Phase 2
N=22
Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors
Neuroendocrine Tumors
Bottom Line
View on ClinicalTrials.gov: NCT00605566 ↗Enrolled (actual)
22
Serious AEs
50.0%
Results posted
Feb 2019
Primary outcome: Primary: Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR). — 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Sorafenib (Drug); Cyclophosphamide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University Health Network, Toronto
- Primary completion
- Feb 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR). |
1 | — |
| PRIMARY Association Between p-Shift Changes and Treatment Efficacy of Individual Dose Adjustment of Sorafenib |
2.8; 14.9; 6.4; 21.3 | — |
| SECONDARY Progression-free Survival (PFS) |
3 | — |
| SECONDARY Overall Survival (OS) |
11.7 | — |
| SECONDARY 1-year Survival Rate |
45 | — |
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
Data sourced from ClinicalTrials.gov (NCT00605566). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.