Patient case: 38-year-old male with Liposarcoma. Genetic variant: CDK4 Amplification. Other conditions: GERD.

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

Summary: 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.

Eligibility: 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

Relevance to patient case: not relevant