A Phase 2 Trial of Durvalumab [MEDI4736](Anti-PD-L1 Antibody) With or Without Tremelimumab (Anti-CTLA-4 Antibody) in Patients With Persistent or Recurrent Endometrial Carcinoma and Endometrial Carcinosarcoma
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Endometrial Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 80
- Locations
- 7
- Primary Endpoint
- Treatment Efficacy Determined by Measuring the Overall Response Rate
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This study will test the safety and efficacy of the experimental drug called durvalumab with or without another experimental drug called tremelimumab in endometrial cancer.
Radiologic tumor assessment will be repeated every 8 weeks +/- 7 days for the first 48 weeks and then every 12 weeks +/- 7 days until PD. For patients who remain progression free 2 years post completion of protocol directed treatment, every 6 months +/- 1 month. irRECIST assessments will only be completed for patients continuing treatment beyond PD.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must have recurrent or persistent endometrial carcinoma (including: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma) or endometrial carcinosarcoma). Histologic documentation of diagnosis of carcinoma is required. MSI-high patients will be identified based on immunohistochemistry or MSI testing of archival tumor specimens by department of pathology or via known mutations found in mismatch repair genes via the Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay through MSKCC IRB# 12-
- •All patients must have measurable disease. Measurable disease is defined by RECIST (version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.
- •Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.
- •Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
- •Age ≥ 18 years and life expectancy of ≥ 12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Resolution of (non-laboratory) adverse effects of recent surgery, radiotherapy, or chemotherapy to Grade ≤1 prior to first study treatment (with the exception of alopecia or neuropathy).
- •Patients must have had one prior platinum-based chemotherapeutic regimen for management of endometrial carcinoma or carcinosarcoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen.
- •Patients are allowed to receive, but are not required to receive, three additional cytotoxic regimen for management of recurrent or persistent disease. Hormonal therapies will not count toward the prior regimen limit.
- •Adequate normal organ and marrow function defined by the following laboratory results obtained within 14 days prior to first treatment:
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site); Previous enrollment in the present study.
- •Participation in another clinical study with receipt of an investigational product during the last 4 weeks
- •Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab or any anti-CTLA4, including tremelimumab.
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease ≥3 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
- •Adequately treated carcinoma in situ without evidence of disease (eg, cervical cancer in situ)
- •Adequately treated stage 1 breast cancer.
- •Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) \< 21 days prior to the first dose of study drug. Receipt of the last dose of hormonal therapy within \< 7 days prior to the first dose of study drug.
- •Any prior radiation therapy must be discontinued at least four weeks prior to registration.
Arms & Interventions
Durvalubmab
Patients will receive intravenous infusion of durvalumab 1500mg Fixed Dose every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.
Intervention: Durvalumab
Durvalubmab + Tremelimumab
Patients will receive 1500mg Flat Dose durvalubmab via intravenous infusion every 4 weeks for up to 4 cycles and 75mg tremelimumab via intravenous infusion every 4 weeks for up to 4 cycles, and then continue 1500mg Fixed Dose durvalumab every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.
Intervention: Durvalumab
Durvalubmab + Tremelimumab
Patients will receive 1500mg Flat Dose durvalubmab via intravenous infusion every 4 weeks for up to 4 cycles and 75mg tremelimumab via intravenous infusion every 4 weeks for up to 4 cycles, and then continue 1500mg Fixed Dose durvalumab every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.
Intervention: Tremelimumab
Outcomes
Primary Outcomes
Treatment Efficacy Determined by Measuring the Overall Response Rate
Time Frame: Up to 72 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR