Nintedanib in Treating Patients With Locally Advanced or Metastatic Neuroendocrine Tumors
Condition: Carcinoid Tumor; Metastatic Carcinoid Tumor; Neuroendocrine Neoplasm
MeSH terms: Neoplasms; Carcinoid Tumor; Neuroendocrine Tumors
Intervention: Laboratory Biomarker Analysis; Nintedanib; Pharmacological Study; Quality-of-Life Assessment
Intervention description: Correlative studies; Given PO; Correlative studies; Ancillary studies
Intervention MeSH terms: Nintedanib; Tyrosine Protein Kinase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well nintedanib works in treating patients with
      neuroendocrine tumors that have spread from where they started to nearby tissue or lymph
      nodes (locally advanced) or have spread from the primary site (place where they started) to
      other places in the body (metastatic). Nintedanib may stop the growth of tumor cells by
      slowing or stopping a certain type of receptor called vascular endothelial growth factor
      receptor (VEGFR) from attaching to its target. This may stop the growth of neuroendocrine
      tumors by blocking the growth of new blood vessels necessary for tumor growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must be on a stable dose of octreotide (Sandostatin®) long-acting release
             (LAR) or lanreotide for 3 months prior to study enrollment

          -  Patient must have histologically or cytologically confirmed well differentiated or
             moderately differentiated (low grade or intermediate grade) neuroendocrine tumor that
             is locally advanced or metastatic and not of pancreatic origin

          -  Measurable disease determined by computed tomography (CT) or magnetic resonance
             imaging (MRI)

          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Life expectancy greater than 3 months

          -  Leukocytes >= 3,000/uL

          -  Absolute neutrophil count >= 1,500/uL

          -  Total bilirubin =< 2 mg/dL

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x upper limit
             of normal (ULN) and bilirubin =< ULN for patients without liver metastases

          -  AST/ALT =< 2.5 x ULN and bilirubin =< ULN for patients with liver metastases

          -  Patients with Gilbert syndrome and bilirubin < 2 x ULN and normal AST/ALT

          -  Creatinine =< 1.5 mg/dl

          -  Prior treatment will be permitted including surgery (>= 4 weeks), cytotoxic
             chemotherapy (maximum of 2 prior regimens); radiation, interferon, targeted growth
             factors (>= 4 weeks); and prior treatment with octreotide, will be allowed

          -  Ability to swallow and retain oral medication

          -  Participants of child-bearing potential (both male and female) 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

          -  Participant or legal representative 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

          -  Archival tissue of carcinoid biopsy must be available

        Exclusion Criteria:

          -  Uncontrolled hypertension, unstable angina, New York Heart Association grade II or
             greater congestive heart failure, unstable symptomatic arrhythmia requiring
             medication, or clinically significant peripheral vascular disease (grade II or
             greater)

          -  Presence of brain metastases

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to day 0, or anticipated need for major surgical procedure during the course of
             the study, or fine needle aspirations or core biopsies within 7 days prior to day 0

          -  Significant proteinuria at baseline (>= 500 mg/24 hours [h])

          -  Serious non-healing wound, ulcer or bone fracture

          -  Evidence of bleeding diathesis or coagulopathy

          -  Recent (=< 6 months) arterial thromboembolic events, including transient ischemic
             attack, cerebrovascular accident, unstable angina, or myocardial infarction

          -  Poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma,
             adenocarcinoid, goblet cell carcinoma, or small cell carcinoma

          -  Hepatic artery embolization or ablation of hepatic metastasis within 3 months of
             enrollment, prior peptide receptor radionuclide therapy (PRRT) within 4 months or any
             other cancer therapy within 4 weeks (as long as all toxicities are resolved)

          -  Intolerance or hypersensitivity to octreotide

          -  Severe or uncontrolled medical conditions

          -  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