a ph 2 study of fosbretabulin in subjects w pancreatic or gastrointestinal neuroendocrine tumors w elevated biomarkers

Conditions: Neuroendocrine Tumors

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.

subjects enrolled in this pnet/gi-net study (ox4218s) will receive weekly dosing with fosbretabulin for up to 3 cycles or approximately 9 weeks.

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)

Keywords: pnet gi-net neuroendocrine carcinoid