Perioperative Chemo and Pembrolizumab in Gastric Cancer
Condition: Gastric Cancer; Adenocarcinoma of the Gastroesophageal Junction
MeSH terms: Adenocarcinoma; Stomach Neoplasms
Intervention: Pembrolizumab; Standard of care chemotherapy regimen
Intervention description: Pembrolizumab dosed IV at 200mg every 21 days per cycle.; Standard regimen containing at least a platinum and Fluorouracil (5-FU) agent (per National Comprehensive Cancer Network guidelines) - such as Doublet or Triplet chemotherapy with capecitabine, oxaliplatin, and epirubicin (optional) (21 day cycle). Epirubicin can be excluded at the discretion of the treating physician.
Example:
Oxaliplatin dosed IV at 130 mg/m2 every 21 days per cycle. Capecitabine dosed orally at 625mg/m2 twice a day daily.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pembrolizumab; adenocarcinoma; gastric cancer; Locoregional gastric adenocarcinoma; Locoregional GE junction adenocarcinoma

Summary:

      This is a non-randomized, multi-site, open-label trial of pembrolizumab and chemotherapy in
      subjects with gastric or gastroesophageal (GE) junction adenocarcinoma. The purpose of this
      study is to determine and evaluate the efficacy of combination therapy with immune checkpoint
      blockade and chemotherapy used in the perioperative period in eradicating micrometastatic
      disease; and to compare paired tissue and serum samples (pre-treatment and post-treatment)
      from individually treated patients to explore the immune effects of combination therapy and
      predictors of response.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Have previously untreated localized gastric or GE junction adenocarcinoma as defined
             by T2 or greater primary lesion or the presence of any positive nodes- N+(clinical
             nodes) without evidence of metastatic disease.

          2. Plan to proceed to surgery following peri-operative chemotherapy based on standard
             staging studies per local practice.

          3. Be willing and able to provide written informed consent/assent for the trial. The
             subject may also provide consent for Future Biomedical Research. However, the subject
             may participate in the main trial without participating in Future Biomedical Research.

          4. Be at least 18 years of age on day of signing informed consent.

          5. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on Day 1.

          6. Have a performance status of 0 or 1 on the ECOG Performance Scale.

          7. Demonstrate adequate organ function as defined below, all screening labs should be
             performed within 14 days of treatment initiation.

             Adequate Organ Function Laboratory Values

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Platelets ≥100,000 / mcL

               -  Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7
                  days of assessment)

               -  Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be
                  used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60
                  mL/min for subject with creatinine levels > 1.5 X institutional ULN

               -  Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with
                  total bilirubin levels > 1.5 ULN

               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver
                  metastases

               -  Albumin >2.5 mg/dL

               -  International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
                  subject is receiving anticoagulant therapy as long as PT or PTT is within
                  therapeutic range of intended use of anticoagulants

               -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
                  of intended use of anticoagulants

               -  Creatinine clearance should be calculated per institutional standard.

          8. Have a 2D Echocardiogram with left ventricular ejection fraction = or > 45% in order
             to receive Epirubicin. Subjects with inadequate EF or other contraindication can
             proceed on study without the use of Epirubicin.

          9. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

         10. Female subjects of childbearing potential must be willing to use an adequate method of
             contraception - Contraception, for the course of the study through 120 days after the
             last dose of study medication.

             Note: Abstinence is acceptable if this is the usual lifestyle and preferred
             contraception for the subject.

         11. Male subjects of childbearing potential must agree to use an adequate method of
             contraception - Contraception, starting with the first dose of study therapy through
             120 days after the last dose of study therapy.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment. The use of physiologic doses of corticosteroids (prednisone 10 mf or
             equivalent) may be approved after consultation.

          3. Has a known history of active TB (Bacillus Tuberculosis)

          4. Hypersensitivity to pembrolizumab or any of its excipients.

          5. Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy
             for their current diagnosis.

          6. Has a known additional malignancy that is progressing or requires active treatment
             within 3 years from registration. Exceptions include basal cell carcinoma of the skin
             or squamous cell carcinoma of the skin that has undergone potentially curative therapy
             or in situ cervical cancer. Subjects with a history of prior malignancy diagnosed and
             treated greater than 3 years form registration may be considered with consultation of
             the primary investigator.

          7. Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          8. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          9. Has known history of prior pneumonitis requiring treatment with steroids, or any
             evidence of active, non-infectious pneumonitis.

         10. Has an active infection requiring systemic therapy which is not expected to have
             resolved by Cycle 1 Day 1 dosing.

         11. Has a history or current evidence of any condition (e.g. known deficiency of the
             enzyme dihydropyrimidine dehydrogenase [DPD]),, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         12. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         13. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

         14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

         15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

         17. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or
             child) who is investigational site or sponsor-investigator staff directly involved
             with this trial, unless prospective IRB approval (by chair or designee) is given
             allowing exception to this criterion for a specific subject.

         18. Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.