Pembrolizumab in Treating Patients With Small Bowel Adenocarcinoma That is Metastatic or Locally Advanced and Cannot Be Removed by Surgery
Condition: Metastatic Small Intestinal Adenocarcinoma; Recurrent Small Intestinal Carcinoma; Unresectable Small Intestinal Carcinoma
MeSH terms: Carcinoma; Adenocarcinoma
Intervention: Laboratory Biomarker Analysis; Pembrolizumab
Intervention description: Correlative studies; Given IV
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pembrolizumab works in treating patients with small
      bowel adenocarcinoma that has spread to other places in the body or that cannot be removed by
      surgery. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of
      tumor cells to grow and spread.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have biopsy-proven adenocarcinoma of the small bowel at any site
             (duodenum, jejunum, ileum), excluding ampullary and appendiceal tumors

          -  Have locally advanced (unresectable) or metastatic small bowel adenocarcinoma

          -  Willing and able to provide written informed consent for the trial

          -  Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

          -  Had at least one prior line of systemic chemotherapy for metastatic disease; adjuvant
             therapy would not count toward first-line therapy unless patient recurs less than 6
             months after completion of that regimen

          -  Willing to provide blood and tissue (can be archival) samples for mandatory research
             purposes

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (1.50 x 10^9 /L) obtained =< 28 days
             prior to registration

          -  Platelet count >= 100,000/mm^3 (100 x 10^9 /L) obtained =< 28 days prior to
             registration

          -  Hemoglobin >= 9.0 g/dL (5.6 mmol/L or 90 g/L) without transfusion or erythropoietin
             (EPO) dependency (within 7 days of assessment) obtained =< 28 days prior to
             registration

          -  Serum total bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN
             for subjects with total bilirubin levels > 1.5 x ULN obtained =< 28 days prior to
             registration

          -  Aspartate transaminase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN OR =< 5 x
             ULN for subjects with liver metastases obtained =< 28 days prior to registration

          -  Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated
             creatinine clearance must be >= 60 mL/min for subjects with creatinine levels > 1.5 X
             ULN using the Cockcroft-Gault formula (glomerular filtration rate [GFR] >= 60 mL/min
             [1.0 mL/s/m^2] can also be used in place of creatinine or creatinine clearance [CrCl])
             obtained =< 28 days prior to registration

          -  Female subject of childbearing potential have a negative urine or serum pregnancy =< 7
             days prior to registration; if the urine test is positive or cannot be confirmed as
             negative, a serum pregnancy test will be required

               -  Note: female subjects of childbearing potential should be willing to use 2
                  methods of birth control or be surgically sterile, or abstain from heterosexual
                  activity for the course of the study through 120 days after the last dose of
                  study medication; subjects of childbearing potential are those who have not been
                  surgically sterilized or have not been free from menses for > 1 year; male
                  subjects should agree to use an adequate method of contraception starting with
                  the first dose of study therapy through 120 days after the last dose of study
                  therapy

        Exclusion Criteria:

          -  Non-adenocarcinoma histology

          -  Adenocarcinoma originating in the ampulla or appendix; (duodenal tumors that involve
             the ampulla but originate in the duodenum are eligible)

          -  Currently participating and receiving study therapy, or have participated in a study
             of an investigational agent and received study therapy, or used an investigational
             device =< 4 weeks of registration

          -  Diagnosis of immunodeficiency or be receiving systemic steroid therapy or any other
             form of immunosuppressive therapy =< 7 days prior to registration

          -  History of active TB (bacillus tuberculosis)

          -  Hypersensitivity to pembrolizumab or any of its excipients

          -  Any of the following:

               -  Prior anti-cancer monoclonal antibody (mAb) =< 4 weeks prior to registration

          -  Prior chemotherapy, targeted small molecule therapy, or radiation therapy =< 2 weeks
             prior to registration or who has not recovered to =< grade 1 or baseline from adverse
             events due to the previously administered agent

               -  Note: subjects with =< grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study

          -  Received major surgery =< 2 weeks prior to registration, subject must have recovered
             adequately from the toxicity and/or complications from the intervention prior to
             starting therapy

          -  Known additional malignancy that is progressing or requires active treatment or that
             may interfere with interpretation of response evaluation, in the judgment of the
             investigator

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis;
             subjects with previously treated brain metastases may participate provided they are
             stable (without evidence of progression by imaging =< 4 weeks prior to registration
             and any neurologic symptoms have returned to baseline), have no evidence of new or
             enlarging brain metastases, and are not using steroids =< 7 days prior to
             registration; this exception does not include carcinomatous meningitis which is
             excluded regardless of clinical stability

          -  Active autoimmune disease (including but not limited to: patients with a history of
             inflammatory bowel disease, including ulcerative colitis and Crohn?s disease, patients
             with a history of symptomatic disease [e.g., rheumatoid arthritis, systemic
             progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune
             vasculitis (e.g. Wegener?s granulomatosis)]; CNS or motor neuropathy considered of
             autoimmune origin [e.g., Guillain-Barre syndrome and myasthenia gravis, multiple
             sclerosis]) that has required systemic treatment in the past 2 years (i.e. with use of
             disease modifying agents, corticosteroids or immunosuppressive drugs); replacement
             therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy
             for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic
             treatment

          -  Known history of or any evidence of active, non-infectious pneumonitis

          -  Active infection requiring systemic therapy

          -  History or current evidence of any condition, 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

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial

          -  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

          -  Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or other
             immune checkpoint inhibitor (e.g. anti-CTLA4)

          -  History of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid RNA [qualitative] is
             detected)

          -  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