A Ph 2 Study of Fosbretabulin in Subjects w Pancreatic or Gastrointestinal Neuroendocrine Tumors w Elevated Biomarkers
Condition: Neuroendocrine Tumors
MeSH terms: Neuroendocrine Tumors
Intervention: fosbretabulin tromethamine
Intervention description: 60 mg/m2, IV on Day 1, 8 and 15 of a 3-week cycle; 3 cycles or until progression or unacceptable toxicity
Intervention MeSH terms: Fosbretabulin; Combretastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PNET; GI-NET; neuroendocrine; carcinoid

Summary:

      This study will investigate the safety, symptoms and biomarker response of subjects with
      biopsy-proven well-differentiated, low-to-intermediate-grade, unresectable, or metastatic
      pancreatic neuroendocrine tumors (PNETs) or or Gastrointestinal Neuroendocrine tumors
      (GI-NETs) with elevated biochemical markers who have relapsed during or after receiving prior
      standard of care therapies, including octreotide, chemotherapy or targeted therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to read, understand and provide written consent to participate in the study

          -  Age ≥ 18 years

          -  Biopsy-proven well-differentiated, low-to-intermediate-grade PNET or GI-NET with
             elevated (> ULN) biomarkers (serotonin, 5-hydroxyindoleacetic acid (5-HIAA),
             chromogranin A (CgA), neurokinin A, and neuron-specific enolase (NSE))

          -  Life expectancy > 12 weeks

          -  Must have received or may still be receiving one or more therapies including
             octreotide or serotonin synthesis inhibitor (SSI) or other somatostatin analogues

          -  Confirmed progressive disease within 18 months of enrollment on study

          -  Recovered from prior radiation therapy or surgery

          -  Eastern Cooperative Oncology Group (ECOG) performance score 0-2

          -  Absolute neutrophil count (ANC) ≥ 1,500/µL (without growth factors)

          -  Platelet count ≥ 100,000/µL

          -  Adequate renal function as evidenced by serum creatinine

             ≤ 2.0 mg/dL (177 µmol/L)

          -  Adequate hepatic function: serum total bilirubin ≤ 2X greater than the upper limit of
             normal (ULN) (≤ 3X ULN in subjects with liver metastases), aspartate aminotransferase)
             AST) / alanine aminotransferase (AST) ≤ 2X the ULN for the local reference lab (≤ 5X
             the ULN for subjects with liver metastases)

          -  Disease that can be assessed (evaluable) with imaging (CT, MRI, PET, radionuclide
             imaging or other imaging modality)

          -  Women of childbearing potential as well as fertile men and their partners must use an
             effective method of birth control

        Exclusion Criteria:

          -  Inadequately controlled hypertension defined as BP > 150/100 mm Hg despite medication

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  Recent history (within 6 months of start of screening) of unstable angina pectoris
             pattern, myocardial infarction (including non-Q wave MI), or NYHA (New York Heart
             Association) Class III and IV Congestive Heart Failure (CHF)

          -  Subjects who have clinical evidence of carcinoid-induced heart disease

          -  History of prior cerebrovascular accident (CVA), including transient ischemic attach
             (TIA)

          -  Known central nervous system (CNS) disease except for treated brain metastasis

          -  History of torsade de pointes, ventricular tachycardia or fibrillation, pathologic
             sinus bradycardia (<60 bpm), heart block (excluding 1st degree block, being PR
             interval prolongation only), congenital long QT syndrome or new ST segment elevation
             or depression or new Q wave on ECG

          -  Corrected QT interval (QTc) > 480 msec

          -  Ongoing treatment with any drugs known to prolong the QTc interval, including
             anti-arrhythmic medications (stable regimen of antidepressants of the selective
             serotonin reuptake inhibitor (SSRI) class is allowed))

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  Significant vascular disease or recent peripheral arterial thrombosis

          -  Known intolerance of or hypersensitivity to fosbretabulin

          -  History of solid organ transplant or bone marrow transplant

          -  Any other intercurrent medical condition, including mental illness or substance abuse,
             deemed by the Investigator to be likely to interfere with a subject's ability to sign
             informed consent, cooperate and participate in the study, or interfere with the
             interpretation of the results

          -  High grade or poorly differentiated NET

          -  NET tumor other than PNET or GI-NET

          -  No elevated biomarker (>ULN) that can be followed

          -  Received regional hepatic infusion therapy within 6 months of enrollment (RFA allowed
             >6 months prior to enrollment)