Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors

This study has been completed.
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
First received: January 18, 2008
Last updated: March 14, 2016
Last verified: March 2016
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.

Condition Intervention Phase
Neuroendocrine Tumors
Drug: sorafenib and cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Tailored-dose Sorafenib Plus Metronomic Cyclophosphamide in Advanced Neuroendocrine Tumors (NET): a Phase II Clinical Trial Based on Individual Pharmacodynamic Assessment

Resource links provided by NLM:

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • 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. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the toxicity, time-to-progression (TTP), overall survival (OS), and 1 year survival rate. [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: January 2008
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
Patients will receive sorafenib and cyclophosphamide.
Drug: sorafenib and cyclophosphamide
During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of > 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.
Other Names:
  • BAY 43-9006
  • Cytoxan


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00605566

Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Principal Investigator: Lillian Siu, MD University Health Network, Toronto
  More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00605566     History of Changes
Other Study ID Numbers: SOR-NET-001 
Study First Received: January 18, 2008
Last Updated: March 14, 2016
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by University Health Network, Toronto:

Additional relevant MeSH terms:
Carcinoid Tumor
Neuroendocrine Tumors
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Physiological Effects of Drugs
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 22, 2016