Clinical Trials /

Durvalumab and Tremelimumab in Treating Participants With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

NCT03026062

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab and Tremelimumab in Treating Participants With Recurrent or Refractory Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
  • Official Title: Randomized Phase II Trial of Durvalumab (MEDI4736) and Tremelimumab Administered in Combination Versus Sequentially in Recurrent Platinum-Resistant Epithelial Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2016-0093
  • SECONDARY ID: NCI-2018-01240
  • SECONDARY ID: 2016-0093
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03026062

Conditions

  • Platinum-Resistant Fallopian Tube Carcinoma
  • Platinum-Resistant Ovarian Carcinoma
  • Platinum-Resistant Primary Peritoneal Carcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Refractory Fallopian Tube Carcinoma
  • Refractory Ovarian Carcinoma
  • Refractory Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Arm I (sequential tremelimumab, durvalumab)
TremelimumabAnti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, TicilimumabArm I (sequential tremelimumab, durvalumab)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the median immune-related progression-free survival (irPFS) in the
      experimental arms.

      SECONDARY OBJECTIVES:

      I. To determine the rate of grade III or higher treatment related toxicity in each
      experimental arm.

      II. To describe the immunological and gene expression changes induced by tremelimumab and the
      combination of tremelimumab and durvalumab in epithelial ovarian cancer (EOC) tumor tissues
      and blood.

      III. To determine the median overall survival (OS), objective response rate (ORR), and irPFS
      rate at 10 months.

      IV. To determine the proportion of patients that discontinue treatment due to side effects.

      EXPLORATORY OBJECTIVES:

      I. To determine second progression-free survival (PFS) (PFS2) following initial progression
      in each arm.

      II. To determine the response rate to durvalumab (MEDI4736) following treatment with
      tremelimumab (in the sequential arm).

      III. To evaluate the patient reported symptom burden in each experimental arm.

      OUTLINE: Participants are randomized to 1 of 2 arms.

      ARM I (SEQUENTIAL): Participants receive tremelimumab intravenously (IV) over 60 minutes on
      day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or
      unacceptable toxicity. Participants then receive durvalumab IV over 60 minutes on day 1.
      Treatment repeats every 4 weeks for 9 courses in the absence of disease progression or
      unacceptable toxicity.

      ARM II (COMBINATION): Participants receive tremelimumab IV and durvalumab IV over 60 minutes
      on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression
      or unacceptable toxicity. Participants then receive durvalumab IV on day 1. Treatment repeats
      every 4 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

      After study treatment, participants are followed up at 30 days and then every 2 months
      thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (sequential tremelimumab, durvalumab)ExperimentalParticipants receive tremelimumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Participants then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
  • Durvalumab
  • Tremelimumab
Arm II (combination tremelimumab, durvalumab)ExperimentalParticipants receive tremelimumab IV and durvalumab IV over 60 minutes on day 1. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Participants then receive durvalumab IV on day 1. Treatment repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
  • Durvalumab
  • Tremelimumab

Eligibility Criteria

        Inclusion Criteria:

          -  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
             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 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
             platinum treatment.

          -  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.

        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 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,
             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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune-related progression-free survival (irPFS)
Time Frame:Up to 4 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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