Clinical Trials /

A Study of Durvalumab With or Without Tremelimumab in Endometrial Cancer

NCT03015129

Description:

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.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Durvalumab With or Without Tremelimumab in Endometrial Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 16-1491
  • NCT ID: NCT03015129

Conditions

  • Endometrial Cancer
  • Endometrial Carcinosarcoma
  • Endometrial Carcinoma
  • Endometrial Cancer Recurrent
  • Endometrial Carcinoma, Recurrent

Interventions

DrugSynonymsArms
DurvalumabDurvalubmab
TremelimumabDurvalubmab + Tremelimumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
DurvalubmabExperimentalPatients will receive intravenous infusion of durvalumab 1500mg Fixed Dose every 4 weeks until patient develops a loss of clinical benefit or experiences unacceptable toxicities.
  • Durvalumab
Durvalubmab + TremelimumabExperimentalPatients 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.
  • Durvalumab
  • Tremelimumab

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.

          -  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 1.1 (Section 8.1). 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 1.

          -  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, one 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:

               -  Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)

               -  Platelet ≥ 100 x 10^9/L (>100,000 per mm^3)

               -  Hemoglobin ≥ 9.0 g/dL

               -  Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (Unless
                  Gilbert's Syndrome, without concurrent clinically significant liver disease)

               -  AST (SGOT)/ALT (SGPT) ≤ 3 x institutional upper limit of normal unless (ULN)
                  liver metastases are present, in which case it must be ≤ 5x ULN

               -  Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)

          -  Female subjects must either be of non-reproductive potential (ie, 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 follow
             up.

          -  Patients must have been enrolled, or agree to consent to the companion genomic
             profiling study MSKCC IRB# 12-245. Results must be available before starting
             treatment on protocol.

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal information.

        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.

          -  At least 4 weeks must have elapsed since the patient underwent any major surgery
             (e.g., major: laparotomy, laparoscopy) There is no delay in treatment for minor
             procedures (e.g., central venous access catheter placement).

          -  Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3
             electrocardiograms (ECGs)

          -  Current or prior use of immunosuppressive medication within 28 days before the first
             dose of durvalumab or durvalumab and 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. Patients
             who have received acute, low dose, systemic immunosuppressant medications (e.g.,
             dexamethasone for nausea or steroids as CT scan contrast premedication) may be
             enrolled.

          -  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 and/or confirmed pneumonitis or interstitial lung disease

          -  History of allogeneic organ transplant

          -  History of hypersensitivity to durvalumab or any excipient

          -  History of hypersensitivity to tremelimumab

          -  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

          -  Receipt of live attenuated vaccination within 30 days prior to study entry or within
             30 days of receiving durvalumab or tremelimumab.

          -  Any condition that, in the opinion of the investigator, would interfere with
             evaluation of study treatment or interpretation of patient safety or study results

          -  Symptomatic or uncontrolled brain metastases requiring concurrent treatment,
             inclusive of but not limited to surgery, radiation and/or corticosteroids.

          -  Subjects with uncontrolled seizures.

          -  Patients who are pregnant or breastfeeding or patients of reproductive potential 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

          -  History of small or large bowel obstruction within 3 months of registration,
             including subjects with palliative gastric drainage catheters. Subjects with
             palliative diverting ileostomy or colostomy are allowed if they have been
             symptom-free for more than 3 months.

          -  Ongoing bowel perforation or presence of bowel fistula or abscess within 3 months of
             registration.

          -  Subjects with refractory ascites, defined as ascites needing drainage catheter or
             therapeutic paracentesis more often than every 4 weeks.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment Efficacy determined by measuring the Overall Response Rate
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Durvalumab
  • MEDI4736
  • Tremelimumab
  • anti-PD-L1 Antibody
  • anti-CTLA-4 antibody
  • 16-1491

Last Updated

April 3, 2017