Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors
Information source: University Health Network, Toronto
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neuroendocrine Tumors
Intervention: sorafenib and cyclophosphamide (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: University Health Network, Toronto Official(s) and/or principal investigator(s): Lillian Siu, MD, Principal Investigator, Affiliation: University Health Network, Toronto
Summary
This is a phase II clinical trial to assess the efficacy of the combination of metronomic
cyclophosphamide and tailored sorafenib dosing in advanced, progressive NET. NET are highly
vascular tumors, and high VEGF expression has been correlated with worse clinical and
pathological characteristics as well as poor prognosis. A novel antiangiogenic approach
relies on targeting not only the endothelial cells but also rendering them more sensitive to
VEGFR blockade by achieving pericyte detachment. In this study, the dose of sorafenib will
be titrated up to a maximum of 800mg BID based on patients' toxicity and on a novel
pharmacodynamic assay that measures inhibition of molecular target(PDGFR) in patients'
peripheral blood mononuclear cells. Dual VEGFR targeting is achieved by administering
sorafenib plus metronomic low dose cyclophosphamide.
Clinical Details
Official title: Tailored-dose Sorafenib Plus Metronomic Cyclophosphamide in Advanced Neuroendocrine Tumors (NET): a Phase II Clinical Trial Based on Individual Pharmacodynamic Assessment
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Primary outcome: To determine the efficacy of combination sorafenib plus metronomic cyclophosphamide in advanced, progressive NET, as measured by the objective response rate (ORR), and to assess the feasibility of the individual dose adjustment of sorafenib.
Secondary outcome: To assess the toxicity, time-to-progression (TTP), overall survival (OS), and 1 year survival rate.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Histologically or cytologically confirmed neuroendocrine tumors
- Progressive and measurable metastatic disease
- Patients must not have disease that is currently amenable to surgery
- Life expectancy of greater than 3 months
- ECOG performance status ≤2
- Patients must have normal organ and marrow function
- Negative pregnancy test; agreement to use adequate birth control
Exclusion Criteria:
- Patients receiving chemotherapy or radiotherapy within last 4 weeks
- Patients that had received Sorafenib for advanced NET(neuroendocrine tumors) are
not allowed
- Any other investigational agents within 4 weeks of study
- Patients with known brain metastases
- History of allergic reactions to compounds of similar chemical/biologic composition
to sorafenib or cyclophosphamide
- Concurrent cancer from another primary site requiring treatment within the past 3
years
- Uncontrolled intercurrent illness
- Pregnant women and women who are breastfeeding
- HIV-positive patients receiving combination anti-retroviral therapy
Locations and Contacts
Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada
Additional Information
Starting date: January 2008
Last updated: June 5, 2012
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