Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors
Condition: Carcinoid Tumor
MeSH terms: Carcinoid Tumor
Intervention: Ziv-aflibercept
Intervention MeSH terms: Aflibercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Progressive; Metastatic

Summary:

      This research study is a Phase II clinical trial, which tests the safety and effectiveness of
      an investigational drug to learn whether the drug works in treating a specific cancer.
      "Investigational" means that the drug, Ziv-aflibercept, is being studied. It also means that
      the FDA has not yet approved Ziv-aflibercept for use in patients with your type of cancer.

      Every person has molecules in their bloodstream called vascular endothelial growth factors
      (VEGFs). These molecules help grow and sustain new blood vessels needed by the human body.
      Cancer tumors hijack this mechanism because they need new blod vessels and oxygen to grow.
      Ziv-aflibercept is an antibody. Antibodies are proteins that are produced naturally in our
      bodies and help to recognize foreign substances in our body. Ziv-aflibercept is a "targeted
      therapy" called a "VEGF Trap", that "traps" (binds) these VEGFs and prevents the cancer from
      using them to grow.

      Though Ziv-aflibercept has not yet been FDA approved for the treatment of carcinoid tumors,
      it has recently been approved for patients with treatment-resistant colorectal cancer.

      In this research study, we will use Ziv-aflibercept in combination with standard octreotide
      therapy to see if it slows the growth or spread of your carcinoid tumor. Standard octreotide
      (sandostatin) therapy is currently approved for treating symptoms of carcinoid tumors, such
      as those caused by carcinoid syndrome. Carcinoid syndrome is caused by hormones and other
      substances released by carcinoid tumors into the bloodstream. One of these secreted
      substances is serotonin, one of the body's natural chemical messengers. When excess serotonin
      secreted by the carcinoid tumors reaches the body's tissues, it is thought to cause diarrhea
      and redness (flushing) of the face, chest or back. Excess serotonin may also cause changes in
      the structure of the heart valves, which can impair the heart's function. Octreotide works by
      binding to receptors found on carcinoid tumors and prevents the release of hormones from the
      tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed well differentiated or moderately differentiated
             neuroendocrine tumor from either a primary or metastatic site

          -  Must have disease that is not amenable to curative resection

          -  Must have evidence of disease progression within 12 months prior to study entry

          -  Must have measurable disease (RECIST 1.1)

          -  Prior chemoembolization of local ablative therapies are allowed, provided there is
             measurable disease outside of the area treated, or documented evidence of progression
             at the site of prior treatment

          -  No limit to number of prior treatments. Prior bevacizumab allowed unless discontinued
             due to unacceptable toxicity. Prior TKI targeting VEGF receptors allowed

          -  Treatment with a somatostatin analog required for all subjects

          -  Subjects with history of hypertension must be adequately controlled

          -  Therapeutic anticoagulation is allowed. Must be on a stable dose of anticoagulant
             medication

          -  Must agree to use adequate contraception prior to study entry, for the duration of
             study participation and for 3 months after last administration of study drug

        Exclusion Criteria:

          -  Prior treatment including chemoembolization within 4 weeks of study entry

          -  Major surgery within 4 weeks of study entry or minor surgery within 2 weeks of study
             entry

          -  Pregnant or breastfeeding

          -  Poorly differentiated carcinoma, high grade neuroendocrine tumor or small cell
             carcinoma

          -  Prior treatment with Ziv-aflibercept

          -  Pancreatic neuroendocrine tumor (islet cell carcinoma)will be excluded from this
             study. All non functional and functional islet cell carcinomas such as insulinoma,
             glucagonoma, gastrinoma, VIPoma will be excluded.

          -  Not adequately recovered from toxicity of previous therapy

          -  Known untreated brain or other central nervous system metastases

          -  Known allergy to any of the study agents or to compounds of similar chemical or
             biologic composition

          -  History of congestive heart failure

          -  Symptomatic peripheral arterial disease

          -  Unhealed wounds, ulcers or bone fractures

          -  HIV positive or active Hepatitis infection

          -  History of abdominal fistula, GI perforation, intra abdominal abscess, uncontrolled GI
             bleeding, diverticulitis within 6 months of study entry

          -  History of arterial thrombotic events such as myocardial infarction, unstable angina
             pectoris or any ischemic or hemorrhagic cerebrovascular accident within the past 6
             months

          -  No history of pulmonary embolism, DVT or vascular access related thrombosis if not
             also receiving adequate anticoagulation at a stable dose.

          -  No history of prior or synchronous malignancy except if treated with curative intent
             at least 3 years prior to study entry, or adequately treated non-melanoma skin cancer,
             cervical carcinoma in situ, or prostate intraepithelial neoplasia without evidence of
             prostate cancer

          -  Uncontrolled non-malignant illness that may increase the risks associated with study
             participation or may interfere with the conduct of the study or interpretation of
             study results

          -  Uncontrolled psychiatric illness or social situations that would limit compliance with
             study requirements