Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin
Condition: Locally Advanced Digestive System Neuroendocrine Carcinoma; Locally Advanced Pancreatic Neuroendocrine Carcinoma; Metastatic Digestive System Neuroendocrine Carcinoma; Metastatic Pancreatic Neuroendocrine Carcinoma; Refractory Digestive System Neuroendocrine Carcinoma; Refractory Pancreatic Neuroendocrine Carcinoma; Unresectable Digestive System Neuroendocrine Carcinoma; Unresectable Pancreatic Neuroendocrine Carcinoma
MeSH terms: Carcinoma; Carcinoma, Neuroendocrine; Carcinoma, Islet Cell
Intervention: Fluorouracil; Leucovorin; Liposomal Irinotecan; Quality-of-Life Assessment
Intervention description: Given IV; Given IV; Given IV; Correlative studies
Intervention MeSH terms: Leucovorin; Fluorouracil; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well liposomal irinotecan, leucovorin, and fluorouracil work
      in treating patients with high grade neuroendocrine cancer of gastrointestinal, unknown, or
      pancreatic origin that does not respond to treatment and has spread to other places in the
      body. Lliposomal irinotecan may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and
      leucovorin, 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 liposomal
      irinotecan, leucovorin and fluorouracil may work better in treating patients with
      neuroendocrine cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must have a locally advanced and unresectable or metastatic
             gastroenteropancreatic neuroendocrine carcinoma of the gastrointestinal (GI) tract,
             pancreas, or of other known or unknown primary site where 5FU based therapy would be
             considered reasonable by the treated MD, lung primary is excluded. Patients may have
             either progressed on therapy or within 6 months of completing therapy, or be
             intolerant of therapy to be considered eligible.

          -  Participant must have tissue available for central pathology review and, must have
             pathologically/histologically confirmed high grade neuro endocrine defined as Ki-67
             proliferative index of 20-100% or, must have evidence of at least 10 mitotic figures
             per 10 high powered fields.

          -  Comprehensive Genomic Profiling will be performed on archival tissue available prior
             to enrollment. If no archival tissue is available, then patient must have fresh biopsy
             prior to treatment administration if clinically indicated.

          -  Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.

          -  Leukocytes >= 3,000/mm^3 .

          -  Absolute neutrophil count >= 1,500/mm^3.

          -  Hemoglobin >= 9 g/dL.

          -  Platelets >= 100,000/mm^3.

          -  Total bilirubin =< institutional upper limit of normal (ULN) or =< 1.5 x institutional
             ULN (if the patient has liver metastases.

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional ULN or (=< 5 x institutional ULN if the patient has liver
             metastases).

          -  Serum creatinine =< 1.5 x institutional ULN or measured or calculated creatinine
             clearance by Cockcroft Gault Equation >= 50ml/min for subjects with creatinine levels
             > 1.5 x ULN.

          -  Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
             criteria present.

          -  Participant must have a life expectancy of >= 12 weeks as determined clinically by the
             treating physician.

          -  Participants of child-bearing potential must agree to use adequate contraceptive
             methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study
             entry. Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately.

               -  A female of childbearing potential is any woman, regardless of sexual orientation
                  or whether they have undergone tubal ligation, who meets the following criteria:
                  1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
                  naturally postmenopausal for at least 24 consecutive months (i.e., has had menses
                  at any time in the preceding 24 consecutive months).

               -  Women of childbearing potential and sexually active males must be strongly
                  advised to use an accepted and effective method of contraception or to abstain
                  from sexual intercourse for the duration of their participation in the study.

          -  Participant must understand the investigational nature of this study and sign an
             Independent Ethics Committee/Institutional Review Board approved written informed
             consent form prior to receiving any study related procedure.

        Exclusion Criteria:

          -  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 for at least four weeks prior to
             the first dose of trial treatment and any neurologic symptoms have returned to
             baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  Participants with known dihydropyrimidine dehydrogenase (DPD) deficiency.

          -  Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

          -  Known hypersensitivity to any of the components of Nal-IRI, other liposomal products,
             fluoropyrimidines or leucovorin.

          -  Investigational therapy administered within 4 weeks, or within a time interval less
             than at least 5 half-lives of the investigational agent, whichever is longer, prior to
             the first scheduled day of dosing in this study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant or nursing female participants.

          -  Unwilling or unable to follow protocol requirements.

          -  Any condition which in the Investigator?s opinion deems the participant an unsuitable
             candidate to receive study drug.