- Written informed consent and any locally-required authorization (e.g., Health
Insurance Portability and Accountability Act [HIPAA] in the United States of America
[USA], European Union [EU] Data Privacy Directive in the EU) obtained from the subject
prior to performing any protocol-related procedures, including screening evaluations.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Hemoglobin >= 9.0 g/dL (transfusion is allowed to correct anemia).
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3).
- Platelet count >= 100 x 10^9/L (> 100,000 per mm^3).
- Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless diagnosed
with Gilbert's syndrome.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
unless liver metastases are present, in which case it must be =< 5 x ULN.
- Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula or by
24-hour urine collection for determination of creatinine clearance.
- Subjects must either be of non-reproductive potential (i.e., post-menopausal by
history: >= 60 years old and no menses for >= 1 year without an alternative medical
cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history
of bilateral oophorectomy) or must have a negative serum pregnancy test upon study
- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including
biopsies and follow up.
- Histology (reviewed at MD Anderson Cancer Center [MDACC]) showing recurrent high grade
epithelial ovarian, peritoneal, or fallopian tube cancer.
- Platinum resistant or refractory disease as defined by progression of disease on a
platinum-containing regimen or recurrence of disease within 180 days of previous
- Have measurable disease based on modified Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1. For the purposes of this study measurable disease is defined at least
one "target" lesion that can be accurately measured in at least one dimension (longest
dimension to be recorded). Each target lesion must be > 20 mm when measured by
conventional techniques, including palpation, plain x-ray, computed tomography (CT),
and magnetic resonance imaging (MRI), or > 10 mm when measured by spiral CT. The
target lesion must be distinct from other tumor areas selected for pre-treatment
biopsies. Pre-treatment imaging must be performed within 4 weeks of starting therapy.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).
- Previous enrollment or randomization in the present study.
- Participation in another clinical study with an investigational product administered
during the last 28 days.
- Any previous treatment with adoptive T cells therapy, a PD1 or PDL1 inhibitor,
including durvalumab or any anti-CTLA4 therapy, including tremelimumab.
- 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 study drug
and of low potential risk for recurrence; adequately treated non-melanoma skin cancer
or lentigo maligna without evidence of disease; or adequately treated carcinoma in
situ without evidence of disease, e.g., cervical cancer in situ.
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) =< 28 days prior to the first dose of study
drug (=< 21 days prior to the first dose of study drug for subjects who have received
prior tyrosine kinase inhibitors (TKIs) [e.g., erlotinib, gefitinib and crizotinib]
and =< 6 weeks for nitrosourea, mitomycin C, or bevacizumab). (If sufficient wash-out
time has not occurred due to the schedule or pharmacokinetics (PK) properties of an
agent, a longer wash-out period may be required.)
- Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3
electrocardiograms (ECGs) using Fridericia's correction.
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab OR tremelimumab, with the exceptions of intranasal and inhaled
corticosteroids or systemic corticosteroids at physiological doses, which are not to
exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroid premedication
for the prevention of radiologic contrast hypersensitivity is allowed.
- Any unresolved toxicity (> Common Terminology Criteria for Adverse Events [CTCAE]
grade 1) from previous anti-cancer therapy, excluding alopecia. Subjects with
irreversible toxicity greater than grade 1 that is not reasonably expected to be
exacerbated by the investigational product may be included (e.g., hearing loss,
- Any prior grade >= 3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE > grade 1.
- Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
- History of primary immunodeficiency.
- History of allogeneic organ transplant.
- History of hypersensitivity to durvalumab, tremelimumab, or any excipient.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent.
- Known history of previous clinical diagnosis of tuberculosis.
- History of leptomeningeal carcinomatosis or brain metastasis.
- Unresolved partial or complete small or large bowel obstruction.
- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab OR tremelimumab.
- Subjects who are pregnant, breast-feeding or of reproductive potential who are not
employing an effective method of birth control or 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.
- Any medical, social, or psychological condition that would interfere with evaluation
of study treatment or interpretation of patient safety or study results.
- Subjects with uncontrolled seizures.
- Non-English speakers will be excluded from participating in the patient-reported
outcomes component of the study.