Clinical Trials /

Avelumab and Trabectedin in Treating Patients With Liposarcoma or Leiomyosarcoma That is Metastatic or Cannot Be Removed by Surgery

NCT03074318

Description:

This phase I/II studies the side effects of avelumab and trabectedin and how well they work in treating patients with leiomyosarcoma or liposarcoma that has spread to other places in the body (metastatic) or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving avelumab and trabectedin may work better in treating patients with liposarcoma or leiomyosarcoma.

Related Conditions:
  • Leiomyosarcoma
  • Liposarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Avelumab and Trabectedin in Treating Patients With Liposarcoma or Leiomyosarcoma That is Metastatic or Cannot Be Removed by Surgery
  • Official Title: A Phase I/II Trial Combining Avelumab and Trabectedin for Advanced Liposarcoma and Leiomyosarcoma

Clinical Trial IDs

  • ORG STUDY ID: 9717
  • SECONDARY ID: NCI-2017-00234
  • SECONDARY ID: 9717
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03074318

Conditions

  • Metastatic Leiomyosarcoma
  • Metastatic Liposarcoma

Interventions

DrugSynonymsArms
AvelumabMSB0010718CTreatment (avelumab, trabectedin)
TrabectedinEcteinascidin, Ecteinascidin 743, ET-743, YondelisTreatment (avelumab, trabectedin)

Purpose

This phase I/II studies the side effects of avelumab and trabectedin and how well they work in treating patients with leiomyosarcoma or liposarcoma that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as avelumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as trabectedin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving avelumab and trabectedin may work better in treating patients with liposarcoma or leiomyosarcoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the safety and tolerability of the combination of trabectedin and avelumab in
      patients with advanced leiomyosarcoma and liposarcomas (L-type sarcomas).

      II. To assess the objective response rate of advanced L-type sarcoma patients receiving the
      combination of avelumab and trabectedin.

      SECONDARY OBJECTIVES:

      I. To explore the clinical activity of avelumab and trabectedin with respect to time to
      response.

      II. To explore the clinical activity of avelumab and trabectedin with respect to duration of
      response.

      III. To explore the clinical activity of avelumab and trabectedin with respect to
      progression-free survival (PFS) at 12 weeks.

      IV. To explore the clinical activity of avelumab and trabectedin with respect to clinical
      benefit rate (complete response [CR]+ partial response [PR]+ stable disease [SD]) at 12
      weeks.

      V. To explore the clinical activity of avelumab and trabectedin with respect to overall
      survival.

      OUTLINE:

      Patients receive avelumab intravenously (IV) over 1 hour on day 1. Courses repeat every 14
      days in the absence of disease progression or unacceptable toxicity. Patients also receive
      trabectedin IV over 24 hours on day 1. Courses repeat every 3 weeks and may repeat up to
      every 5 weeks after 2 courses in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 12 weeks for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (avelumab, trabectedin)ExperimentalPatients receive avelumab IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients also receive trabectedin IV over 24 hours on day 1. Courses repeat every 3 weeks and may repeat up to every 5 weeks after 2 courses in the absence of disease progression or unacceptable toxicity.
  • Avelumab
  • Trabectedin

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosed with advanced (metastatic or unresectable) leiomyosarcoma or liposarcoma

          -  Being considered for trabectedin as standard of care

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

          -  Platelet count >= 100 x 10^9/L

          -  Hemoglobin >= 9 g/dL (may have been transfused)

          -  Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range

          -  Aspartate aminotransferase (AST) levels =< 2.5 x ULN for all subjects

          -  Creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula

          -  Ejection fraction > 45%

          -  Negative serum pregnancy test at screening for women of childbearing potential

          -  Highly effective contraception for both male and female subjects if the risk of
             conception exists; women of childbearing potential and men able to father a child
             must agree to use 2 methods of highly effective contraception, defined as methods
             with a failure rate of less than 1 % per year; highly effective contraception is
             required at least 28 days prior, throughout and for at least 60 days after avelumab
             treatment and 5 months following the last dose of trabectedin

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky
             performance scale >= 70

        Exclusion Criteria:

          -  All subjects with brain metastases, except those meeting the following criteria:

               -  Brain metastases that have been treated locally and are clinically stable for at
                  least 2 weeks prior to enrollment

               -  No ongoing neurological symptoms that are related to the brain localization of
                  the disease (sequelae that are a consequence of the treatment of the brain
                  metastases are acceptable)

               -  Subjects must be either off steroids or on a stable or decreasing dose of =< 10
                  mg daily prednisone (or equivalent)

          -  Prior organ transplantation, including allogeneic stem cell transplantation

          -  Prior treatment with trabectedin

          -  Significant acute or chronic infections including, among others:

               -  Known history of testing positive test for human immunodeficiency virus (HIV) or
                  known acquired immunodeficiency syndrome (AIDS)

               -  Positive test for hepatitis B virus (HBV) surface antigen and/or confirmatory
                  hepatitis C virus (HCV) ribonucleic acid (RNA) (if anti-HCV antibody tested
                  positive)

          -  Active autoimmune disease that might deteriorate when receiving an immunostimulatory
             agent:

               -  Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid
                  disease not requiring immunosuppressive treatment are eligible

               -  Subjects requiring hormone replacement with corticosteroids are eligible if the
                  steroids are administered only for the purpose of hormonal replacement and at
                  doses =< 10 mg or 10 mg equivalent prednisone per day

               -  Administration of steroids through a route known to result in a minimal systemic
                  exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable

          -  Known severe hypersensitivity reactions to monoclonal antibodies (grade >= 3 National
             Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version
             [v] 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more
             features of partially controlled asthma)

          -  Persisting toxicity related to prior therapy of grade > 1 NCI-CTCAE v 4.03; however,
             alopecia and sensory neuropathy grade =< 2 is acceptable

          -  Pregnancy or lactation

          -  Known alcohol or drug abuse

          -  All other significant diseases (for example, inflammatory bowel disease, uncontrolled
             asthma), which, in the opinion of the investigator, might impair the subject's
             tolerance of trial treatment

          -  Any psychiatric condition that would prohibit the understanding or rendering of
             informed consent

          -  Any vaccination within 4 weeks of the first dose of avelumab

          -  Clinically significant cardiovascular disease including cerebral vascular
             accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
             prior to enrollment), congestive heart failure with New York Heart Association [NYHA]
             class II or greater or serious cardiac arrhythmia requiring medication

          -  Severe (requiring active treatment) acute or chronic medical conditions including:
             colitis, inflammatory bowel disease, pneumonitis, or pulmonary fibrosis

          -  Recent (within the past year) or active suicidal ideation or behavior
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 30 days
Safety Issue:
Description:Measured by Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4.03

Secondary Outcome Measures

Measure:Time to response
Time Frame:Up to 2 years
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors 1.1
Measure:Duration of response
Time Frame:Up to 2 years
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors 1.1
Measure:Progression-free survival
Time Frame:At 12 weeks
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors 1.1
Measure:Complete response rate (CR)
Time Frame:At 12 weeks
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors 1.1
Measure:Partial response rate (PR)
Time Frame:At 12 weeks
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors 1.1
Measure:Stable disease (SD)
Time Frame:At 12 weeks
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors 1.1
Measure:Clinical benefit rate (percentage of patients who achieve CR+PR+SD)
Time Frame:At 12 weeks
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors 1.1
Measure:Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors 1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

Last Updated

March 3, 2017