Clinical trial NCT00605566: Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors
Official title: Tailored-dose Sorafenib Plus Metronomic Cyclophosphamide in Advanced Neuroendocrine Tumors (NET): a Phase II Clinical Trial Based on Individual Pharmacodynamic Assessment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Keywords: Neuroendocrine
sorafenib
cyclophosphamide
pharmacodynamic
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2008-01-31
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief 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.


Eligibility 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

Primary outcomes:
measure: Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR).
timeFrame: Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years
measure: Association Between p-Shift Changes and Treatment Efficacy of Individual Dose Adjustment of Sorafenib
timeFrame: Assessed from start of study treatment until death, assessed up to 7 years.
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years
measure: Overall Survival (OS)
timeFrame: Assessed from start of study treatment until death, assessed up to 7 years.
measure: 1-year Survival Rate
timeFrame: 1 year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Lillian Siu, MD
role: PRINCIPAL_INVESTIGATOR
References: