Durvalumab and Tremelimumab in Treating Participants With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Randomized Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab Administered in Combination Versus Sequentially in Recurrent Platinum-Resistant Epithelial Ovarian Cancer
2 other identifiers
interventional
100
1 country
1
Brief Summary
This phase II trial studies how well durvalumab and tremelimumab work in treating participants with ovarian, primary peritoneal, or fallopian tube cancer that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether give durvalumab and tremelimumab in combination or sequential administration works better in treating participants with ovarian, primary peritoneal, or fallopian tube cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2017
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 10, 2017
CompletedFirst Posted
Study publicly available on registry
January 20, 2017
CompletedStudy Start
First participant enrolled
May 18, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 11, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 11, 2025
CompletedSeptember 19, 2025
September 1, 2025
8.3 years
January 10, 2017
September 15, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Immune-related progression-free survival (irPFS)
Up to 4 years
Study Arms (2)
Arm I (sequential tremelimumab, durvalumab)
EXPERIMENTALPatients receive tremelimumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Upon progression, patients then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity. This arm is closed to enrollment.
Arm II (combination tremelimumab, durvalumab)
EXPERIMENTALPatients receive tremelimumab IV and durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
- Age \>/= 18 years at time of study entry.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate normal organ and marrow function as defined by: 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; AST and ALT \</= 2.5 x ULN unless liver metastases are present, in which case it must be \</= 5x ULN; Serum creatinine CL \>40 mL/min by the Cockcroft-Gault formula ( Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Creatinine CL (mL/min) = \[Weight (kg) x (140 - Age) x 0.85\]/\[72 x serum creatinine (mg/dL)\].
- 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 entry.
- 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 MDACC) showing recurrent high grade epithelial ovarian, peritoneal, or fallopian tube cancer of clear cell histology or mixed carcinoma with a clear cell component. In addition, subjects for the molecularly defined expansion cohort will also include patients with recurrent uterine serous carcinoma (who have received at least one prior line of platinum-based chemotherapy), and must have somatic mutations testing (performed by MD Anderson or a CLIA certified test offered by a commercial vendor such as Foundation One or Caris) that demonstrates a nonsynonymous PPP2R1A mutation (other protein phosphatase 2A or related pathway mutations/alterations may be eligible if approved by the PI). Synonymous mutations and variants of uncertain significance do not qualify.
- 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 platinum treatment (not applicable to the uterine serous carcinoma molecularly defined expansion cohort, however, subjects with uterine serous must have received at least one prior line of platinum-based therapy).
- Have measurable disease based on modified 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, CT, and 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.
You may not qualify if:
- 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 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 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 (\> 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, peripherally neuropathy).
- 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, ulcerative colitis).
- History of primary immunodeficiency.
- History of allogeneic organ transplant.
- History of hypersensitivity to Durvalumab, Tremelimumab, or any excipient.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Hinchcliff EM, Knisely A, Adjei N, Fellman B, Yuan Y, Patel A, Xu C, Westin SN, Sood AK, Soliman PT, Shafer A, Fleming ND, Gershenson DM, Vikram R, Bathala T, Vining D, Ganeshan DM, Lu KH, Sun CC, Meyer LA, Jazaeri AA. Randomized phase 2 trial of tremelimumab and durvalumab in combination versus sequentially in recurrent platinum-resistant ovarian cancer. Cancer. 2024 Apr 1;130(7):1061-1071. doi: 10.1002/cncr.35126. Epub 2023 Nov 27.
PMID: 38009662DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Amir A Jazaeri
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 10, 2017
First Posted
January 20, 2017
Study Start
May 18, 2017
Primary Completion
September 11, 2025
Study Completion
September 11, 2025
Last Updated
September 19, 2025
Record last verified: 2025-09