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Gastric Cancer Clinical Trials

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SLUHN 2016-32

A Phase III open-label, multicenter trial of maintenance therapy with avelumab (MSB0010718C) versus continuation of first-line chemotherapy in subjects with unresectable, locally advanced or metastatic, adenocarcinoma of the stomach, or of the gastro-esophageal junction

  • Physician & Study Coordinator
  • Synopsis
  • Inclusion Criteria
  • Exclusion Criteria
  • Physician

    Asim Ali, MD

    Study Coordinator

    Jillian Timer, RN, BSN
    484-503-4156

    Jillian.Timer@sluhn.org
  • Treatment Agent: Avelumab

    Synopsis: The study drug is an investigational drug that is being evaluated for the treatment of patients with stomach cancer or gastro-esophageal junction cancer (the point where your food pipe [esophagus] joins your stomach) that is unresectable (inoperable), locally advanced (the cancer has spread to nearby tissue) or has metastasized (the cancer has spread to other parts of the body).

    This clinical research study will look at the safety and effectiveness of the study drug compared with continuing chemotherapy in patients who receive 12-weeks of initial chemotherapy. If the initial chemotherapy does not work well for you, your participation in the study will end and the study doctor will discuss your treatment options with you. However, if the chemotherapy does work well for you, you will enter the next part of the study. You will then receive either the study drug or continuation of the same chemotherapy until the cancer grows or spreads.

    The study also has an optional pharmacogenetic research part. Pharmacogenetic research is an important way to try to understand the role of genetics in human disease and how genes impact the effectiveness of drugs, because differences in genes can change the way a person responds to a particular drug.

    • Has read, understood and signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management
    • Male or female subjects aged ≥ 18 years
    • Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or a minimum number of 7 (preferably 10) unstained tumor slides suitable for PD-L1 expression assessment
    • Disease must be measurable by RECIST v1.1
    • Subjects with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or GEJ
    • ECOG PS of 0 to 1 at trial entry
    • Estimated life expectancy of more than 12 weeks
    • Adequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused)
    • Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects
    • Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
    • Negative blood pregnancy test at Screening for women of childbearing potential. For the purposes of this trial, women of childbearing potential are defined as: “All female subjectsafter puberty unless they are post-menopausal for at least 2 years, are surgically sterile or are sexually inactive.”
    • Highly effective contraception (i.e. methods with a failure rate of less than 1 % per year) for both male and female subjects if the risk of conception exists (Note: The effects of the trial treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use highly effective contraception, defined in Appendix II Guidance on Contraception or as stipulated in national or local guidelines. Highly effective contraception must be used 28 days prior to first trial treatment administration, for the duration of trial treatment, and at least for 60 days after stopping trial treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately.)
    • Prior therapy with any antibody or drug targeting T-cell coregulatory proteins (immune checkpoints) such as PD-1, PD-L1, or cytotoxic T-lymphocyte antigen-4 (CTLA-4).
    • Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy [with the exception of palliative bone-directed radiotherapy], immune therapy, or cytokine therapy, except for erythropoietin)
    • Prior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or GEJ
    • Tumor shown to be HER2+ by immunohistochemistry (IHC > 2+) and/or by fluorescence in situ hybridization (FISH).
    • Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the subject has not fully recovered from the surgery within 4 weeks of enrolment
    • Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to < 10 mg prednisone daily). Note:
      • Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before first dose of trial treatment
      • Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤ 10 mg per day of equivalent prednisone
    • All subjects with brain metastases, except those meeting the following criteria:
      • Brain metastases have been treated locally, and
      • 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)
    • Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, colorectal, breast)
    • Prior organ transplantation, including allogeneic stem-cell transplantation
    • Significant acute or chronic infections including, among others:
      • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
      • Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive).
      • Active tuberculosis (history of exposure or history of positive TB test; plus presence of clinical symptoms, physical or radiographic findings)
    • 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 NCI-CTCAE 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 > 2 NCI-CTCAE v 4.03 except alopecia
    • Neuropathy Grade > 3.
    • Pregnancy or lactation
    • Known alcohol or drug abuse
    • History of uncontrolled intercurrent illness including but not limited to:
      • Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmHg or lower)
      • or, uncontrolled active infection,
      • or, uncontrolled diabetes (e.g., hemoglobin A1c ≥ 8%)
    • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident / stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina pectoris, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious cardiac arrhythmia requiring medication (including QTc prolongation of > 470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome
    • All other significant diseases (for example, inflammatory bowel disease), 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 and that would limit compliance with study requirements
    • Vaccination within 55 days (5 half-lives x 127 hours + 30 days) of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines)
    • Legal incapacity or limited legal capacity