Patients must not receive live, attenuated
influenza.
E-13 Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325
mg/day.
E-14 Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
E-15 Inadequately controlled HTN (defined as systolic blood pressure > 150 mmHg and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications).
E-16 Clinically significant (e.g. active) cardiovascular disease, including:
1. Myocardial infarction or unstable angina within = 6 months of randomization,
2. New York Heart Association (NYHA) = grade 2 congestive heart failure (CHF),
3. Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled
atrial fibrillation are eligible),
4. Peripheral vascular disease grade = 3 (e.g. symptomatic and interfering with
activities of daily living [ADL] requiring repair or revision).
E-17 Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or
Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.
E-18 History or evidence of hemorrhagic disorders within 6 months prior to randomization.
E-19 Evidence of bleeding diathesis or significant coagulopathy (in the absence of
coagulation).
E-20 History or clinical suspicion of brain metastases or spinal cord compression unless
asymptomatic, treated, and stable off steroids and anti-convulsants for at least 1 month
prior to entry.
E-21 History or evidence upon neurological examination of central nervous system (CNS)
disease, unless adequately treated with standard medical therapy (e.g. uncontrolled
seizures).
E-22 Pre-existing motor or sensory neurotoxicity (grade > 1). E-23 Significant traumatic
injury within 4 weeks prior to randomization. E-24 Non-healing wound, active ulcer or bone
fracture. Patients with granulating incisions healing by secondary intention with no
evidence of facial dehiscence or infection are eligible but require 3 weekly wound
examinations.
E-25 Current, clinically relevant bowel obstruction, including sub-occlusive disease,
related to underlying disease.
E-26 Previous allogeneic bone marrow transplant or previous solid organ transplantation.
E-27 Patients with evidence of abdominal free air not explained by paracentesis or recent
surgical procedure.
E-28 Evidence of any other disease, metabolic dysfunction, physical examination finding or
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or puts the patient at high risk for
treatment related complications.
E-29 Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential (< 2 years after last menstruation and not surgically sterile) who
are not willing to employ effective birth control from screening to 180 days after the last
dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of
durvalumab monotherapy, whichever is the longer time period.
E-30 History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins.
E-31 Known hypersensitivity or allergy to biopharmaceuticals or to any component of the
durvalumab or tremelimumab formulations.
E-32 Known hypersensitivity reaction or allergy to drugs chemically related to carboplatin,
paclitaxel, or their excipients that contraindicates the subject's participation.
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