NCT03014297

Fosbretabulin With Everolimus in Neuroendocrine Tumors With Progression

A Phase 1 Study of Fosbretabulin in Combination With Everolimus in Neuroendocrine Tumors (Grades 1-3) That Have Progressed After at Least One Prior Regimen for Metastatic Disease

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: Lowell Anthony, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single center, open label, phase I study involving grade I-III gastroenteropancreatic neuroendocrine tumors, consisting of a dose escalation Part A followed by an expansion cohort Part B. On Part A Patients will be treated with daily oral everolimus. Fosbretabulin will be administered IV either q3 weekly or q weekly based on PO CRM cohort. Part B: Once the investigators have established an MTD in Part A, the investigators will be treating 15 more patients at that dose combination. The primary and secondary objectives of the expansion cohort will be similar to Part A of the study, i.e., to establish a safety profile of the experimental drug combination and to collect and assess efficacy data. Patients will be treated with concurrent everolimus and fosbretabulin for 12 weeks.

Detailed description

A variety of treatment options are available for NETs with carcinoid syndrome including surgical and medical therapies. Most subjects require somatostatin analogs to control the symptoms of carcinoid syndrome. Subjects who no longer respond to somatostatin and other liver-directed therapies, who experience progression of disease and increasing symptoms have limited options, including participation in a clinical trial. Recently everolimus and sunitinib have been approved for the treatment of subjects with progressive locally advanced or metastatic neuroendocrine tumors. Based on the preclinical data in models of NETs and the clinical activity seen in NETS and other tumor types that have existing tumor vascculature, this study will examine the effectiveness of fosbretabulin given in combination with everolimus in subjects with GI-NETs and PNETs.The vasoconstrictive effect of fosbretabulin is potent, though short-lived (4-8 hours), with no cumulative adverse effect. Everolimus inhibits angiogenesis, slows tumor growth and has a prolonged half-life (30 hours). Combining these two agents with distinctly different mechanisms of action may improve tumor control without additional toxicities, and has the potential of reducing drug resistance.

Conditions

• Neuroendocrine Tumors
• Everolimus

Interventions

Type	Name	Description
DRUG	everolimus	everolimus
DRUG	fosbretabulin	fosbretabulin

Timeline

• Start date: 2017-03-06
• Primary completion: 2018-06-05
• Completion: 2018-11-16
• First posted: 2017-01-09
• Last updated: 2019-08-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study